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  • 1.
    Acosta Ruiz, Vanessa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Dahlman, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Brekkan, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Microwave ablation of 105 T1 renal tumors: technique efficacy with a mean follow-up of two years2020In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 0, no 0, p. 1-8, article id 284185120956283Article in journal (Refereed)
    Abstract [en]

    Background: Thermal ablation (TA) with radiofrequency (RFA) or cryoablation (CA) are established treatments for small renal masses (≤4 cm). Microwave ablation (MWA) has several potential benefits (decreased ablation time, less susceptibility to heat-sink, higher lesion temperatures than RFA) but is still considered experimental considering the available small-sample studies with short follow-up.

    Purpose: To evaluate technique efficacy and complications of our initial experience of renal tumors treated using percutaneous MWA with a curative intent.

    Material and Methods: A total of 105 renal tumors (in 93 patients) were treated between April 2014 and August 2017. MWA was performed percutaneously with computed tomography (CT) guidance under conscious sedation (n=82) or full anesthesia. Patients were followed with contrast-enhanced CT scans at six months and yearly thereafter for a minimum of five years. The mean follow-up time was 2.1 years. The percentage of tumors completely ablated in a single session (primary efficacy rate) and those successfully treated after repeat ablation (secondary efficacy rate) were recorded. Patient and tumor characteristics as well as complications were collected retrospectively.

    Results: The median patient age was 70 years and median tumor size was 25 mm. Primary efficacy rate was 96.2% (101/105 tumors). After including two residual tumors for a second ablation session, secondary efficacy was 97.1% (102/105). Periprocedural complications were found in 5.2% (5/95) sessions: four Clavien-Dindo I and one Clavien-Dindo IIIa. One postprocedural Clavien-Dindo II complication was found.

    Conclusion: MWA has high efficacy rates and few complications compared to other TA methods at a mean follow-up of two years.

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  • 2.
    Acosta Ruiz, Vanessa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ladjevardi, Sam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Brekkan, Einar
    Uppsala University Hospital, Urology, Uppsala, Sweden.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Periprocedural outcome after laparoscopic partial nephrectomy versus radiofrequency ablation for T1 renal tumors: A modified R.E.N.A.L nephrometry score adjusted comparison2019In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 60, no 2, p. 260-268Article in journal (Refereed)
    Abstract [en]

    Background: Comparable oncological outcomes have been seen after surgical nephrectomy and thermal ablation of renal tumors recently. However, periprocedural outcome needs to be assessed for aiding treatment decision.

    Purpose: To compare efficacy rates and periprocedural outcome (technical success, session time, hospitalization time, and complications) after renal tumor treatment with laparoscopic partial nephrectomy (LPN) or radiofrequency ablation (RFA).

    Material and Methods: The initial experience with 49 (treated with LPN) and 84 (treated with RFA) consecutive patients for a single renal tumor (diameter ≤ 5 cm, limited to the kidney) during 2007-2014 was evaluated. Patient and tumor characteristics, efficacy rates, and periprocedural outcome were collected retrospectively. The stratified Mantel Haenzel and Van Elteren tests, adjusted for tumor complexity (with the modified R.E.N.A.L nephrometry score [m-RNS]), were used to assess differences in treatment outcomes.

    Results: Primary efficacy rate was 98% for LPN and 85.7% for RFA; secondary efficacy rate was 93.9% for LPN and 95.2% for RFA; and technical success rate was 87.8% for LPN and 100% for RFA. Median session (m-RNS adjusted P < 0.001; LPN 215 min, RFA 137 min) and median hospitalization time were longer after LPN (m-RNS adjusted P < 0.001; LPN 5 days, RFA 2 days). Side effects were uncommon (LPN 2%, RFA 4.8%). Complications were more frequent after LPN (m-RNS adjusted P < 0.001; LPN 42.9%, RFA 10.7%).

    Conclusion: Both methods achieved equivalent secondary efficacy rates. RFA included several treatment sessions, but session and hospitalization times were shorter, and complications were less frequent than for LPN. The differences remained after adjustment for renal tumor complexity.

  • 3.
    Acosta Ruiz, Vanessa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lönnemark, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Brekkan, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Dahlman, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Predictive factors for complete renal tumor ablation using RFA2016In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 57, no 7, p. 886-893Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Radiofrequency ablation (RFA) can be used to treat renal masses in patients where surgery is preferably avoided. As tumor size and location can affect ablation results, procedural planning needs to identify these factors to limit treatment to a single session and increase ablation success.

    PURPOSE: To identify factors that may affect the primary efficacy of complete renal tumor ablation with radiofrequency after a single session.

    MATERIAL AND METHODS: Percutaneous RFA (using an impedance based system) was performed using computed tomography (CT) guidance. Fifty-two renal tumors (in 44 patients) were retrospectively studied (median follow-up, 7 months). Data collection included patient demographics, tumor data (modified Renal Nephrometry Score, histopathological diagnosis), RFA treatment data (electrode placement), and follow-up results (tumor relapse). Data were analyzed through generalized estimating equations.

    RESULTS: Primary efficacy rate was 83%. Predictors for complete ablation were optimal electrode placement (P = 0.002, OR = 16.67) and increasing distance to the collecting system (P = 0.02, OR = 1.18). Tumor size was not a predictor for complete ablation (median size, 24 mm; P = 0.069, OR = 0.47), but all tumors ≤2 cm were completely ablated. All papillary tumors and oncocytomas were completely ablated in a single session; the most common incompletely ablated tumor type was clear cell carcinoma (6 of 9).

    CONCLUSION: Optimal electrode placement and a long distance from the collecting system are associated with an increased primary efficacy of renal tumor RFA. These variables need to be considered to increase primary ablation success. Further studies are needed to evaluate the effect of RFA on histopathologically different renal tumors.

  • 4.
    Adam, Meike
    et al.
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany.;Univ Tubingen, Dept Urol, Tubingen, Germany..
    Tennstedt, Pierre
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Lanwehr, Dominik
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Tilki, Derya
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany.;Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany..
    Steuber, Thomas
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Beyer, Burkhard
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Thederan, Imke
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Heinzer, Hans
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Haese, Alexander
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Salomon, Georg
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Budäus, Lars
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Michl, Uwe
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Pehrke, Dirk
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ Hosp, Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Bernard, Jürgen
    Fraunhofer Inst Graf Datenverarbeitung, Darmstadt, Germany..
    Klaus, Bernd
    Univ Med Ctr Hamburg Eppendorf, Dept Radiooncol, Hamburg, Germany..
    Pompe, Raisa S.
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Petersen, Cordula
    Univ Med Ctr Hamburg Eppendorf, Dept Radiooncol, Hamburg, Germany..
    Huland, Hartwig
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Graefen, Markus
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany..
    Schwarz, Rudolf
    Univ Med Ctr Hamburg Eppendorf, Dept Radiooncol, Hamburg, Germany..
    Huber, Wolfgang
    European Mol Biol Lab, Genome Biol Unit, Heidelberg, Germany..
    Loeb, Stacy
    NYU, Dept Urol, Populat Hlth, New York, NY 10003 USA.;NYU, Laura & Isaac Perlmutter Canc Ctr, New York, NY 10003 USA..
    Schlomm, Thorsten
    Univ Med Ctr Hamburg Eppendorf, Prostate Canc Ctr, Martini Klin, Martinistr 52, D-20246 Hamburg, Germany.;Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany..
    Functional Outcomes and Quality of Life After Radical Prostatectomy Only Versus a Combination of Prostatectomy with Radiation and Hormonal Therapy2017In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, no 3, p. 330-336Article in journal (Refereed)
    Abstract [en]

    Background: While the optimal use and timing of secondary therapy after radical prostatectomy (RP) remain controversial, there are limited data on patient-reported outcomes following multimodal therapy.

    Objective: To assess the impact of additional radiation therapy (RT) and/or androgen deprivation therapy (ADT) on urinary continence, potency, and quality of life (QoL) after RP.

    Design, setting, and participants: Among 13 150 men who underwent RP from 1992 to 2013, 905 received RP + RT, 407 RP + ADT and 688 RP + RT + ADT.

    Outcome measurements and statistical analyses: Urinary function, sexual function, and overall QoL were evaluated annually using self-administered validated questionnaires. Propensity score-matched and bootstrap analyses were performed, and the distributions for all functional outcomes were analyzed as a function of time after RP.

    Results and limitations: Patients who received RP + RT had a 4% higher overall incontinence rate 3 yr after surgery, and 1% higher rate for severe incontinence (> 3 pads/24 h) compared to matched RP-only patients. ADT further increased the overall and severe incontinence rates by 4% and 3%, respectively, compared to matched RP + RT patients. RP + RT was associated with an 18% lower rate of potency compared to RP alone, while RP + RT + ADT was associated with a further 17% reduction compared to RP + RT. Additional RT reduced QoL by 10% and additional ADT by a further 12% compared to RP only and RP + RT, respectively. The timing of RT after RP had no influence on continence, but adjuvant compared to salvage RT was associated with significantly lower potency (37% vs 45%), but higher QoL (60% vs 56%). Limitations of our study include the observational study design and potential for selection bias in the treatments received.

    Conclusions: Secondary RT and ADT after RP have an additive negative influence on urinary function, potency, and QoL. Patients with high-risk disease should be counseled before RP on the potential net impairment of functional outcomes due to multimodal treatment.

    Patient summary: Men with high-risk disease choosing surgery upfront should be counseled on the potential need for additional radiation and or androgen deprivation, and the potential net impairment of functional outcomes arising from multimodal treatment.

  • 5. Adami, Hans-Olov
    et al.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Johansson, Jan-Erik
    Radikal prostatektomi utvärderad: 18 års uppföljning i svensk randomiserad multicenterstudie2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 11, no 15, p. 682-683Article in journal (Other academic)
  • 6. Adami, Hans-Olov
    et al.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Johansson, Jan-Erik
    Management of Early Prostate Cancer REPLY2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 22, p. 2151-2151Article in journal (Refereed)
  • 7.
    Adamo, Hanibal
    et al.
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Hammarsten, Peter
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Hägglöf, Christina
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Scherdin, Tove Dahl
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Egevad, Lars
    Karolinska Univ Hosp, Dept Oncol Pathol, Stockholm, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Bergström, Sofia Halin
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Bergh, Anders
    Umea Univ, Dept Med Biosci, Pathol, 6M, Umea, Sweden.
    Prostate cancer induces C/EBP expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome2019In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, no 5, p. 435-445Article in journal (Refereed)
    Abstract [en]

    Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein- (C/EBP).

    Methods: To explore this further, we examined C/EBP expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.

    Results: In rats, C/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.

    Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.

  • 8.
    Ahlberg, Mats Steinholtz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Surveillance and follow-up of early prostate cancer2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Active surveillance (AS) for prostate cancer was introduced to address overtreatment resulting from prostate-specific antigen (PSA) testing. Despite advancements such as Magnetic Resonance Imaging (MRI) and targeted biopsies, PSA remains crucial in prostate cancer diagnostics, leading to ongoing challenges of overdiagnosis and overtreatment. This thesis aimed to investigate different aspects of AS and follow-up of early prostate cancer and provide new insights to reduce overtreatment and enhance surveillance and follow-up. In Paper I, the rationale and methodology of a randomized controlled trial, the Prostate Cancer Active Surveillance Trigger trial/Scandinavian Prostate Cancer Group study no. 17 (PCASTt/SPCG17), were outlined. This trial's objective is to evaluate the safety of an AS protocol based on MRI and standardized triggers for repeat biopsies and transition to radical treatment. Patient recruitment is anticipated to conclude in 2024. Paper II investigated the risks of biochemical recurrence, metastatic disease, and prostate cancer-related death in patients following radical prostatectomy. The analysis was conditioned on time after radical prostatectomy without biochemical recurrence. For patients with favourable histopathology in prostatectomy specimens and no biochemical recurrence five years post-prostatectomy, the probability of developing metastatic disease or dying from prostate cancer within 20 years after surgery was very low. This suggests shorter follow-up for selected patients. Paper III compared outcomes of AS for men from different healthcare regions in Sweden with varying traditions of AS. Regions with lower uptake in AS demonstrated a higher probability of transitioning from AS to radical treatment, but no difference in AS failure. The results suggest overtreatment in regions with low uptake in AS. Paper IV explored the associations between potential triggers for transitioning from AS to radical treatment and the transition to treatment. We analysed how this association changed with the introduction of prostate MRI. We found an increasingly strong association between triggers, particularly histopathological progression, and transition. However, most treated men had not experienced histopathological progression. The introduction of MRI did not contribute much to the change. In conclusion, this thesis outlines an ongoing study on defined triggers for transitioning from AS to radical treatment, suggests shorter follow-up after radical prostatectomy for selected patients, reveals overtreatment in regions with low uptake in AS, and shows an increasing use of histopathological progression as a trigger for transition to radical treatment.

    List of papers
    1. PCASTt/SPCG-17-a randomised trial of active surveillance in prostate cancer: rationale and design
    Open this publication in new window or tab >>PCASTt/SPCG-17-a randomised trial of active surveillance in prostate cancer: rationale and design
    Show others...
    2019 (English)In: BMJ Open, E-ISSN 2044-6055, Vol. 9, no 8Article in journal (Refereed) Published
    Abstract [en]

    Introduction Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. Methods and analysis A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, <= T2a, prostate-specific antigen (PSA) <15ng/mL, PSA density <less than or equal to>0.2ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled. Ethics and dissemination Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. Trial registration number NCT02914873.

    Place, publisher, year, edition, pages
    BMJ PUBLISHING GROUP, 2019
    Keywords
    active surveillance, MRI, prostate cancer, randomised trial
    National Category
    Urology and Nephrology
    Identifiers
    urn:nbn:se:uu:diva-401175 (URN)10.1136/bmjopen-2018-027860 (DOI)000502537200134 ()31444180 (PubMedID)
    Funder
    Swedish Cancer Society, 2016/466Swedish Cancer Society, 2014/1275Swedish Research Council, 2016-00177Swedish Research Council, 2016-01293
    Available from: 2020-01-07 Created: 2020-01-07 Last updated: 2023-12-06Bibliographically approved
    2. Time without PSA recurrence after radical prostatectomy as a predictor of future biochemical recurrence, metastatic disease and prostate cancer death: a prospective Scandinavian cohort study
    Open this publication in new window or tab >>Time without PSA recurrence after radical prostatectomy as a predictor of future biochemical recurrence, metastatic disease and prostate cancer death: a prospective Scandinavian cohort study
    Show others...
    2022 (English)In: BMJ Open, E-ISSN 2044-6055, Vol. 12, no 12, article id e057242Article in journal (Refereed) Published
    Abstract [en]

    Objective: Although surveillance after radical prostatectomy routinely includes repeated prostate specific antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be shortened for many patients without increasing the risk of prostate cancer death. We investigated the long-term probabilities of PSA recurrence, metastases and prostate cancer death in patients without biochemical recurrence five and 10 years after radical prostatectomy.

