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  • 1.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. 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 Therapy2017Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, nr 3, s. 330-336Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 2.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    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 outcome2019Inngår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, nr 5, s. 435-445Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 3. Arnsrud Godtman, Rebecka
    et al.
    Månsson, Marianne
    Bratt, Ola
    Robinsson, David
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    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 study2019Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, nr 6, s. 378-384Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 4.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Fac Life Sci & Med, Div Canc Studies, TOUR, London, England.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. 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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. 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 study2018Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, nr 11, s. 2254-2262Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 5.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Kings Coll London, Canc Epidemiol Grp, Div Canc Studies, London, England.;Reg Canc Ctr, Uppsala, Sweden..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. 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 categories2016Inngår i: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 5, nr 6, s. 1307-1318Artikkel i tidsskrift (Fagfellevurdert)
    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.

    Fulltekst (pdf)
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  • 6.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Biobank Res, Umea, Sweden.
    Holmberg, Lars
    Kings Coll London, Translat Oncol & Urol Res, London, England.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    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 study2019Inngår i: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 30, nr 2, s. 195-206Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 7.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. 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 Screening2018Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, nr 6, s. 961-967Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 8.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Holmberg, Lars
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    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 Cancer2019Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, nr 4, s. 676-683Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 9.
    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 universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Biobank Res, Umea, Sweden.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Sch Canc & Pharmaceut Studies Translat Oncol, Sch Canc & Pharmaceut Studies, TOUR, London, England.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    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 study2019Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, artikkel-id 612Artikkel i tidsskrift (Fagfellevurdert)
    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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  • 10.
    Bjartell, Anders
    et al.
    Skane Univ Hosp, Dept Urol, SE-20502 Malmo, Sweden.;Lund Univ, Div Urol Canc, Dept Translat Med, S-22100 Lund, Sweden..
    Bottai, Matteo
    Karolinska Inst, Inst Environm Med, Unit Biostat, Stockholm, Sweden..
    Persson, Josefin
    Sahlgrens Univ Hosp, Dept Cardiothorac Surg, Gothenburg, Sweden..
    Bratt, Ola
    Lund Univ, Div Urol Canc, Dept Translat Med, S-22100 Lund, Sweden.;Cambridge Univ Hosp, Dept Urol, Cambridge, England..
    Damber, Jan-Erik
    Univ Gothenburg, Inst Clin Sci Sahlgrenska Acad, Dept Urol, Gothenburg, Sweden..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Akre, Olof
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Urol, Stockholm, Sweden..
    Prediction of clinical progression after radical prostatectomy in a nationwide population-based cohort2016Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, nr 4, s. 255-259Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The aim of this study was to create a model for predicting progression-free survival after radical prostatectomy for localized prostate cancer. Material and methods: The risk of biochemical recurrence (BCR) was modelled in a cohort of 3452 men aged 70 years or younger who were primarily treated with radical prostatectomy after being diagnosed between 2003 and 2006 with localized prostate cancer [clinical stage T1c-T2, Gleason score 5-10, N0/NX, M0/MX, prostate-specific antigen (PSA)<20 ng/ml]. The cohort was split into two: one cohort for model development (n = 3452) and one for validation (n = 1762). BCR was defined as two increasing PSA values of at least 0.2 ng/ml, initiation of secondary therapy, distant metastases or death from prostate cancer. Multivariable Cox proportional hazard regression was applied, predictive performance was assessed using the bootstrap resampling technique to calculate the c index, and calibration of the model was evaluated by comparing predicted and observed Kaplan-Meier 1 year BCR. Results: The overall 5 year progression-free survival was 83% after a median follow-up time of 6.8 years in the development cohort and 7.3 years in the validation cohort. The final model included T stage, PSA level, primary and secondary Gleason grade, and number of positive and negative biopsies. The c index for discrimination between high and low risk of recurrence was 0.68. The probability of progression-free survival ranged from 22% to 97% over the range of risk scores in the study population. Conclusions: This model is based on nationwide population-based data and can be used with a fair predictive accuracy to guide decisions on clinical follow-up after prostatectomy. An online calculator for convenient clinical use of the model is available at www.npcr.se/nomogram