    Design: Prospective cohort study. Stratification by Gleason score (<= 3+4=7or >= 4+3=7), pathological tumour stage (pT2 or >= pT3) and negative or positive surgical margins.

    Setting: Between 1989 and 1998, 14 urological centres in Scandinavia randomised patients to the Scandinavian Prostate Cancer Group study number 4 (SPCG-4) trial.ParticipationAll 306 patients from the SPCG-4 trial who underwent radical prostatectomy within 1year from inclusion were eligible. Four patients were excluded due to surgery-related death (n=1) or salvage radiotherapy or hormonal treatment within 6weeks from surgery (n=3).

    Primary outcome measures: Cumulative incidences and absolute differences in metastatic disease and prostate cancer death.

    Results: We analysed 302 patients with complete follow-up during a median of 24 years. Median preoperative PSA was 9.8ng/mL and median age was 65 years. For patients without biochemical recurrence 5 years after radical prostatectomy the 20-year probability of biochemical recurrence was 25% among men with Gleason score <= 3+4=7and 57% among men with Gleason score >= 4+3=7; the probabilities for metastases were 0.8% and 17%; and for prostate cancer death 0.8% and 12%, respectively. The long-term probabilities were higher for pT >= 3versus pT2 and for positive versus negative surgical margins. Limitations include small size of the cohort.

    Conclusion: Many patients with favourable histopathology without biochemical recurrence 5years after radical prostatectomy could stop follow-up earlier than 10 years after radical prostatectomy.

    Place, publisher, year, edition, pages
    BMJ Publishing Group Ltd, 2022
    Keywords
    Prostate disease, Urological tumours, Epidemiology
    National Category
    Urology and Nephrology Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-497720 (URN)10.1136/bmjopen-2021-057242 (DOI)000924517900003 ()36581423 (PubMedID)
    Funder
    Swedish Cancer Society, 2016/466Swedish Cancer Society, 2014/1275Swedish Research Council, 2016-00177Swedish Research Council, 2016-01293ProstatacancerförbundetPercy Falks stiftelse för forskning beträffande prostatacancer och bröstcancer
    Available from: 2023-03-07 Created: 2023-03-07 Last updated: 2023-12-06Bibliographically approved
    3. Variations in the Uptake of Active Surveillance for Prostate Cancer and Its Impact on Outcomes
    Open this publication in new window or tab >>Variations in the Uptake of Active Surveillance for Prostate Cancer and Its Impact on Outcomes
    2023 (English)In: European Urology Open Science, ISSN 2666-1691, E-ISSN 2666-1683, Vol. 52, p. 166-173Article in journal (Refereed) Published
    Abstract [en]

    Background: Regional differences in active surveillance (AS) uptake for prostate cancer (PC) illustrate an inequality in treatment strategies.

    Objective: To examine the association between regional differences in AS uptake and transition to radical treatment, start of androgen deprivation therapy (ADT), watchful waiting, or death.

    Design, setting, and participants: A Swedish population-based cohort study was con-ducted including men in the National Prostate Cancer Register in Sweden with low -risk or favorable intermediate-risk PC, starting AS from January 1, 2007 and continuing till December 31, 2019.

    Intervention: Regional tradition of low, intermediate, or high proportions of immediate radical treatment. Outcomes measurements and statistical analysis:Probabilities of transition from AS to radical treatment, start of ADT, watchful waiting, or death from other causes were assessed.

    Results and limitations: We included 13 679 men. The median age was 66 yr, median PSA 5.1 ng/ml, and median follow-up 5.7 yr. Men from regions with a high AS uptake had a lower probability of transition to radical treatment (36%) than men from regions with a low AS uptake (40%; absolute difference 4.1%; 95% confidence interval [CI] 1.0-7.2), but not a higher probability of AS failure defined as the start of ADT (absolute difference 0.4%; 95% CI -0.7 to 1.4). There were no statistically significant differences in the probability of transition to watchful waiting or death from other causes. Limitations include uncertainty in the estimation of remaining lifetime and transition to watchful waiting.

    Conclusions:A regional tradition of a high AS uptake is associated with a lower probability of transition to radical treatment, but not with AS failure. A low AS uptake suggests overtreatment.

    Place, publisher, year, edition, pages
    Elsevier BV, 2023
    Keywords
    Active surveillance, Prostate cancer, Outcomes, Overtreatment
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-509996 (URN)10.1016/j.euros.2023.04.006 (DOI)001043792000001 ()37284040 (PubMedID)
    Funder
    Swedish Cancer Society, 190020ProstatacancerförbundetPercy Falks stiftelse för forskning beträffande prostatacancer och bröstcancerStiftelsen Hillevi Fries forskningsfond
    Available from: 2023-08-28 Created: 2023-08-28 Last updated: 2023-12-06Bibliographically approved
    4. Triggers for transition from active surveillance to radical treatment of prostate cancer 2008-2020 – a case control study
    Open this publication in new window or tab >>Triggers for transition from active surveillance to radical treatment of prostate cancer 2008-2020 – a case control study
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: What should trigger transition from active surveillance (AS) to radical treatment for prostate cancer (PC) remains an unanswered question. 

    Objective:To examine the association between potential triggers and transition from AS to radical treatment.Design, Setting and Participants:Swedish register-based case-control study including men in the National Prostate Cancer Register in Sweden with low- or favorable intermediate-risk PC, starting AS from Jan 1st, 2008, to Dec 31st, 2020.

    Interventions: Triggers are: histopathological progression, MRI progression without histopathological progression, and only PSA progression.

    Outcomes measurements and statistical analysis: Probability of experiencing a trigger one year preceding treatment. Odds ratios (OR) of histopathological progression, MRI progression without histopathological progression, or only PSA progression, for transition to radical treatment, analyzed by logistic regression.

    Results and limitations: The study base included 846 patients, 99 cases 2008-2014, and 172 cases 2015-2020. For every case, 10 controls were chosen. Histopathological progression was strongly associated with transition to radical treatment (OR 2008-2014: 6.89, 95% confidence interval (CI) 3.78-12.56; 2015-2020: 65.03, 95% CI 35.11-120.44). MRI progression was associated with treatment 2015-2020 (adjusted OR 4.01, 95% CI 1.72-9.36) but PSA progression was not associated with treatment in any adjusted analyses. Absence of any progression was strongly associated with reduced probability of transition to treatment (adjusted OR 2008-2014: 0.24, 95% CI 0.15-0.39, adjusted OR 2015-2020: 0.08, 95% CI 0.05-0.12) but the probability of treated men not having experienced any trigger was still 27% 2015-2020. Limitations include small study-base.

    Conclusion: Histopathological progression during AS was increasingly strongly associated with transition to treatment but the probability of not having experienced any trigger before treatment was 27%.

    Patient summary: Reliance on objective signs of progression before discontinuing AS increase, but still about a quarter of treated men have not experienced progression.

    Keywords
    Prostate cancer, Active surveillance, Triggers
    National Category
    Urology and Nephrology Cancer and Oncology
    Research subject
    Urology
    Identifiers
    urn:nbn:se:uu:diva-515871 (URN)
    Available from: 2023-11-13 Created: 2023-11-13 Last updated: 2023-12-06
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  • 9.
    Ahlberg, Mats Steinholtz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Triggers for transition from active surveillance to radical treatment of prostate cancer 2008-2020 – a case control studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background: What should trigger transition from active surveillance (AS) to radical treatment for prostate cancer (PC) remains an unanswered question. 

    Objective:To examine the association between potential triggers and transition from AS to radical treatment.Design, Setting and Participants:Swedish register-based case-control study including men in the National Prostate Cancer Register in Sweden with low- or favorable intermediate-risk PC, starting AS from Jan 1st, 2008, to Dec 31st, 2020.

    Interventions: Triggers are: histopathological progression, MRI progression without histopathological progression, and only PSA progression.

    Outcomes measurements and statistical analysis: Probability of experiencing a trigger one year preceding treatment. Odds ratios (OR) of histopathological progression, MRI progression without histopathological progression, or only PSA progression, for transition to radical treatment, analyzed by logistic regression.

    Results and limitations: The study base included 846 patients, 99 cases 2008-2014, and 172 cases 2015-2020. For every case, 10 controls were chosen. Histopathological progression was strongly associated with transition to radical treatment (OR 2008-2014: 6.89, 95% confidence interval (CI) 3.78-12.56; 2015-2020: 65.03, 95% CI 35.11-120.44). MRI progression was associated with treatment 2015-2020 (adjusted OR 4.01, 95% CI 1.72-9.36) but PSA progression was not associated with treatment in any adjusted analyses. Absence of any progression was strongly associated with reduced probability of transition to treatment (adjusted OR 2008-2014: 0.24, 95% CI 0.15-0.39, adjusted OR 2015-2020: 0.08, 95% CI 0.05-0.12) but the probability of treated men not having experienced any trigger was still 27% 2015-2020. Limitations include small study-base.

    Conclusion: Histopathological progression during AS was increasingly strongly associated with transition to treatment but the probability of not having experienced any trigger before treatment was 27%.

    Patient summary: Reliance on objective signs of progression before discontinuing AS increase, but still about a quarter of treated men have not experienced progression.

  • 10.
    Ahlberg, Mats Steinholtz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Adami, Hans-Olov
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
    Beckmann, Kerri
    Kings Coll London, Translat Oncol & Urol Res, London, England;Univ Southern Australia, Ctr Populat Hlth Res, Adelaide, SA, Australia.
    Bertilsson, Helena
    Univ Sykehuset Trondheim, Dept Urol, Sankt Olavs Hosp, Trondheim, Norway;NTNU Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, Trondheim, Norway.
    Bratt, Ola
    Goteborgs Univ Sahlgrenska Akad, Dept Urol, Gothenburg, Sweden.
    Cahill, Declan
    Royal Mardsen Hosp, London, England.
    Egevad, Lars
    Karolinska Univ Sjukhuset, Stockholm, Sweden.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Sch Canc & Pharmaceut Sci, London, England;.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Div Canc Studies, Sch Med, London, England.
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Rannikko, Antti
    Univ Helsinki, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Van Hemelrijck, Mieke
    Kings Coll London, Translat Oncol Off, London, England;Kings Coll London, Translat Urol Off, London, England.
    Jaderling, Fredrik
    Karolinska Univ Sjukhuset, Dept Radiol, Stockholm, Sweden;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Wassberg, Cecilia
    Karolinska Univ Sjukhuset, Dept Radiol, Stockholm, Sweden.
    Åberg, Ulrika W. N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    PCASTt/SPCG-17-a randomised trial of active surveillance in prostate cancer: rationale and design2019In: BMJ Open, E-ISSN 2044-6055, Vol. 9, no 8Article in journal (Refereed)
    Abstract [en]

    Introduction Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. Methods and analysis A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, <= T2a, prostate-specific antigen (PSA) <15ng/mL, PSA density <less than or equal to>0.2ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled. Ethics and dissemination Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. Trial registration number NCT02914873.

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  • 11.
    Ahlberg, Mats Steinholtz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Adami, Hans-Olov
    Univ Oslo, Inst Hlth & Soc, Clin Effectiveness Grp, Oslo, Norway.;Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Andren, Ove
    Örebro Univ, Fac Med & Hlth, Dept Urol, Örebro, Sweden..
    Johansson, Jan-Erik
    Örebro Univ, Fac Med & Hlth, Dept Urol, Örebro, Sweden..
    Steineck, Gunnar
    Univ Gothenburg, Inst Clin Sci, Dept Oncol, Div Clin Canc Epidemiol,Sahlgrenska Acad, Gothenburg, Sweden..
    Holmberg, Lars
    Kings Coll London, Sch Canc & Pharmaceut Sci, London, England..
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Time without PSA recurrence after radical prostatectomy as a predictor of future biochemical recurrence, metastatic disease and prostate cancer death: a prospective Scandinavian cohort study2022In: BMJ Open, E-ISSN 2044-6055, Vol. 12, no 12, article id e057242Article in journal (Refereed)
    Abstract [en]

    Objective: Although surveillance after radical prostatectomy routinely includes repeated prostate specific antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be shortened for many patients without increasing the risk of prostate cancer death. We investigated the long-term probabilities of PSA recurrence, metastases and prostate cancer death in patients without biochemical recurrence five and 10 years after radical prostatectomy.

    Design: Prospective cohort study. Stratification by Gleason score (<= 3+4=7or >= 4+3=7), pathological tumour stage (pT2 or >= pT3) and negative or positive surgical margins.

    Setting: Between 1989 and 1998, 14 urological centres in Scandinavia randomised patients to the Scandinavian Prostate Cancer Group study number 4 (SPCG-4) trial.ParticipationAll 306 patients from the SPCG-4 trial who underwent radical prostatectomy within 1year from inclusion were eligible. Four patients were excluded due to surgery-related death (n=1) or salvage radiotherapy or hormonal treatment within 6weeks from surgery (n=3).

    Primary outcome measures: Cumulative incidences and absolute differences in metastatic disease and prostate cancer death.

    Results: We analysed 302 patients with complete follow-up during a median of 24 years. Median preoperative PSA was 9.8ng/mL and median age was 65 years. For patients without biochemical recurrence 5 years after radical prostatectomy the 20-year probability of biochemical recurrence was 25% among men with Gleason score <= 3+4=7and 57% among men with Gleason score >= 4+3=7; the probabilities for metastases were 0.8% and 17%; and for prostate cancer death 0.8% and 12%, respectively. The long-term probabilities were higher for pT >= 3versus pT2 and for positive versus negative surgical margins. Limitations include small size of the cohort.

    Conclusion: Many patients with favourable histopathology without biochemical recurrence 5years after radical prostatectomy could stop follow-up earlier than 10 years after radical prostatectomy.

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  • 12.
    Ahlberg, Mats Steinholtz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala Univ Hosp, Dept Urol, Akad Sjukhuset Ing 70, S-75185 Uppsala, Sweden..
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala Univ Hosp, Reg Canc Ctr Uppsala Örebro, Uppsala, Sweden.;Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res TOUR, London, England..
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res TOUR, London, England..
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Variations in the Uptake of Active Surveillance for Prostate Cancer and Its Impact on Outcomes2023In: European Urology Open Science, ISSN 2666-1691, E-ISSN 2666-1683, Vol. 52, p. 166-173Article in journal (Refereed)
    Abstract [en]

    Background: Regional differences in active surveillance (AS) uptake for prostate cancer (PC) illustrate an inequality in treatment strategies.

    Objective: To examine the association between regional differences in AS uptake and transition to radical treatment, start of androgen deprivation therapy (ADT), watchful waiting, or death.

    Design, setting, and participants: A Swedish population-based cohort study was con-ducted including men in the National Prostate Cancer Register in Sweden with low -risk or favorable intermediate-risk PC, starting AS from January 1, 2007 and continuing till December 31, 2019.

    Intervention: Regional tradition of low, intermediate, or high proportions of immediate radical treatment. Outcomes measurements and statistical analysis:Probabilities of transition from AS to radical treatment, start of ADT, watchful waiting, or death from other causes were assessed.

    Results and limitations: We included 13 679 men. The median age was 66 yr, median PSA 5.1 ng/ml, and median follow-up 5.7 yr. Men from regions with a high AS uptake had a lower probability of transition to radical treatment (36%) than men from regions with a low AS uptake (40%; absolute difference 4.1%; 95% confidence interval [CI] 1.0-7.2), but not a higher probability of AS failure defined as the start of ADT (absolute difference 0.4%; 95% CI -0.7 to 1.4). There were no statistically significant differences in the probability of transition to watchful waiting or death from other causes. Limitations include uncertainty in the estimation of remaining lifetime and transition to watchful waiting.

    Conclusions:A regional tradition of a high AS uptake is associated with a lower probability of transition to radical treatment, but not with AS failure. A low AS uptake suggests overtreatment.

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  • 13.
    Ahlström, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Letocha, H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Andersson, J
    Institutionen för läkemedelskemi; Plattformen för preklinisk PET, Uppsala university, Uppsala.
    Långström, Bengt
    Institutionen för läkemedelskemi; Plattformen för preklinisk PET, Uppsala university, Uppsala.
    Nilsson, S
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Positron emission tomography in the diagnosis and staging of urinary bladder cancer1996In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 37, no 2, p. 180-185Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    Evaluation of positron emission tomography (PET) using (18)fl 18F-2-fluoro-2-deoxy-D-glucose (18FDG) and L-methyl-11C-methionine in the diagnosis and staging of urinary bladder carcinoma.

    MATERIAL AND METHODS:

    Twenty-three patients with biopsy-proven urinary bladder carcinoma were examined with PET after intravenous injection of 11C-methionine; 2 were also examined with 18FDG. The results from the PET investigations were compared with CT or MR findings and TNM classification before and after treatment.

    RESULTS:

    The urinary excretion of 18FDG prevented distinction of the primary tumour from the surrounding tracer. With 11C-methionine it was possible to detect 18/23 primary tumours. A trend was seen, suggesting that the higher the uptake values of 11C-methionine in the tumour, the greater the tumour stage.

    CONCLUSION:

    It is possible to visualize urinary bladder tumours larger than 1 cm in diameter with PET using (11)C-methionine, but the value of the method in the staging of the lesions is not superior to conventional methods.

  • 14. Aljabery, Firas
    et al.
    Liedberg, Fredrik
    Häggström, Christel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Department of Biobank Research, Umeå University; Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University.
    Ströck, Viveka
    Hosseini, Abolfazl
    Gårdmark, Truls
    Sherif, Amir
    Jerlström, Tomas
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Hagberg, Oskar
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Treatment and prognosis of patients with urinary bladder cancer with other primary cancers: a nationwide population-based study in the Bladder Cancer Data Base Sweden (BladderBaSe).2020In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 126, no 5, p. 625-632Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study how patients with urinary bladder cancer (UBC) with previous or concomitant other primary cancers (OPCs) were treated, and to investigate their prognosis.

    PATIENTS AND METHODS: Using nationwide population-based data in the Bladder Cancer Data Base Sweden (BladderBaSe), we analysed the probability of treatment with curative intent, and UBC-specific and overall survival (OS) in patients with UBC diagnosed in the period 1997-2014 with or without OPC. The analyses considered the patient's characteristics, UBC tumour stage at diagnosis, and site of OPC.

    RESULTS: There were 38 689 patients, of which 9804 (25%) had OPCs. Those with synchronous OPCs more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro-intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, Charlson Comorbidity Index and T-stage, UBC-specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis.

    CONCLUSIONS: OPC is common in patients with UBC. Treatment for UBC, after or in conjunction with an OPC, should not be neglected and carries just as high a probability of success as treatment in patients with UBC only. The needs of patients with UBC and OPC, and optimisation of their treatment considering their complicated disease trajectory are important areas of research.

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  • 15. Allen, Naomi E
    et al.
    Travis, Ruth C
    Appleby, Paul N
    Albanes, Demetrius
    Barnett, Matt J
    Black, Amanda
    Bueno-de-Mesquita, H Bas
    Deschasaux, Mélanie
    Galan, Pilar
    Goodman, Gary E
    Goodman, Phyllis J
    Gunter, Marc J
    Heliövaara, Markku
    Helzlsouer, Kathy J
    Henderson, Brian E
    Hercberg, Serge
    Knekt, Paul
    Kolonel, Laurence N
    Lasheras, Christina
    Linseisen, Jakob
    Metter, E Jeffrey
    Neuhouser, Marian L
    Olsen, Anja
    Pala, Valeria
    Platz, Elizabeth A
    Rissanen, Harri
    Reid, Mary E
    Schenk, Jeannette M
    Stampfer, Meir J
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Tangen, Catherine M
    Touvier, Mathilde
    Trichopoulou, Antonia
    van den Brandt, Piet A
    Key, Timothy J
    Selenium and Prostate Cancer: Analysis of Individual Participant Data From Fifteen Prospective Studies.2016In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 108, no 11Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade.

    METHODS: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided.

    RESULTS: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, Pheterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, Ptrend < .001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, Pheterogeneity = .08).

    CONCLUSIONS: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.

  • 16.
    Al-Mashhadi, Ammar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Ladjevardi, Sam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Paediatric Inflammation Research.
    Stenberg, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Persson, A. Erik G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlstrom, Mattias
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Changes of arterial pressure following relief of obstruction in adults with hydronephrosis2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 4, p. 216-224Article in journal (Refereed)
    Abstract [en]

    Background: As much as 20% of all cases of hypertension are associated with kidney malfunctions. We have previously demonstrated in animals and in pediatric patients that hydronephrosis causes hypertension, which was attenuated by surgical relief of the ureteropelvic junction (UPJ) obstruction. This retrospective cohort study aimed to investigate: (1) the proposed link between hydronephrosis, due to UPJ obstruction, and elevated arterial pressure in adults; and (2) if elevated blood pressure in patients with hydronephrosis might be another indication for surgery.

    Materials and methods: Medical records of 212 patients undergoing surgical management of hydronephrosis, due to UPJ obstruction, between 2000 and 2016 were assessed. After excluding patients with confounding conditions and treatments, paired arterial pressures (i.e. before/after surgery) were compared in 49 patients (35 years old; 95% CI 29–39). Split renal function was evaluated by using mercaptoacetyltriglycine (MAG3) renography before surgical management of the hydronephrotic kidney.

    Results: Systolic (−11 mmHg; 95% CI 6–15 mmHg), diastolic (−8 mmHg; 95% CI 4–11 mmHg), and mean arterial (-9 mmHg; 95% CI 6–12) pressures were significantly reduced after relief of the obstruction (p < 0.001). Split renal function of the hydronephrotic kidney was 39% (95% CI 37–41). No correlations were found between MAG3 and blood pressure level before surgery or between MAG3 and the reduction of blood pressure after surgical management of the UPJ obstruction.

    Conclusions: In adults with hydronephrosis, blood pressure was reduced following relief of the obstruction. Our findings suggest that elevated arterial pressure should be taken into account as an indication to surgically correct hydronephrosis.

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  • 17.
    Alvaeus, Julia
    et al.
    Umeå Univ, Dept Surg & Perioperat Sci, Urol & Androl, S-90185 Umeå, Sweden..
    Rosenblatt, Robert
    Umeå Univ, Dept Surg & Perioperat Sci, Urol & Androl, S-90185 Umeå, Sweden.;Stockholm South Gen Hosp, Dept Urology, Karolinska Inst, Stockholm, Sweden..
    Johansson, Markus
    Umeå Univ, Dept Surg & Perioperat Sci, Urol & Androl, S-90185 Umeå, Sweden.;Sundsvall Hosp, Dept Urol, Sundsvall, Sweden..
    Alamdari, Farhood
    Vastmanland Hosp, Dept Urol, Västerås, Sweden..
    Jakubczyk, Tomasz
    Lanssjukhuset Ryhov, Dept Urol, Jönköping, Sweden..
    Holmström, Benny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Hemdan, Tammer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Huge, Ylva
    Linköping Univ, Dept Clin & Expt Med, Div Urol, Linköping, Sweden..
    Aljabery, Firas
    Linköping Univ, Dept Clin & Expt Med, Div Urol, Linköping, Sweden..
    Gabrielsson, Susanne
    Karolinska Inst, Dept Med Solna, Div Immunol & Allergy, Stockholm, Sweden..
    Riklund, Katrine
    Umeå Univ, Dept Radiat Sci, Umeå, Sweden..
    Winqvist, Ola
    Karolinska Univ Hosp, Dept Clin Immunol, Stockholm, Sweden..
    Sherif, Amir
    Umeå Univ, Dept Surg & Perioperat Sci, Urol & Androl, S-90185 Umeå, Sweden..
    Fewer tumour draining sentinel nodes in patients with progressing muscle invasive bladder cancer, after neoadjuvant chemotherapy and radical cystectomy2020In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 38, no 9, p. 2207-2213Article in journal (Refereed)
    Abstract [en]

    Purpose

    To examine the relationship between the number of tumour draining sentinel nodes (SNs) and pathoanatomical outcomes, in muscle-invasive bladder cancer (MIBC), in patients undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC).

    Materials and Methods

    In an ongoing prospective multicenter study, we included 230 patients with suspected urothelial MIBC from ten Swedish urological centers. All underwent TURb and clinical staging. From the cohort, 116 patients with urothelial MIBC; cT2-cT4aN0M0, underwent radical cystectomy (RC) and lymphadenectomy with SN-detection (SNd). 83 patients received cisplatin-based NAC and 33 were NAC-naïve. The number and locations of detected SNs and non-SNs were recorded for each patient. The NAC treated patients were categorized by pathoanatomical outcomes post-RC into three groups: complete responders (CR), stable disease (SD) and progressive disease (PD). Selected covariates with possible impact on SN-yield were tested in uni -and multivariate analyses for NAC-treated patients only.

    Results

    In NAC treated patients, the mean number of SNs was significantly higher in CR patients (3.3) and SD patients (3.6) compared with PD patients (1.4) (p = 0.034). In a linear multivariate regression model, the number of harvested nodes was the only independent variable that affected the number of SNs (p = 0.0004).

    Conclusions

    The number of tumor-draining SNs in NAC-treated patients was significantly lower in patients with progressive disease.

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  • 18.
    Alverbratt, Charlotte
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Oncol, S-41396 Gothenburg, Sweden.
    Vikman, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Eriksson, Marie Hjalm
    St Goran Hosp, Dept Surg, Stockholm, Sweden.;Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Lissbrant, Ingela Franck
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Oncol, S-41396 Gothenburg, Sweden.
    Time difference in retrieving clinical information in Patient-overview Prostate Cancer compared to electronic health records2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 2, p. 95-101Article in journal (Refereed)
    Abstract [en]

    Background Patients with advanced prostate cancer (PCa) typically undergo numerous lines of treatment leading to large amounts of information in Electronic Health Records (EHRs). The Patient-overview Prostate Cancer (PPC) presents clinical information in a graphical overview. The aim of this study was to measure time spent on retrieving clinical information in PPC compared to EHRs, to assess if retrieved data was correct and to explore usability of PPC.

    Material and methods Oncologists, urologists and nurses in three hospitals in Sweden were timed when filling out questionnaires about patients using PPC and two different EHRs; Melior and COSMIC. Time and number of errors were analysed using linear mixed models (LMMs). Usability of PPC was measured with the System Usability Scale.

    Results The LMM showed a significantly shorter time to retrieve information in PPC compared to EHRs. The estimated time to complete one questionnaire was 8 minutes (95% CI = 6-10, p < 0.001) in PPC compared to 25 minutes in Melior and 21 minutes in COSMIC. Compared to PPC, the estimated time difference was 17 minutes longer in Melior (95% CI = 14-20, p < 0.001) and 13 minutes longer in COSMIC (95% CI = 10-17, p < 0.001). The LMM showed significantly fewer errors in PPC compared to Melior. No significant difference in the number of errors was found between PPC and COSMIC. The usability of PPC was rated as excellent by oncologists, urologists and nurses.

    Conclusion A graphical overview of a patient's medical history, as in PPC, gives health staff rapid access to relevant information with a high degree of usability.

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  • 19. Andersson, Gustav
    et al.
    Wennersten, Christoffer
    Gaber, Alexander
    Boman, Karolina
    Nodin, Bjorn
    Uhlen, Mathias
    Segersten, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Jirstrom, Karin
    Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival: validatory study of two independent patient cohorts2014In: BMC Urology, E-ISSN 1471-2490, Vol. 14, p. 36-Article in journal (Refereed)
    Abstract [en]

    Background: Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with tumour progression and poor prognosis in patients with T1G3 urothelial cell carcinoma of the bladder treated with non-maintenance Bacillus Calmette-Guerin (n = 92), and the associations with adverse clinicopathological factors have been validated in another, unselected, cohort (n = 104). In the present study, we examined the prognostic significance of ezrin expression in urothelial bladder cancer in a total number of 442 tumours from two independent patient cohorts. Methods: Immunohistochemical expression of ezrin was evaluated in tissue microarrays with tumours from one retrospective cohort of bladder cancer (n = 110; cohort I) and one population-based cohort (n = 342; cohort II). Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test and Cox regression proportional hazards' modeling were used to evaluate the impact of ezrin on 5-year overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS). Results: Ezrin expression could be evaluated in tumours from 100 and 342 cases, respectively. In both cohorts, reduced membranous ezrin expression was significantly associated with more advanced T-stage (p < 0.001), high grade tumours (p < 0.001), female sex (p = 0.040 and p = 0.013), and membranous expression of podocalyxin-like protein (p < 0.001 and p = 0.009). Moreover, reduced ezrin expression was associated with a significantly reduced 5-year OS in both cohorts (HR = 3.09 95% CI 1.71-5.58 and HR = 2.15(1.51-3.06), and with DSS in cohort II (HR = 2.77, 95% CI 1.78-4.31). This association also remained significant in adjusted analysis in Cohort I (HR1.99, 95% CI 1.05-3.77) but not in Cohort II. In pTa and pT1 tumours in cohort II, there was no significant association between ezrin expression and time to progression. Conclusions: The results from this study validate previous findings of reduced membranous ezrin expression in urothelial bladder cancer being associated with unfavourable clinicopathological characteristics and an impaired survival. The utility of ezrin as a prognostic biomarker in transurethral resection specimens merits further investigation.

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  • 20. Andersson, Lennart
    et al.
    Droller, Michael J.
    Adolfsson, Jan
    Månsson, Wiking
    Kirkali, Ziya
    Boffetta, Paolo
    Montironi, Rodolfo
    Malmström, Per-Uno
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Tribukait, Bernhard
    Grossman, H. Barton
    Chairmen's summary2008In: Scandinavian Journal of Urology and Nephrology, Supplementum, ISSN 0300-8886, E-ISSN 1651-2537, no 218, p. 7-11Article in journal (Refereed)
  • 21.
    Andersson, Marie
    et al.
    Helsingborg Hosp, Dept Urol, Charlotte Yhlensgata 10, S-25187 Helsingborg, Sweden..
    Berger, Marthe
    Lillebelt Hosp, Dept Urol, Vejle, Denmark..
    Zieger, Karsten
    Lillebelt Hosp, Dept Urol, Vejle, Denmark..
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Bläckberg, Mats
    Helsingborg Hosp, Dept Urol, Charlotte Yhlensgata 10, S-25187 Helsingborg, Sweden..
    The diagnostic challenge of suspicious or positive malignant urine cytology findings when cystoscopy findings are normal: an outpatient blue-light flexible cystoscopy may solve the problem2021In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 55, no 4, p. 263-267Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate whether outpatient blue-light flexible cystoscopy could solve the diagnostic challenge of positive or suspicious urine cytology findings despite normal white-light flexible cystoscopy results and normal findings on computerized tomography urography, in patients investigated for urothelial cancer.

    Material and methods: In a multicentre study, a total of 70 examinations were performed with the use of blue-light flexible cystoscopy (photodynamic diagnosis) after intravesical instillation of the fluorescence agent hexaminolevulinate. The examination started with a conventional white-light flexible cystoscopy and then the settings were switched to use blue light. Suspicious lesions were biopsied. Afterwards, the patients were interviewed regarding their experience of the examinations.

    Results: Bladder cancer was diagnosed in 29 out of 70 (41%) cases, among them 14/29 (48%) had malignant lesions seen only in blue light. The majority had carcinoma in situ (21/29). Normal findings were seen in 41 cases that underwent BLFC. During the further course, malignancy of the bladder was detected in six cases (9%) and malignancy of the upper urinary tract was detected in one case (1%). The majority of patients (93%) preferred the blue-light flexible cystoscopy performed at the outpatient clinic instead of the transurethral resection under general anaesthesia.

    Conclusion: Blue-light flexible cystoscopy at the outpatient clinic may be a useful tool to solve unclear cases of a malignant or suspicious urinary cytology suggestive of bladder cancer. The procedure was well tolerated by the patients.

  • 22. Armstrong, A J
    et al.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Stadler, W M
    Gingrich, J R
    Assikis, V
    Polikoff, J
    Damber, J E
    Belkoff, L
    Nordle, O
    Forsberg, G
    Carducci, M A
    Pili, R
    Long-term Survival and Biomarker Correlates of Tasquinimod Efficacy in a Multicenter Randomized Study of Men with Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer.2013In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 19, no 24, p. 6891-6901Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Tasquinimod (Active Biotech) is an oral immunomodulatory, anti-angiogenic, and anti-metastatic agent that delayed metastatic disease progression in a randomized placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). Here, we report long-term survival with biomarker correlates from this trial.

    EXPERIMENTAL DESIGN: Two hundred and one (134 tasquinimod and 67 placebo) men with mCRPC were evaluated. Forty-one men randomized to placebo crossed over to tasquinimod. Survival data were collected with a median follow-up time of 37 months. Exploratory biomarker studies at baseline and over time were collected to evaluate potential mechanism-based correlates with tasquinimod efficacy including progression-free survival (PFS) and overall survival (OS).

    RESULTS: With 111 mortality events, median OS was 33.4 months for tasquinimod versus 30.4 months for placebo overall, and 34.2 versus 27.1 months in men with bone metastases (n = 136), respectively. Multivariable analysis demonstrated an adjusted HR of 0.52 [95% confidence interval (CI), 0.35-0.78; P = 0.001] for PFS and 0.64 (95% CI, 0.42-0.97; P = 0.034) for OS, favoring tasquinimod. Time-to-symptomatic progression was improved with tasquinimod (P = 0.039, HR = 0.42). Toxicities tended to be mild in nature and improved over time. Biomarker analyses suggested a favorable impact on bone alkaline phosphatase and lactate dehydrogenase (LDH) over time and a transient induction of inflammatory biomarkers, VEGF-A, and thrombospondin-1 levels with tasquinimod. Baseline levels of thrombospondin-1 less than the median were predictive of treatment benefit.

    CONCLUSIONS: The survival observed in this trial of men with minimally symptomatic mCRPC suggests that the prolongation in PFS with tasquinimod may lead to a survival advantage in this setting, particularly among men with skeletal metastases, and has a favorable risk:benefit ratio. 

  • 23. Arnsrud Godtman, Rebecka
    et al.
    Månsson, Marianne
    Bratt, Ola
    Robinsson, David
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Kjölhede, Henrik
    Development and validation of a prediction model for identifying men with intermediate- or high-risk prostate cancer for whom bone imaging is unnecessary: a nation-wide population-based study2019In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 6, p. 378-384Article in journal (Refereed)
    Abstract [en]

    Objective: To develop and validate a nomogram that identifies men for whom bone scan is unnecessary.

    Material and methods: The study datasets were derived from the National Prostate Cancer Register (NPCR) of Sweden. All men in the NPCR ≤80 years of age who were diagnosed with intermediate- or high-risk prostate cancer and who had pretreatment bone imaging (99mTc MDP scintigraphy, plain x-ray, computed tomography, magnetic resonance imaging, and/or positron emission tomography fused with computed tomography) were included. Men diagnosed from 2015–2016 formed a development dataset and men diagnosed in 2017 formed a validation dataset. Outcome was metastasis on bone imaging as registered in NPCR. Multivariable logistic regression was used to develop a nomogram.

    Results: In the development dataset 482/5084 men (10%) had bone metastasis, the corresponding percentage in the validation dataset was 282/2554 (11%). Gleason grade group, clinical T stage, and prostate-specific antigen were included in the final model. Discrimination and calibration were satisfactory in both the development (AUC 0.80, 95% CI 0.78–0.82) and validation dataset (AUC 0.80, 95% CI, 0.77–0.82). Compared with using the EAU guidelines’ recommendation for selecting men for imaging, using the nomogram with a cut-off at 4% chance of bone metastasis, would have avoided imaging in 519/2068 men (25%) and miss bone metastasis in 10/519 (2%) men in the validation dataset.

    Conclusion: By use of our nomogram, bone scans of men with prostate cancer can be avoided in a large proportion of men.

  • 24.
    Arthur, R.
    et al.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
    Williams, R.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Malmstrom, H.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;Swedish Orphan Biovitrum, Stockholm, Sweden.
    Lambe, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Hammar, N.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;AstraZeneca, Global Med Dev Med Evidence & Observat Res, Stockholm, Sweden.
    Walldius, G.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Robinsson, D.
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Jungner, I.
    Karolinska Inst, Dept Clin Epidemiol, Stockholm, Sweden;CALAB Res, Stockholm, Sweden.
    Van Hemelrijck, M.
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Serum inflammatory markers in relation to prostate cancer severity and death in the Swedish AMORIS study2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 11, p. 2254-2262Article in journal (Refereed)
    Abstract [en]

    Inflammation is a well-documented driver of cancer development and progression. However, little is known about its role in prostate carcinogenesis. Thus, we examined the association of C-reactive protein (CRP), haptoglobin, albumin and white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk category and clinicopathological characteristics) and progression (defined by PCa death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure measurements taken approximately 14 years prior to diagnosis. We calculated odds ratio (OR) and 95% confidence interval (CI) for the associations between the inflammatory markers and PCa severity using logistic regression, while Cox proportional hazard regression was used for the associations with overall and PCa death. Serum CRP levels were associated with increased odds of high risk and metastatic PCa, and high PSA levels (20 mu g/L) (OR: 1.29; 95% CI: 1.06-1.56, 1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin levels were associated with increased odds of metastatic PCa, high PSA level and possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56, respectively). Albumin was positively associated with Gleason 4+3 tumour (1.38; 1.02-1.86) and overall death (HRunit increase in log: 1.60; 95% CI: 1.11-2.30), but inversely associated with high risk PCa and high PSA levels (20 mu g/L) (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of T3-T4 PCa. Except for albumin, none of these markers were associated with PCa death or overall death. Systemic inflammation as early as 14 years prior to diagnosis may influence prostate cancer severity. What's new? High levels of C-reactive protein can presage a particularly malignant prostate cancer, new results show. Cancers certainly arise in the wake of chronic inflammation, but it's not known exactly how markers of inflammation initiate prostate cancer. Here, the authors show that systemic inflammation can worsen the severity of the cancer, even if it occurred long before the cancer's onset. High levels of CRP and haptoglobin, they found, were associated with prostate cancer with high PSA and metastasis. The question remains whether inflammation pushes cancer cells into a more malignant mode, or selects for the more dangerous cells early on.

  • 25.
    Arthur, Rhonda
    et al.
    Kings Coll London, Canc Epidemiol Grp, Div Canc Studies, London, England..
    Møller, Henrik
    Kings Coll London, Canc Epidemiol Grp, Div Canc Studies, London, England..
    Garmo, Hans
    Kings Coll London, Canc Epidemiol Grp, Div Canc Studies, London, England.;Reg Canc Ctr, Uppsala, Sweden..
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Kings Coll London, Canc Epidemiol Grp, Div Canc Studies, London, England.;Reg Canc Ctr, Uppsala, Sweden..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Departments of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University.
    Malmstrom, Hakan
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden..
    Lambe, Mats
    Univ Uppsala Hosp, Dept Surg Sci, Uppsala, Sweden.;Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden.;Karolinska Inst, Dept Biostat, Stockholm, Sweden..
    Hammar, Niklas
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.;AstraZeneca Sverige, Sodertalje, Sweden..
    Walldius, Goran
    Karolinska Inst, Inst Environm Med, Dept Cardiovasc Epidemiol, Stockholm, Sweden..
    Robinson, David
    Departments of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University.
    Jungner, Ingmar
    Karolinska Inst, Dept Clin Epidemiol Unit, Stockholm, Sweden.;CALAB Res, Stockholm, Sweden..
    Van Hemelrijck, Mieke
    Kings Coll London, Canc Epidemiol Grp, Div Canc Studies, London, England.;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden..
    Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories2016In: Cancer Medicine, E-ISSN 2045-7634, Vol. 5, no 6, p. 1307-1318Article in journal (Refereed)
    Abstract [en]

    Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA<4 mu g/L, while those with glucose levels of 5.6-6.9 mmol/L had a greater odds of PSA>20 mu g/L compared to PSA 4.0-9.9 mu g/L. Hypertriglyceridemia was also positively associated with PSA>20 mu g/L. Hyperglycemic men had a greater odds of intermediate-and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention.

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  • 26.
    Arthur, Rhonda
    et al.
    Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY 10461 USA;Kings Coll London, Translat Oncol & Urol Res, London, England;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk, Bronx, NY 10461 USA.
    Møller, Henrik
    Kings Coll London, Translat Oncol & Urol Res, London, England.
    Garmo, Hans
    Kings Coll London, Translat Oncol & Urol Res, London, England;Uppsala Univ Hosp, Dept Surg Sci, Uppsala, Sweden.
    Häggström, Christel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Umea Univ, Dept Biobank Res, Umea, Sweden.
    Holmberg, Lars
    Kings Coll London, Translat Oncol & Urol Res, London, England.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Malmström, Håkan
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden;Swedish Orphan Biovitrum Sobi, Biostat Data Management & Med Writing, Res & Dev, Stockholm, Sweden.
    Lambe, Mats
    Uppsala Univ Hosp, Reg Canc Ctr, Uppsala, Sweden.
    Hammar, Niklas
    AstraZeneca, Med Evidence & Observat Res, Global Med Dev, Molndal, Sweden.
    Walldius, Göran
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Jungner, Ingmar
    Karolinska Inst, Dept Clin Epidemiol, Stockholm, Sweden;CALAB Res, Stockholm, Sweden.
    Van Hemelrijck, Mieke
    Kings Coll London, Translat Oncol & Urol Res, London, England.
    Serum glucose, triglycerides, and cholesterol in relation to prostate cancer death in the Swedish AMORIS study2019In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 30, no 2, p. 195-206Article in journal (Refereed)
    Abstract [en]

    Purpose: Lifestyle-related conditions such as obesity are associated with prostate cancer progression, but the associations with hyperglycemia and dyslipidemia are unclear. This study, therefore, aims to examine the association of glucose, triglycerides, and total cholesterol with prostate cancer death

    Methods: From the Swedish AMORIS cohort, we selected 14,150 men diagnosed with prostate cancer between 1996 and 2011 who had prediagnostic measurements of serum glucose, triglycerides, and total cholesterol. Multivariable Cox proportional hazards regressionmodels were used to determine the hazard ratios for death in relation to the aforementioned metabolic markers.

    Results: Using clinical cut-off points, a non-significant positive association was observed between glucose and prostate cancer death. When compared to those with glucose in the lowest quartile, those in the highest quartile had greater risk of prostate cancer death (HR 1.19; 95% CI 1.02-1.39). However, neither total cholesterol nor triglycerides were associated with prostate cancer death. Glucose and triglycerides were positively associated with overall, cardiovascular, and other deaths. Hypercholesterolemia was only associated with risk of CVD death.

    Conclusion: Our results suggest that glucose levels may influence prostate cancer survival, but further studies using repeated measurements are needed to further elucidate how glucose levels may influence prostate cancer progression.

  • 27.
    Assel, Melissa
    et al.
    Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Dahlin, Anders
    Lund University.
    Ulmert, David
    Lund Univerity; Molecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Bergh, Anders
    Umeå University.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umeå University.
    Lilja, Hans
    Lund University; University of Oxford; Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Vickers, Andrew J.
    Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
    Association Between Lead Time and Prostate Cancer Grade: Evidence of Grade Progression from Long-term Follow-up of Large Population-based Cohorts Not Subject to Prostate-specific Antigen Screening2018In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, no 6, p. 961-967Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Lead time (LT) is of key importance in early detection of cancer, but cannot be directly measured. We have previously provided LT estimates for prostate cancer (PCa) using archived blood samples from cohorts followed for many years without screening.

    OBJECTIVE: To determine the association between LT and PCa grade at diagnosis to provide an insight into whether grade progresses or is stable over time.

    DESIGN, SETTING, AND PARTICIPANTS: The setting was three long-term epidemiologic studies in Sweden including men not subject to prostate-specific antigen (PSA) screening. The cohort included 1041 men with PSA of 3-10 ng/ml at blood draw and subsequently diagnosed with PCa with grade data available.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic regression was used to predict high-grade (Gleason grade group ≥2 or World Health Organization grade 3) versus low-grade PCa at diagnosis in terms of LT, defined as the time between the date of elevated PSA and the date of PCa diagnosis with adjustment for cohort and age.

    RESULTS AND LIMITATIONS: The probability that PCa would be high grade at diagnosis increased with LT. Among all men combined, the risk of high-grade disease increased with LT (odds ratio 1.13, 95% confidence interval [CI] 1.10-1.16; p<0.0001), with no evidence of differences in effect by age group or cohort. Higher PSA predicted shorter LT by 0.46 yr (95% CI 0.28-0.64; p<0.0001) per 1 ng/ml increase in PSA. However, there was no interaction between PSA and grade, suggesting that the longer LT for high-grade tumors is not simply related to age. Limitations include the assumption that men with elevated PSA and subsequently diagnosed with PCa would have had biopsy-detectable PCa at the time of PSA elevation.

    CONCLUSIONS: Our data support grade progression, whereby following a prostate over time would reveal transitions from benign to low-grade and then high-grade PCa.

    PATIENT SUMMARY: Men with a longer lead time between elevated prostate-specific antigen and subsequent prostate cancer diagnosis were more likely to have high-grade cancers at diagnosis.

  • 28.
    Ax, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Garmo, Hans
    Regional Cancer Center , Uppsala University Hospital , Uppsala , Sweden.
    Grundmark, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Becker, Wulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Dietary Patterns and Prostate Cancer Risk: Report from the Population Based ULSAM Cohort Study of Swedish Men2014In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 66, no 1, p. 77-87Article in journal (Refereed)
    Abstract [en]

    Dietary pattern analyses have increased the possibilities to detect associations between diet and disease. However, studies on dietary pattern and prostate cancer are scarce. Food intake data in the Uppsala Longitudinal Study of Adult Men cohort was determined by 7-day food records. Adherence to a modified Mediterranean Diet Score (mMDS) and a low carbohydrate-high protein (LCHP) score were grouped as low, medium, or high in the whole study population (n = 1,044) and in those identified as adequate reporters of energy intake (n = 566), respectively. Prostate cancer risk was analyzed with Cox proportional hazard regression (median follow-up 13years) and competing risk of death was considered. There were no associations between dietary patterns and prostate cancer (n = 133) in the whole study population. Among adequate reporters the mMDS was not associated with prostate cancer (n = 72). The LCHP score was inversely related to prostate cancer in adequate reporters, adjusted hazard ratios; 0.55 (0.32-0.96) for medium and 0.47 (0.21-1.04) for high compared to low adherent participants (P-for-trend 0.04). Risk relations were not attributable to competing risk of death. In this study, a LCHP diet was associated with lower prostate cancer incidence. Relations emerged in adequate reporters, underscoring the importance of high-quality dietary data.

  • 29.
    Ax, Erika Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Grundmark, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Becker, Wulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Dietary Patterns and prostate cancer risk: a population based cohort study in elderly Swedish men2013In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 27, no S1, p. 847.8-Article in journal (Other academic)
  • 30.
    Axelson, Hans W
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Intraoperative Cavernous Nerve Stimulation and Laser-Doppler Flowmetry during Radical Prostatectomy2013In: Journal of Sexual Medicine, ISSN 1743-6095, E-ISSN 1743-6109, Vol. 10, no 11, p. 2842-2848Article in journal (Refereed)
    Abstract [en]

    Introduction. 

    Erectile dysfunction is a common side effect following radical prostatectomy mainly due to damage of the pelvic autonomic nerve fibers (cavernous nerves). Intraoperative electrical stimulation of the cavernous nerves while measuring changes in penile girth has previously been shown to provide the surgeon with feedback of nerve integrity.

    Aim. 

    To test the feasibility of recording changes in glans penis blood flow by Laser Doppler flowmetry from cavernous nerve stimulation.

    Methods. 

    Fifteen patients with localized prostate cancer undergoing radical prostatectomy had electrical stimulation of the proximal and distal parts of the neurovascular bundles after prostate removal. The stimulation consisted of 30-40 seconds biphasic constant current (10-30 mA) with 0.5 millisecond pulse duration.

    Main Outcome Measures. 

    Stimulus induced changes in penile blood flow was recorded from a Laser Doppler probe attached to the glans penis. Changes in penile girth were simultaneously recorded from a mercury-in rubber strain gauge. Erectile function was evaluated three months after surgery.

    Results. 

    Ten patients had stimulus induced increase in Laser Doppler flow unilaterally (N = 7) or bilaterally (N = 3). Out of 10 patients, 6 reported some preserved erectile function postoperatively at 3 months follow-up (indicating 6 true and 4 false positives). Three patients had no Doppler response from stimulation and had no postoperative erectile function postoperatively (indicating three true negatives). Two patients were excluded from the study due to bad signal quality in the Laser Doppler signal. In the majority of patients, stimulation produced increase in penile girth sensed by the strain gauge.

    Conclusion. 

    This preliminary report provides evidence that Laser Doppler Flowmetry is able to detect increased penile blood flow from intraoperative electrical stimulation of the neurovascular bundles. However, further improvement in the recording technique is required. Laser Doppler Flowmetry may also be feasible to confirm autonomic nerve sparing in women undergoing pelvic surgery.

  • 31.
    Balabanova, Yanina
    et al.
    Bayer AG, Integrated Evidence Generat, Berlin, Germany..
    Farahmand, Bahman
    Bayer AB, Integrated Evidence Generat, Stockholm, Sweden..
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Brobert, Gunnar
    Bayer AB, Integrated Evidence Generat, Stockholm, Sweden..
    Risk of venous thromboembolism in men with prostate cancer compared with men in the general population: a nationwide population-based cohort study in Sweden2022In: BMJ Open, E-ISSN 2044-6055, Vol. 12, no 5, article id e055485Article in journal (Refereed)
    Abstract [en]

    Objective

    To estimate the additional risk of venous thromboembolism (VTE) in men with prostate cancer compared with men without prostate cancer in Sweden.

    Design

    Nationwide cohort study following 92 105 men with prostate cancer and 466 241 men without prostate cancer (comparison cohort) matched 5:1 by birth year and residential region.

    Setting

    The male general population of Sweden (using the Nationwide Prostate Cancer data Base Sweden).

    Primary and secondary outcome measures

    Crude incidence proportion ratios (IPRs) comparing the incidence of VTE in men with prostate cancer and men in the comparison cohort. Cox regression was used to calculate HRs for VTE adjusted for confounders.

    Results

    2955 men with prostate cancer and 9774 men in the comparison cohort experienced a first VTE during a median of 4.5 years' follow-up. Deep vein thrombosis (DVT) accounted for 52% of VTE cases in both cohorts. Median time from start of follow-up to VTE was 2.5 years (IQR 0.9-4.7) in the prostate cancer cohort and 2.9 years (IQR 1.3-5.0) in the comparison cohort. Crude incidence rates of VTE per 1000 person-years were 6.54 (95% CI 6.31 to 6.78) in the prostate cancer cohort (n=2955 events) and 4.27 (95% CI 4.18 to 4.35) in the comparison cohort (n=9774 events). The IPR decreased from 2.53 (95% CI 2.26 to 2.83) at 6 months to 1.59 (95% CI 1.52 to 1.67) at 5 years' follow-up. Adjusted HRs were 1.48 (95% CI 1.39 to 1.57) for DVT and 1.47 (95% CI 1.39 to 1.56) for pulmonary embolism after adjustment for patient characteristics.

    Conclusions

    Swedish men with prostate cancer had a mean 50% increased risk of VTE during the 5 years following their cancer diagnosis compared with matched men free of prostate cancer. Physicians should be mindful of this marked increase in VTE risk in men with prostate cancer to help ensure timely diagnosis.

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  • 32.
    Balabanova, Yanina
    et al.
    Bayer AG, Integrated Evidence Generat, D-13353 Berlin, Germany..
    Farahmand, Bahman
    Bayer AB, Integrated Evidence Generat, Stockholm, Sweden..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Brobert, Gunnar
    Bayer AB, Integrated Evidence Generat, Stockholm, Sweden..
    Population-based study of long-term anticoagulation for treatment and secondary prophylaxis of venous thromboembolism in men with prostate cancer in Sweden2022In: BMC Urology, E-ISSN 1471-2490, Vol. 22, no 1, article id 15Article in journal (Refereed)
    Abstract [en]

    Background

    Epidemiological data on anticoagulation for venous thromboembolism (VTE) in prostate cancer are sparse. We aimed to investigate associations between anticoagulation duration and risks of VTE recurrence after treatment cessation and major on-treatment bleeding in men with prostate cancer in Sweden.

    Methods

    Using nationwide prostate cancer registry and prescribing data, we followed 1413 men with VTE and an outpatient anticoagulant prescription following prostate cancer diagnosis. Men were followed to identify cases of recurrent VTE, and hospitalized major bleeding. We calculated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) to quantify the association between anticoagulation duration (reference <= 3 months) and recurrent VTE using Cox regression. We estimated 1-year cumulative incidences of major bleedings from anticoagulation initiation.

    Results

    The outpatient anticoagulation prescribed was parenteral (64%), direct oral anticoagulant (31%), and vitamin K antagonist (20%). Median duration of anticoagulation was 7 months. Adjusted HRs (95% CI) for off-treatment recurrent pulmonary embolism (PE) were 0.32 (0.09-1.15) for > 3-6 months' duration, 0.21 (0.06-0.69) for > 6-9 months and 0.16 (0.05-0.55) for > 9 months; corresponding HRs for deep vein thrombosis (DVT) were 0.67 (0.27-1.66), 0.80 (0.31-2.07), and 1.19 (0.47-3.02). One-year cumulative incidences of intracranial, gastrointestinal and urogenital bleeding were 0.9%, 1.7%, 3.0% during treatment, and 1.2%, 0.9%, 1.6% after treatment cessation.

    Conclusion

    The greatest possible benefit in reducing recurrent VTE risk occurred with > 9 months anticoagulation for PE and > 3-6 months for DVT, but larger studies are needed to confirm this. Risks of major bleeding were low overall.

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  • 33.
    Beckmann, Kerri
    et al.
    Univ South Australia, Australian Ctr Precis Hlth, Adelaide, SA, Australia;Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Uppsala Univ Hosp, Reg Canc Ctr Uppsala, Uppsala, Sweden.
    Adolfsson, Jan
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Bosco, Cecilia
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Holmberg, Lars
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer2019In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, no 4, p. 676-683Article in journal (Refereed)
    Abstract [en]

    Background: Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.

    Objective: To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study.

    Design, setting, and participants: Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n = 2078) or GnRH agonists (n = 4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5 yr before through to 5 yr after starting androgen deprivation therapy (ADT).

    Outcome measures and statistical methods: Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses.

    Results and limitations: Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p < 0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20-144).

    Conclusions: Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment.

    Patient summary: Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy.

  • 34.
    Beckmann, Kerri
    et al.
    Univ South Australia, Allied Hlth & Human Performance, Canc Epidemiol & Populat Hlth Res Grp, Adelaide, SA 5001, Australia; Kings Coll London, Sch Canc & Pharmaceut Studies, Translat Oncol & Urol Res, London SE1 9RT, England.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Studies, Translat Oncol & Urol Res, London SE1 9RT, England; Uppsala Univ Hosp, Reg Canc Ctr, SE-75122 Uppsala, Sweden.
    Franck Lissbrant, Ingela
    Sahlgrenska Univ, Inst Clin Sci, Dept Oncol, SE-41345 Gothenburg, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    The Value of Real-World Data in Understanding Prostate Cancer Risk and Improving Clinical Care: Examples from Swedish Registries2021In: Cancers, ISSN 2072-6694, Vol. 13, no 4, article id 875Article, review/survey (Refereed)
    Abstract [en]

    Simple Summary

    Real-world data (RWD), i.e., data reflecting normal clinical practice collected outside the constraints of randomised controlled trials, provide important insights into our understanding of prostate cancer and its management. Clinical cancer registries are an important source of RWD. Depending on their scope and the potential linkage to other data sources, registry-based data can be utilised to address a variety of questions including risk factors, healthcare utilisation, treatment effectiveness, adverse effects, disparities in healthcare access, quality of care and healthcare economics. This review describes the various registry-based RWD sources for prostate cancer research in Sweden (namely the National Prostate Cancer Register, the Prostate Cancer data Base Sweden (PCBaSe) and the Patient-overview Prostate Cancer) and documents their utility for better understanding prostate cancer aetiology and improving clinical care.

    Abstract

    Real-world data (RWD), that is, data from sources other than controlled clinical trials, play an increasingly important role in medical research. The development of quality clinical registers, increasing access to administrative data sources, growing computing power and data linkage capacities have contributed to greater availability of RWD. Evidence derived from RWD increases our understanding of prostate cancer (PCa) aetiology, natural history and effective management. While randomised controlled trials offer the best level of evidence for establishing the efficacy of medical interventions and making causal inferences, studies using RWD offer complementary evidence about the effectiveness, long-term outcomes and safety of interventions in real-world settings. RWD provide the only means of addressing questions about risk factors and exposures that cannot be “controlled”, or when assessing rare outcomes. This review provides examples of the value of RWD for generating evidence about PCa, focusing on studies using data from a quality clinical register, namely the National Prostate Cancer Register (NPCR) Sweden, with longitudinal data on advanced PCa in Patient-overview Prostate Cancer (PPC) and data linkages to other sources in Prostate Cancer data Base Sweden (PCBaSe).

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  • 35.
    Beckmann, Kerri
    et al.
    Kings Coll London, Sch Canc & Pharmaceut Studies, TOUR, London, England.;Univ South Australia, Canc Res Inst, Adelaide, SA, Australia..
    Garmo, Hans
    Uppsala Univ Hosp, Reg Canc Ctr Uppsala, Uppsala, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Adolfsson, Jan
    Karolinska Inst, CLINTEC Dept, Stockholm, Sweden..
    Cruickshank, J. Kennedy
    Kings Coll London, Sch Life Course Sci, Dept Nutr Studies, London, England..
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Studies, TOUR, London, England.;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden..
    Spironolactone use is associated with lower prostate cancer risk: a population-wide case-control study2020In: Prostate Cancer and Prostatic Diseases, ISSN 1365-7852, E-ISSN 1476-5608, Vol. 23, no 3, p. 527-533Article in journal (Refereed)
    Abstract [en]

    Background Spironolactone, a cheap effective diuretic used to manage hypertension and heart failure, also has anti-androgenic effects through its non-selective binding to steroid receptors, and hence may affect prostate cancer (PCa) risk. This study investigated the association between spironolactone use and PCa risk. For comparison, we also examined associations with thiazide diuretics which do not have anti-androgenic properties. Methods A matched case-control study was undertaken using population-wide data from the Prostate Cancer Data Base Sweden (PCBaSe). All PCa cases diagnosed from 2014 to 2016 were matched by birth year and county with PCa-free controls selected from the general population (1:5). Multivariable conditional logistic regression was used to examine associations between spironolactone use (dose and duration) and PCa risk, and similarly for thiazides. Results Three percent of the 31,591 cases and 4% of the 156,802 controls had been prescribed spironolactone. Multivariable analyses indicated reduced risk of PCa among those ever exposed to spironolactone (odds ratio [OR] 0.83; 95% confidence interval [CI]: 0.76-0.89), with a stronger association for current users (OR: 0.77, 95% CI: 0.69-0.86) than past users (OR: 0.88; 95% CI: 0.79-0.97) and decreasing risk with increasing dose (p-trend < 0.001). No association was observed for thiazide exposure and PCa risk. Biases due to differences in prescribing patterns or frequency of PSA testing may have influenced these findings. Conclusion PCa risk was reduced among men exposed to the diuretic spironolactone. Further investigation of spironolactone's potential chemopreventive effects is warranted.

  • 36.
    Beckmann, Kerri
    et al.
    Kings Coll London, Sch Canc & Pharmaceut Studies, TOUR, London, England.;Univ South Australia, Canc Res Inst, Adelaide, SA, Australia..
    Garmo, Hans
    Uppsala Univ Hosp, Reg Canc Ctr Uppsala, Uppsala, Sweden..
    Nilsson, Per
    Skane Univ Hosp, Dept Oncol & Radiat Phys, Lund, Sweden.;Lund Univ, Lund, Sweden..
    Franck Lissbrant, Ingela
    Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden..
    Widmark, Anders
    Umeå Univ, Dept Radiat Sci, Umeå, Sweden..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Radical radiotherapy for prostate cancer: patterns of care in Sweden 1998-20162020In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 59, no 5, p. 549-557Article in journal (Refereed)
    Abstract [en]

    Introduction: Radiotherapy is an established treatment option for prostate cancer (PCa), both as primary treatment and secondary treatment after radical prostatectomy (RP). Since 1998, detailed data on radiotherapy delivered to Swedish men with PCa (e.g. treatment modalities, absorbed doses, fractionation) have been collated within PCa data Base Sweden (PCBaSe). This study reports patterns of radical radiotherapy for PCa in Sweden over the past two decades. Materials and methods: All men with non-metastatic PCa (1998-2016) who received external beam radiotherapy (EBRT) or high or low dose-rate brachytherapy (HDR-BT/LDR-BT) were identified in PCBaSe. Analyses included: trends in radiation techniques, fractionation patterns and total doses over time; PCa-specific survival comparing treatment in 2007-2017 with 1998-2006; and regional variation in type of primary radiotherapy. Results: About 20,876 men underwent primary radiotherapy. The main treatment modalities include conventionally fractionated (2.0 Gy/fraction) EBRT (51%), EBRT with HDR-BT boost (27%) and hypofractionated (>2.4 Gy/fraction) EBRT (11%). EBRT with photon or proton boost and HDR-BT and LDR-BT monotherapies were each used minimally. Use of dose-escalated EBRT (>74 Gy) and moderate hypofractionation increased over time, while use of HDR-BT declined. Considerable regional variation in treatment modalities was apparent. Risk of PCa death following primary radiotherapy had declined for intermediate-risk (HR: 0.60; 95%CI 0.47-0.87) and high-risk PCa (HR: 0.72; 95%CI 0.61-0.86). Discussion: Increased use of dose escalation and hypofractionated EBRT has occurred in Sweden over the past two decades, reflecting current evidence and practice guidelines. Disease-specific outcomes have also improved. Data collected in PCBaSe provide an excellent resource for further research into RT use in PCa management.

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  • 37.
    Beckmann, Kerri
    et al.
    Univ South Australia, UniSA Canc Res Inst, Adelaide, SA, Australia;Kings Coll London, Sch Canc & Pharmaceut Studies Translat Oncol, Sch Canc & Pharmaceut Studies, TOUR, London, England.
    Russell, Beth
    Kings Coll London, Sch Canc & Pharmaceut Studies Translat Oncol, Sch Canc & Pharmaceut Studies, TOUR, London, England.
    Josephs, Debra
    Kings Coll London, Sch Canc & Pharmaceut Studies Translat Oncol, Sch Canc & Pharmaceut Studies, TOUR, London, England.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Studies Translat Oncol, Sch Canc & Pharmaceut Studies, TOUR, London, England;Uppsala Univ Hosp, Reg Canc Ctr Uppsala, Uppsala, Sweden.
    Häggström, Christel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Umea Univ, Dept Biobank Res, Umea, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Sch Canc & Pharmaceut Studies Translat Oncol, Sch Canc & Pharmaceut Studies, TOUR, London, England.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Studies Translat Oncol, Sch Canc & Pharmaceut Studies, TOUR, London, England;Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Adolfsson, Jan
    Karolinska Inst, CLINTEC Dept, Stockholm, Sweden.
    Chronic inflammatory diseases, anti-inflammatory medications and risk of prostate cancer: a population-based case-control study2019In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, article id 612Article in journal (Refereed)
    Abstract [en]

    Background: Whether chronic inflammation increases prostate cancer risk remains unclear. This study investigated whether chronic inflammatory diseases (CID) or anti-inflammatory medication use (AIM) were associated with prostate cancer risk.

    Methods: Fifty-five thousand nine hundred thirty-seven cases (all prostate cancer, 2007-2012) and 279,618 age-matched controls were selected from the Prostate Cancer Database Sweden. CIDs and AIMs was determined from national patient and drug registers. Associations were investigated using conditional logistic regression, including for disease/drug subtypes and exposure length/dose.

    Results: Men with a history of any CID had slightly increased risk of any prostate cancer diagnosis (OR: 1.08; 95%CI: 1.04-1.12) but not unfavourable' (high-risk or advanced) prostate cancer. Generally, risk of prostate cancer was highest for shorter exposure times. However, a positive association was observed for asthma >5years before prostate cancer diagnosis (OR: 1.21; 95%CI: 1.05-1.40). Risk of prostate cancer was increased with prior use of any AIMs (OR: 1.26; 95%CI: 1.24-1.29). A positive trend with increasing cumulative dose was only observed for inhaled glucocorticoids (p<0.011).

    Conclusion: Detection bias most likely explains the elevated risk of prostate cancer with prior history of CIDs or use of AIMs, given the higher risk immediately after first CID event and lack of dose response. However, findings for length of time with asthma and dose of inhaled glucocorticoids suggest that asthma may increase risk of prostate cancer through other pathways.

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  • 38.
    Bergengren, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Quality of life aspects of being diagnosed and living with prostate cancer2021Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Prostate cancer is largely a heterogenous disease, ranging from almost harmless to highly aggressive. Most men are diagnosed with favorable-risk disease with a long life expectancy even without treatment. The risk of overdiagnosing and overtreating these men is substantial, with reduced quality of life as a result. In this thesis, we study the diagnostics of, and the quality of life for men with prostate cancer. 

    In paper I, we studied satisfaction with care among men with low-risk prostate cancer in a nationwide, population-based setting and found a high overall satisfaction with care. Information and participation in decision-making were of great importance for satisfaction. However, men on active surveillance reported lower overall satisfaction with care, suggesting that they need more information and to be more participatory in their care.

    In paper II, we investigated choice and adherence to active surveillance and found that a doctor’s recommendation was the most important factor for choosing active surveillance as the primary treatment strategy. A rising PSA was the most common cause for diverting from active surveillance to curative treatment, even though PSA alone is a poor marker for disease progression.

    In paper III, we explored lifestyle changes after a prostate cancer diagnosis and a possible association between lifestyle changes and quality of life. We found that a considerable proportion of men change their lifestyle after a prostate cancer diagnosis and that a positive lifestyle change was associated with a higher quality of life. However, men with poorer functional outcomes after treatment were less likely to make lifestyle changes, suggesting that these men need better support and rehabilitation.

    In paper IV, we used a new simulation model to evaluate the benefit and harm of the increased PSA-driven diagnostic activity that has occurred over the last 30 years. We found that the increased diagnostic activity has resulted in a modest decrease in prostate cancer specific mortality but at the cost of substantial overdiagnosis and overtreatment.

    To conclude, this thesis provides information on factors to improve satisfaction with care, increase adherence to active surveillance, and to engage in positive lifestyle changes, possibly contributing to a higher quality of life.

    List of papers
    1. Satisfaction with Care Among Men with Localised Prostate Cancer: A Nationwide Population-based Study
    Open this publication in new window or tab >>Satisfaction with Care Among Men with Localised Prostate Cancer: A Nationwide Population-based Study
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    2018 (English)In: European Urology Oncology, E-ISSN 2588-9311, Vol. 1, no 1, p. 37-45Article in journal (Refereed) Published
    Abstract [en]

    Background

    Information about how men with prostate cancer (PC) experience their medical care and factors associated with their overall satisfaction with care (OSC) is limited.

    Objective

    To investigate OSC and factors associated with OSC among men with low-risk PC.

    Design, setting, and participants

    Men registered in the National Prostate Cancer Register of Sweden as diagnosed in 2008 with low-risk PC at the age of ≤70 yr who had undergone radical prostatectomy (RP), radiotherapy (RT), or started on active surveillance (AS) were invited in 2015 to participate in this nationwide population-based survey (n = 1720).

    Outcome measurements and statistical analysis

    OSC data were analysed using ordinal logistic regression. Odds ratios (ORs) were calculated for comparisons between the highest and lowest possible response categories.

    Results and limitations

    A total of 1288 men (74.9%) responded. High OSC was reported by 958 (74.4%). Factors associated with high OSC were high participation in decision-making (OR 4.18, 95% confidence interval [CI] 2.61–6.69), receiving more information (OR 11.1, 95% CI 7.97–15.6), high-quality information (OR 7.85, 95% CI 5.46–11.3), access to a nurse navigator (OR 1.80, 95% CI 1.44–2.26), and better functional outcomes (defined as 25 points higher on the EPIC-26 questionnaire; OR 1.34, 95% CI 1.21–1.48). OSC was not affected by whether a doctor or specialist nurse conducted follow-up (OR 0.84, 95% CI 0.66–1.07). These findings were similar across treatment groups. Men who had undergone RP or RT reported high OSC more often than men on AS (78.2% vs 84.0% vs 72.6%), high participation in decision-making (70.5% vs 64.5% vs 49.2%), and having received more information (40.5% vs 45.8% vs 28.6%), and were less likely to believe they would die from PC (3.8% vs 3.9% vs 8.0%). Limitations include the nonrandomised retrospective design and potential recall bias.

    Conclusions

    Information and participation in decision-making, as well as access to a nurse navigator, are key factors for OSC, regardless of treatment. Men on AS need more information about their treatment and need to participate more in decision-making. OSC was as high among men who had nurse-led follow-up as among men who had doctor-led follow-up.

    Patient summary

    Information about how men with low-risk prostate cancer experience their medical care is limited. In this nationwide population-based study we found that information and participation in decision-making as well as access to a nurse navigator are key factors for satisfaction regardless of treatment. Men who are being closely watched for prostate cancer without immediate curative treatment need more information than they now receive and need to participate more in decision-making than they currently do.

    Keywords
    Information, Low-risk prostate cancer, Nurse-navigator, Participation in decision-making, Satisfaction
    National Category
    Urology and Nephrology
    Identifiers
    urn:nbn:se:uu:diva-381228 (URN)10.1016/j.euo.2018.02.003 (DOI)000474512200006 ()
    Funder
    Swedish Cancer Society
    Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2023-08-25Bibliographically approved
    2. Determinants for choosing and adhering to active surveillance for localised prostate cancer: a nationwide population-based study
    Open this publication in new window or tab >>Determinants for choosing and adhering to active surveillance for localised prostate cancer: a nationwide population-based study
    Show others...
    2019 (English)In: BMJ Open, E-ISSN 2044-6055, Vol. 9, no 12, article id e033944Article in journal (Refereed) Published
    Abstract [en]

    Objective: Knowledge about factors influencing choice of and adherence to active surveillance (AS) for prostate cancer (PC) is scarce. We aim to identify which factors most affected choosing and adhering to AS and to quantify their relative importance.

    Design, setting and participants; In 2015, we sent a questionnaire to all Swedish men aged <= 70 years registered in the National Prostate Cancer Register of Sweden who were diagnosed in 2008 with low-risk PC and had undergone prostatectomy, radiotherapy or started on AS.

    Outcome measurements and statistical analysis: Logistic regression was used to calculate ORs with 95% CIs for factors potentially affecting choice and adherence to AS.

    Results: 1288 out of 1720 men (75%) responded, 451 (35%) chose AS and 837 (65%) underwent curative treatment. Of those starting on AS, 238 (53%) diverted to treatment within 7 years. Most men (83%) choose AS because 'My doctor recommended AS'. Factors associated with choosing AS over treatment were older age (OR 1.81, 95% CI 1.29 to 2.54), a Charlson Comorbidity Index >2 (OR 1.50, 95% CI 1.06 to 2.13), being unaccompanied when notified of the cancer diagnosis (OR 1.45, 95% CI 1.11 to 1.89). Men with a higher prostate-specific antigen (PSA) at the time of diagnosis were less likely to adhere to AS (OR 0.26, 95% CI 0.10 to 0.63). The reason for having treatment after initial AS was 'the PSA level was rising' in 55% and biopsy findings in 36%.

    Conclusions: A doctors recommendation strongly affects which treatment is chosen for men with low-risk PC. Rising PSA values were the main factor for initiating treatment for men on AS. These findings need be considered by healthcare providers who wish to increase the uptake of and adherence to AS.

    Place, publisher, year, edition, pages
    BMJ PUBLISHING GROUP, 2019
    National Category
    Urology and Nephrology Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-407279 (URN)10.1136/bmjopen-2019-033944 (DOI)000512773400283 ()31874896 (PubMedID)
    Funder
    Swedish Cancer Society
    Available from: 2020-03-23 Created: 2020-03-23 Last updated: 2023-08-28Bibliographically approved
    3. Changes in lifestyle among prostate cancer survivors: A nationwide population-based study
    Open this publication in new window or tab >>Changes in lifestyle among prostate cancer survivors: A nationwide population-based study
    Show others...
    2020 (English)In: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 29, no 10, p. 1713-1719Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: Long-term information on lifestyle changes among prostate survivors is lacking. In this nationwide, population-based study we investigated the prevalence of lifestyle changes, factors associated with lifestyle changes and associations between lifestyle changes and general quality of life.

    METHODS: All men registered in the National Prostate Cancer Register of Sweden diagnosed in 2008 with low-risk prostate cancer at age 70 years or younger were sent a questionnaire. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals for factors potentially associated with lifestyle change.

    RESULTS: Out of 1288, 1720 men (75%) were responded. A total of 279 (22%) reported a positive lifestyle change regarding diet or exercise. Poor functional outcomes after treatment was associated with exercising less (OR 1.6, 95% CI 1.2-2.1) and less interest in social activities and relationships (OR 1.8, 95% CI 1.5-2.1). Men who exercised more (OR 7.9, 95% CI 4.4-14) and men who had an increased interest in relationships and social activities (OR 5.2, 95% CI 2.1-13) reported higher general quality of life.

    CONCLUSIONS: A considerable proportion of men reported making positive lifestyle changes after the prostate cancer diagnosis. The time after diagnosis may be a teachable moment that facilitates lifestyle interventions. Poor functional outcomes after treatment may reduce the willingness to engage in positive lifestyle change, which need be considered when supporting men after treatment. Men who made a positive lifestyle change, regardless of whether it was exercise or regarding relationships and social activities more often reported a high level of general quality of life.

    Keywords
    cancer, lifestyle, oncology, prostate cancer, psycho-oncology, quality of life, survivorship
    National Category
    Urology and Nephrology Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-425458 (URN)10.1002/pon.5513 (DOI)000564284200001 ()32779258 (PubMedID)
    Funder
    Swedish Cancer Society
    Available from: 2020-11-16 Created: 2020-11-16 Last updated: 2020-12-07Bibliographically approved
    4. The benefit and harm of prostate specific antigen driven diagnostic activity, a 20-year nationwide population-based evaluation
    Open this publication in new window or tab >>The benefit and harm of prostate specific antigen driven diagnostic activity, a 20-year nationwide population-based evaluation
    (English)In: Article in journal (Refereed) Submitted
    National Category
    Urology and Nephrology
    Identifiers
    urn:nbn:se:uu:diva-427316 (URN)
    Available from: 2020-12-07 Created: 2020-12-07 Last updated: 2020-12-07
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  • 39.
    Bergengren, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    The benefit and harm of prostate specific antigen driven diagnostic activity, a 20-year nationwide population-based evaluationIn: Article in journal (Refereed)
  • 40.
    Bergengren, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Belozerov, Alexej
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Garmo, Hans
    Uppsala Univ Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Hagberg, Oskar
    Lund Univ, Inst Translat Med, Malmö, Sweden..
    Aljabery, Firas
    Linköping Univ, Dept Clin & Expt Med, Div Urol, Linköping, Sweden..
    Gårdmark, Truls
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden..
    Jahnson, Staffan
    Linköping Univ, Dept Clin & Expt Med, Div Urol, Linköping, Sweden..
    Jerlström, Tomas
    Örebro Univ, Fac Med & Hlth, Sch Med Sci, Dept Urol, Örebro, Sweden..
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Sherif, Amir
    Umeå Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umeå, Sweden..
    Ströck, Viveka
    Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden.;Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden..
    Söderkvist, Karin
    Umeå Univ, Dept Radiat Sci Oncol, Umeå, Sweden..
    Ullén, Anders
    Karolinska Inst, Genitourinary Oncol & Urol Unit, Dept Oncol Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Pelv Canc, Stockholm, Sweden..
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Sch Canc & Pharmaceut Sci, London, England..
    Häggström, Christel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Umeå Univ, Northern Registry Ctr, Dept Publ Hlth & Clin Med, Umeå, Sweden..
    Liedberg, Fredrik
    Lund Univ, Inst Translat Med, Malmö, Sweden.;Skane Univ Hosp, Dept Urol, Malmö, Sweden..
    Short term outcomes after robot assisted and open cystectomy- A nation-wide population-based study2023In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 49, no 4, p. 868-874Article in journal (Refereed)
    Abstract [en]

    Introduction: We aimed to compare short term outcomes after robot assisted radical cystectomy (RARC) and open radical cystectomy (ORC) for urinary bladder cancer in a large population.

    Materials and methods: We included all patients without distant metastases who underwent either RARC or ORC with ileal conduit between 2011 and 2019 registered in the Bladder cancer data Base Sweden (BladderBaSe) 2.0. Primary outcome was unplanned readmissions within 90 days, and secondary out-comes within 90 days of surgery were reoperations, Clavien 3-5 complications, total days alive and out of hospital, and mortality. The analysis was carried out using multivariate regression models.

    Results: Out of 2905 patients, 832 were operated with RARC and 2073 with ORC. Robotic procedures were to a larger extent performed during later years, at high volume centers (47% vs 17%), more often for organ-confined disease (82% vs. 72%) and more frequently in patients with high socioeconomic status (26% vs. 21%). Patients operated with RARC were more commonly readmitted (29% vs. 25%). In multi -variable analysis RARC was associated with decreased risk of Clavien 3-5 complications (OR 0.58, 95% CI 0.47-0.72), reoperations (OR 0.53, 95% CI 0.39-0.71) and had more days alive and out of hospital (mean difference 3.7 days, 95% CI 2.4-5.0).

    Conclusion: This study illustrates the "real-world" effects of a gradual and nation-wide introduction of RARC. Patients operated with RARC had fewer major complications and reoperations but were more frequently readmitted compared to ORC. The observed differences were largely due to more wound related complications among patients treated with ORC.

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  • 41.
    Bergengren, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Enblad, Anna Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Bratt, Ola
    Univ Gothenburg, Sahlgrenska Acad, Dept Urol, Gothenburg, Sweden; Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Changes in lifestyle among prostate cancer survivors: A nationwide population-based study2020In: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 29, no 10, p. 1713-1719Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Long-term information on lifestyle changes among prostate survivors is lacking. In this nationwide, population-based study we investigated the prevalence of lifestyle changes, factors associated with lifestyle changes and associations between lifestyle changes and general quality of life.

    METHODS: All men registered in the National Prostate Cancer Register of Sweden diagnosed in 2008 with low-risk prostate cancer at age 70 years or younger were sent a questionnaire. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals for factors potentially associated with lifestyle change.

    RESULTS: Out of 1288, 1720 men (75%) were responded. A total of 279 (22%) reported a positive lifestyle change regarding diet or exercise. Poor functional outcomes after treatment was associated with exercising less (OR 1.6, 95% CI 1.2-2.1) and less interest in social activities and relationships (OR 1.8, 95% CI 1.5-2.1). Men who exercised more (OR 7.9, 95% CI 4.4-14) and men who had an increased interest in relationships and social activities (OR 5.2, 95% CI 2.1-13) reported higher general quality of life.

    CONCLUSIONS: A considerable proportion of men reported making positive lifestyle changes after the prostate cancer diagnosis. The time after diagnosis may be a teachable moment that facilitates lifestyle interventions. Poor functional outcomes after treatment may reduce the willingness to engage in positive lifestyle change, which need be considered when supporting men after treatment. Men who made a positive lifestyle change, regardless of whether it was exercise or regarding relationships and social activities more often reported a high level of general quality of life.

    Download full text (pdf)
    fulltext
  • 42.
    Bergengren, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Garmo, Hans
    Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden.
    Bratt, Ola
    Sahlgrens Acad, Dept Urol, Gothenburg, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Determinants for choosing and adhering to active surveillance for localised prostate cancer: a nationwide population-based study2019In: BMJ Open, E-ISSN 2044-6055, Vol. 9, no 12, article id e033944Article in journal (Refereed)
    Abstract [en]

    Objective: Knowledge about factors influencing choice of and adherence to active surveillance (AS) for prostate cancer (PC) is scarce. We aim to identify which factors most affected choosing and adhering to AS and to quantify their relative importance.

    Design, setting and participants; In 2015, we sent a questionnaire to all Swedish men aged <= 70 years registered in the National Prostate Cancer Register of Sweden who were diagnosed in 2008 with low-risk PC and had undergone prostatectomy, radiotherapy or started on AS.

    Outcome measurements and statistical analysis: Logistic regression was used to calculate ORs with 95% CIs for factors potentially affecting choice and adherence to AS.

    Results: 1288 out of 1720 men (75%) responded, 451 (35%) chose AS and 837 (65%) underwent curative treatment. Of those starting on AS, 238 (53%) diverted to treatment within 7 years. Most men (83%) choose AS because 'My doctor recommended AS'. Factors associated with choosing AS over treatment were older age (OR 1.81, 95% CI 1.29 to 2.54), a Charlson Comorbidity Index >2 (OR 1.50, 95% CI 1.06 to 2.13), being unaccompanied when notified of the cancer diagnosis (OR 1.45, 95% CI 1.11 to 1.89). Men with a higher prostate-specific antigen (PSA) at the time of diagnosis were less likely to adhere to AS (OR 0.26, 95% CI 0.10 to 0.63). The reason for having treatment after initial AS was 'the PSA level was rising' in 55% and biopsy findings in 36%.

    Conclusions: A doctors recommendation strongly affects which treatment is chosen for men with low-risk PC. Rising PSA values were the main factor for initiating treatment for men on AS. These findings need be considered by healthcare providers who wish to increase the uptake of and adherence to AS.

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  • 43.
    Bergengren, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Garmo, Hans
    Bratt, Ola
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Satisfaction with Care Among Men with Localised Prostate Cancer: A Nationwide Population-based Study2018In: European Urology Oncology, E-ISSN 2588-9311, Vol. 1, no 1, p. 37-45Article in journal (Refereed)
    Abstract [en]

    Background

    Information about how men with prostate cancer (PC) experience their medical care and factors associated with their overall satisfaction with care (OSC) is limited.

    Objective

    To investigate OSC and factors associated with OSC among men with low-risk PC.

    Design, setting, and participants

    Men registered in the National Prostate Cancer Register of Sweden as diagnosed in 2008 with low-risk PC at the age of ≤70 yr who had undergone radical prostatectomy (RP), radiotherapy (RT), or started on active surveillance (AS) were invited in 2015 to participate in this nationwide population-based survey (n = 1720).

    Outcome measurements and statistical analysis

    OSC data were analysed using ordinal logistic regression. Odds ratios (ORs) were calculated for comparisons between the highest and lowest possible response categories.

    Results and limitations

    A total of 1288 men (74.9%) responded. High OSC was reported by 958 (74.4%). Factors associated with high OSC were high participation in decision-making (OR 4.18, 95% confidence interval [CI] 2.61–6.69), receiving more information (OR 11.1, 95% CI 7.97–15.6), high-quality information (OR 7.85, 95% CI 5.46–11.3), access to a nurse navigator (OR 1.80, 95% CI 1.44–2.26), and better functional outcomes (defined as 25 points higher on the EPIC-26 questionnaire; OR 1.34, 95% CI 1.21–1.48). OSC was not affected by whether a doctor or specialist nurse conducted follow-up (OR 0.84, 95% CI 0.66–1.07). These findings were similar across treatment groups. Men who had undergone RP or RT reported high OSC more often than men on AS (78.2% vs 84.0% vs 72.6%), high participation in decision-making (70.5% vs 64.5% vs 49.2%), and having received more information (40.5% vs 45.8% vs 28.6%), and were less likely to believe they would die from PC (3.8% vs 3.9% vs 8.0%). Limitations include the nonrandomised retrospective design and potential recall bias.

    Conclusions

    Information and participation in decision-making, as well as access to a nurse navigator, are key factors for OSC, regardless of treatment. Men on AS need more information about their treatment and need to participate more in decision-making. OSC was as high among men who had nurse-led follow-up as among men who had doctor-led follow-up.

    Patient summary

    Information about how men with low-risk prostate cancer experience their medical care is limited. In this nationwide population-based study we found that information and participation in decision-making as well as access to a nurse navigator are key factors for satisfaction regardless of treatment. Men who are being closely watched for prostate cancer without immediate curative treatment need more information than they now receive and need to participate more in decision-making than they currently do.

  • 44.
    Bergengren, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Kaihola, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Borgefeldt, Ann-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Garmo, Hans
    Uppsala Univ Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Satisfaction with Nurse-led Follow-up in Prostate Cancer Patients-A Nationwide Population-based Study2022In: European Urology Open Science, ISSN 2666-1691, E-ISSN 2666-1683, Vol. 38, p. 25-31Article in journal (Refereed)
    Abstract [en]

    Background: Satisfaction with nurse-led follow-up among men with prostate can-cer is high. However, it is unclear whether all men are satisfied or whether there are men who would benefit from being followed by a urologist or a nurse.

    Objective: To investigate the follow-up distribution between urologists and nurses, and whether the high self-reported satisfaction with nurse-led follow-up is inde-pendent of other factors such as age or comorbidity.

    Design, setting, and participants: All Swedish men, <= 70 yr of age, with a low-risk prostate cancer diagnosis in 2008, answered a questionnaire 7 yr after diagnosis. The extensive questionnaire included a question on satisfaction with care, answered on a seven-point scale. Participants were divided based on whether they were followed up by a nurse, a urologist, or both.

    Outcome measurements and statistical analysis: Factors that could influence the level of satisfaction were identified as age, edu-cation, comorbidity, treatment, disease progression, urinary bother, level of infor-mation, and participation in treatment decision. Likelihood ratio tests from ordinal regression were used to test the null hypothesis of similar satisfaction between groups.

    Results and limitations: Out of 1288 men, 1137 (88%) answered both the question on who performed the follow-up and the question regarding satisfaction. In all, 350 men reported that they were followed up by nurses (31%), 598 (52%) by urologists, and 189 (17%) by both. No differences in satisfaction where seen between the groups. Approximately 50% were satisfied completely, regardless of who performed the follow-up. Results were not affected by age, educational level, comorbidity, treatment, disease progression, urinary bother, information, or participation in treatment decision. Limitations include the nonrandomized, retrospective design and a potential recall bias.

    Conclusions: Satisfaction with nurse-led follow-up is high, regardless of factors such as age, level of education, comorbidity, and treatment.

    Patient summary: Men with prostate cancer can be offered nurse-led follow-up on a regular basis and still maintain their satisfaction with health care.

    Download full text (pdf)
    fulltext
  • 45.
    Bergengren, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10065 USA..
    Pekala, Kelly R.
    Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10065 USA..
    Matsoukas, Konstantina
    Mem Sloan Kettering Canc Ctr, Med Lib, New York, NY USA..
    Fainberg, Jonathan
    Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10065 USA..
    Mungovan, Sean F.
    Westmead Private Hosp, Westmead Private Physiotherapy Serv & Clin Res Ins, Sydney, Australia..
    Bratt, Ola
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Urol, Gothenburg, Sweden..
    Bray, Freddie
    Int Agcy Res Canc, Canc Surveillance Branch, Lyon, France..
    Brawley, Otis
    Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA.;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA..
    Luckenbaugh, Amy N.
    Vanderbilt Univ, Med Ctr, Nashville, TN USA..
    Mucci, Lorelei
    Harvard TH Chan Sch Publ Hlth, Boston, MA USA..
    Morgan, Todd M.
    Univ Michigan, Dept Urol, Ann Arbor, MI USA..
    Carlsson, Sigrid, V
    Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10065 USA.;Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Urol, Gothenburg, Sweden.;Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA..
    2022 Update on Prostate Cancer Epidemiology and Risk Factors-A Systematic Review2023In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 84, no 2, p. 191-206Article, review/survey (Refereed)
    Abstract [en]

    Context: Prostate cancer (PCa) is one of the most common cancers worldwide. Understanding the epidemiology and risk factors of the disease is paramount to improve primary and secondary prevention strategies.

    Objective: To systematically review and summarize the current evidence on the descrip-tive epidemiology, large screening studies, diagnostic techniques, and risk factors of PCa.

    Evidence acquisition: PCa incidence and mortality rates for 2020 were obtained from the GLOBOCAN database of the International Agency for Research on Cancer. A systematic search was performed in July 2022 using PubMed/MEDLINE and EMBASE biomedical databases. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and was registered in PROSPERO (CRD42022359728).

    Evidence synthesis: Globally, PCa is the second most common cancer, with the highest incidence in North and South America, Europe, Australia, and the Caribbean. Risk factors include age, family history, and genetic predisposition. Additional factors may include smoking, diet, physical activity, specific medications, and occupational factors. As PCa screening has become more accepted, newer approaches such as magnetic resonance imaging (MRI) and biomarkers have been implemented to identify patients who are likely to harbor significant tumors. Limitations of this review include the evidence being derived from meta-analyses of mostly retrospective studies.

    Conclusions: PCa remains the second most common cancer among men worldwide. PCa screening is gaining acceptance and will likely reduce PCa mortality at the cost of over-diagnosis and overtreatment. Increasing use of MRI and biomarkers for the detection of PCa may mitigate some of the negative consequences of screening.

  • 46.
    Bergengren, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Westerberg, Marcus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Watch out for sticky diagnosis bias in older men with prostate cancer: Editorial comment to “Evidence of overestimating prostate cancer mortality in Estonia: a population-based study by Innos K et al.”2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 5-6, p. 365-366Article in journal (Refereed)
  • 47.
    Bergengren, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Westerberg, Marcus
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Applied Mathematics and Statistics.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res TOUR, London, England..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res TOUR, London, England.;Reg Canc Ctr Uppsala Örebro, Uppsala, Sweden..
    Variation in Prostate-Specific Antigen Testing Rates and Prostate Cancer Treatments and Outcomes in a National 20-Year Cohort2021In: JAMA Network Open, E-ISSN 2574-3805, Vol. 4, no 5, article id e219444Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: The diagnostic activity for prostate cancer has increased during the past decades. However, the benefit and harm of the increased diagnostic activity have not been quantified in detail for a country or a large region.

    OBJECTIVE: The aim of this study was to evaluate and quantify the association between increases in diagnostic activity driven by prostate-specific antigen testing and incidence of prostate cancer diagnosis, treatment, and mortality.

    DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the Proxy-Based Risk-Stratified Incidence Simulation Model-Prostate Cancer to examine observed data on all Swedish men with prevalent prostate cancer and compare them with a corresponding, hypothetical, simulated scenario with more restrictive diagnostic activity. All men aged 40 to 100 years living in Sweden during the time period 1996 to 2016 with incident and prevalent prostate cancer were included. The second scenario is the corresponding, hypothetical, simulated scenario where diagnostic activity remained constant as of 1996 (the beginning of the prostate-specific antigen testing era) throughout the study period.

    EXPOSURES: High or low diagnostic activity for prostate cancer.

    MAIN OUTCOMES AND MEASURES: Incidence of prostate cancer diagnosis, treatment (deferred treatment, curative treatment, and hormonal treatment), and prostate cancer mortality.

    RESULTS: During the study period from 1996 to 2016, 188 884 men were diagnosed with prostate cancer at a median (interquartile range) age of 71 (64-77) years. Compared with the low-diagnostic activity scenario, in the high-diagnostic activity scenario, the number of men diagnosed with prostate cancer was 48% higher (423 vs 286 [95% CI, 271-302] per 100 000 men per year), 148% more men were diagnosed with low- or intermediate-risk cancer (221 vs 89 [95% CI, 73-105] per 100 000 men per year), and 108% more men received curative treatment (152 vs 73 [95% CI: 66-85] per 100 000 men per year). There were up to 15% fewer prostate cancer deaths in the scenario with high-diagnostic activity (incidence rate ratio, 0.85; 95% CI, 0.82-0.88).

    CONCLUSIONS AND RELEVANCE: This studys results suggest that increased prostate-specific antigen testing and diagnostic activity are associated with a larger number of men being diagnosed with prostate cancer, predominately with low- and intermediate-risk disease. The increased diagnostic activity was associated with a 2-fold increase in curative treatment and a modest decrease in mortality.

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  • 48.
    Berglund, Gunilla
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Petersson, Lena-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Eriksson, Karin C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Wallenius, Imke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Roshanai, Afsaneh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Nordin, Karin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Sjödén, Per-Olow
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    "Between Men": A psychosocial rehabilitation programme for men with prostate cancer2007In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 46, no 1, p. 83-89Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate the effect of psychosocial rehabilitation on newly diagnosed prostate cancer patients. The “Between Men” programme consisted of seven weekly sessions of physical training (Phys) alone, information (Info) alone or physical training plus information (PhysInfo). After diagnoses, patients (n =211) were consecutively included, stratified and randomised to one of four groups: Phys, Info, PhysInfo or standard care control (C). A nurse specialised in urology, an urologist and a physiotherapist performed the interventions. Patients were followed up during one year with mailed standardised questionnaires. It could not be assumed that the “Between Men” programme had any effect on patients’ anxiety and depression (HADS). Health-related quality of life (HRQOL) was associated with stage of disease but not with psychosocial intervention. Thus, Physical Function (PF), Role Function (RF) and Fatigue (FA) were inferior among patients with, than without, metastases of prostate cancer both at baseline and at the 12-month follow-up. This randomized study did not demonstrate any significant effect of psychosocial rehabilitation among prostate cancer patients. Considering the low rate (1/2), of included/eligible patients a less complicated design (intervention versus control) would have been preferred in order to increase power.

  • 49.
    Bergman, Emma Ahlen
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden..
    Hartana, Ciputra Adijaya
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden..
    Johansson, Markus
    Sundsvall Hosp, Dept Urol, Sundsvall, Sweden.;Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Linton, Ludvig B.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden..
    Berglund, Sofia
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden..
    Hyllienmark, Martin
    TLA Targeted Immunotherapies AB, Stockholm, Sweden..
    Lundgren, Christian
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden..
    Holmström, Benny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Palmqvist, Karin
    Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.;Ostersund Cty Hosp, Urol Sect, Dept Surg, Ostersund, Sweden..
    Hansson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Alamdari, Farhood
    Vastmanland Hosp, Dept Urol, Vasteras, Sweden..
    Huge, Ylva
    Linkoping Univ, Div Urol, Dept Clin & Expt Med, Linkoping, Sweden..
    Aljabery, Firas
    Linkoping Univ, Div Urol, Dept Clin & Expt Med, Linkoping, Sweden..
    Riklund, Katrine
    Umea Univ, Dept Radiat Sci, Diagnost Radiol, Umea, Sweden..
    Winerdal, Malin E.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden..
    Krantz, David
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden..
    Zirakzadeh, A. Ali
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.;Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Marits, Per
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden..
    Sjöholm, Louise K.
    Karolinska Inst, Dept Clin Neurosci, Ctr Mol Med, Stockholm, Sweden..
    Sherif, Amir
    Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.;Umea Univ, Dept Radiat Sci, Diagnost Radiol, Umea, Sweden..
    Winqvist, Ola
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden..
    Increased CD4(+) T cell lineage commitment determined by CpG methylation correlates with better prognosis in urinary bladder cancer patients2018In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 10, article id 102Article in journal (Refereed)
    Abstract [en]

    Background: Urinary bladder cancer is a common malignancy worldwide. Environmental factors and chronic inflammation are correlated with the disease risk. Diagnosis is performed by transurethral resection of the bladder, and patients with muscle invasive disease preferably proceed to radical cystectomy, with or without neoadjuvant chemotherapy. The anti-tumour immune responses, known to be initiated in the tumour and draining lymph nodes, may play a major role in future treatment strategies. Thus, increasing the knowledge of tumour-associated immunological processes is important. Activated CD4(+) T cells differentiate into four main separate lineages: Th1, Th2, Th17 and Treg, and they are recognized by their effector molecules IFN-gamma, IL-13, IL-17A, and the transcription factor Foxp3, respectively. We have previously demonstrated signature CpG sites predictive for lineage commitment of these four major CD4(+ )T cell lineages. Here, we investigate the lineage commitment specifically in tumour, lymph nodes and blood and relate them to the disease stage and response to neoadjuvant chemotherapy.

    Results: Blood, tumour and regional lymph nodes were obtained from patients at time of transurethral resection of the bladder and at radical cystectomy. Tumour-infiltrating CD4(+ )lymphocytes were significantly hypomethylated in all four investigated lineage loci compared to CD4(+) lymphocytes in lymph nodes and blood (lymph nodes vs rumour-infiltrating lymphocytes: IFNG -4229 bp p < 0.0001, IL13 -11 bp p < 0.05, IL17A -122 bp p < 0.01 and FOXP3 -77 bp p> 0.05). Examination of individual lymph nodes displayed different methylation signatures, suggesting possible correlation with future survival. More advanced post-cystectomy tumour stages correlated significantly with increased methylation at the IFNG -4229 bp locus. Patients with complete response to neoadjuvant chemotherapy displayed significant hypomethylation in CD4(+ )T cells for all four investigated loci, most prominently in IFNG p < 0.0001. Neoadjuvant chemotherapy seemed to result in a relocation of Th1-committed CD4(+) T cells from blood, presumably to the tumour, indicated by shifts in the methylation patterns, whereas no such shifts were seen for lineages corresponding to IL13, IL17A and FOXP3.

    Conclusion: Increased lineage commitment in CD4(+) T cells, as determined by demethylation in predictive CpG sites, is associated with lower post-cystectomy tumour stage, complete response to neoadjuvant chemotherapy and overall better outcome, suggesting epigenetic profiling of CD4(+) T cell lineages as a useful readout for clinical staging.

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  • 50.
    Beukers, Willemien
    et al.
    Erasmus MC, Dept Pathol, POB 2040, NL-3000 CA Rotterdam, Netherlands..
    van der Keur, Kirstin A.
    Erasmus MC, Dept Pathol, POB 2040, NL-3000 CA Rotterdam, Netherlands..
    Kandimalla, Raju
    Erasmus MC, Dept Pathol, POB 2040, NL-3000 CA Rotterdam, Netherlands..
    Vergouwe, Yvonne
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands..
    Steyerberg, Ewout W.
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands..
    Boormans, Joost L.
    Erasmus MC, Dept Urol, Rotterdam, Netherlands..
    Jensen, Jorgen B.
    Aarhus Univ Hosp, Dept Urol, Aarhus, Denmark..
    Lorente, Jose A.
    Hosp del Mar, Serv Urol, Barcelona, Spain..
    Real, Francisco X.
    Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.;Spanish Natl Canc Res Centre CNIO, Canc Cell Biol Programme, Epithelial Carcinogenesis Grp, Madrid, Spain..
    Segersten, Ulrike
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Orntoft, Torben F.
    Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark..
    Malats, Nuria
    Spanish Natl Canc Res Centre CNIO, Canc Cell Biol Programme, Epithelial Carcinogenesis Grp, Madrid, Spain..
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Dyrskjot, Lars
    Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark..
    Zwarthoff, Ellen C.
    Erasmus MC, Dept Pathol, POB 2040, NL-3000 CA Rotterdam, Netherlands..
    FGFR3, TERT and OTX1 as a Urinary Biomarker Combination for Surveillance of Patients with Bladder Cancer in a Large Prospective Multicenter Study2017In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 197, no 6, p. 1410-1418Article in journal (Refereed)
    Abstract [en]

    Purpose: Patients with nonmuscle invasive bladder cancer are followed with frequent cystoscopies. In this study FGFR3, TERT and OTX1 were investigated as a diagnostic urinary marker combination during followup of patients with primary nonmuscle invasive bladder cancer.

    Materials and Methods: In this international, multicenter, prospective study 977 patients with nonmuscle invasive bladder cancer were included. A total of 2,496 urine samples were collected prior to cystoscopy during regular visits. Sensitivity was estimated to detect concomitant recurrences. Kaplan-Meier curves were used to estimate the development of future recurrences after urinalysis and a negative cystoscopy.

    Results: Sensitivity of the assay combination for recurrence detection was 57% in patients with primary low grade, nonmuscle invasive bladder cancer. However, sensitivity was 83% for recurrences that were pT1 or muscle invasive bladder cancer. Of the cases 2% progressed to muscle invasive bladder cancer. Sensitivity for recurrence detection in patients with primary high grade disease was 72% and 7% of them had progression to muscle invasive bladder cancer. When no concomitant tumor was found by cystoscopy, positive urine samples were more frequently followed by a recurrence over time compared to a negative urine sample (58% vs 36%, p < 0.001). High stage recurrences were identified within 1 year after a positive urine test and a negative cystoscopy.

    Conclusions: Recurrences in patients with primary nonmuscle invasive bladder cancer can be detected by a combination of urine assays. This study supports the value of urinalysis as an alternative diagnostic tool in patients presenting with low grade tumors and as a means to identify high stage tumors earlier.

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