  • 11.
    Björklund, Johan
    et al.
    Karolinska Univ Hosp, Dept Urol, Solna, Sweden..
    Folkvaljon, Yasin
    Uppsala Univ Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Cole, Alexander
    Harvard Med Sch, Brigham & Womens Hosp, Div Urol Surg, Boston, MA USA..
    Carlsson, Stefan
    Karolinska Inst, Urol Sect, Dept Mol Med & Surg, Stockholm, Sweden..
    Robinson, David
    Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden.;Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Loeb, Stacy
    NYU, Dept Urol Populat Hlth, Laura & Isaac Perlmutter Canc Ctr, New York, NY USA..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Akre, Olof
    Karolinska Univ Hosp, Dept Urol, Solna, Sweden.;Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Postoperative mortality 90 days after robot-assisted laparoscopic prostatectomy and retropubic radical prostatectomy: a nationwide population-based study2016Inngår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, nr 2, s. 302-306Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To assess 90-day postoperative mortality after robot-assisted laparoscopic radical prostatectomy (RARP) and retropubic radical prostatectomy (RRP) using nationwide population-based registry data. Patients and Methods We conducted a cohort study using the National Prostate Cancer Register of Sweden, including 22 344 men with localized prostate cancer of clinical stage T1-T3, whose prostate-specific antigen levels were <50 mu g/mL and who had undergone primary radical prostatectomy in the period 1998-2012. Vital status was ascertained through the Total Population Register. The rates for 90-day postoperative mortality were analysed using logistic regression analysis, and comparisons of 90-day mortality with the background population were made using standardized mortality ratios (SMRs). Results Of the 14 820 men who underwent RRP, 29 (0.20%) died, and of the 7 524 men who underwent RARP, 10 (0.13%) died. Mortality in the cohort during the 90-day postoperative period was lower than in an age-matched background population: SMR 0.57 (95% confidence interval [CI] 0.39-0.75). There was no statistically significant difference in 90-day mortality according to surgical method: RARP vs RRP odds ratio (OR) 1.14; 95% CI 0.46-2.81. Postoperative 90-day mortality decreased over time: 2008-2012 vs 1998-2007 OR 0.44; 95% CI 0.21-0.95, mainly because of lower mortality after RARP. Conclusion The 90-day postoperative mortality rates were low after RARP and RRP and there was no statistically significant difference between the methods. Given the long life expectancy among men with low-and intermediate-risk prostate cancer, very low postoperative mortality is a prerequisite for RP, which was fulfilled by both RRP and RARP. The selection of healthy men for RP is highlighted by the lower 90-day mortality after RP compared with the background population.

  • 12. Bjørge, Tone
    et al.
    Häggström, Christel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Ghaderi, Sara
    Nagel, Gabriele
    Manjer, Jonas
    Tretli, Steinar
    Ulmer, Hanno
    Harlid, Sophia
    Rosendahl, Ann H
    Lang, Alois
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stocks, Tanja
    Engeland, Anders
    BMI and weight changes and risk of obesity-related cancers: a pooled European cohort study2019Inngår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 48, nr 6, s. 1872-1885Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Obesity is an established risk factor for several cancers. Adult weight gain has been associated with increased cancer risk, but studies on timing and duration of adult weight gain are relatively scarce. We examined the impact of BMI (body mass index) and weight changes over time, as well as the timing and duration of excess weight, on obesity- and non-obesity-related cancers.

    METHODS: We pooled health data from six European cohorts and included 221 274 individuals with two or more height and weight measurements during 1972-2014. Several BMI and weight measures were constructed. Cancer cases were identified through linkage with national cancer registries. Hazard ratios (HRs) of cancer with 95% confidence intervals (CIs) were derived from time-dependent Cox-regression models.

    RESULTS: During follow-up, 27 881 cancer cases were diagnosed; 9761 were obesity-related. The HR of all obesity-related cancers increased with increasing BMI at first and last measurement, maximum BMI and longer duration of overweight (men only) and obesity. Participants who were overweight before age 40 years had an HR of obesity-related cancers of 1.16 (95% CI 1.02, 1.32) and 1.15 (95% CI 1.04, 1.27) in men and women, respectively, compared with those who were not overweight. The risk increase was particularly high for endometrial (70%), male renal-cell (58%) and male colon cancer (29%). No positive associations were seen for cancers not regarded as obesity-related.

    CONCLUSIONS: Adult weight gain was associated with increased risk of several major cancers. The degree, timing and duration of overweight and obesity also seemed to be important. Preventing weight gain may reduce the cancer risk.

  • 13. Bonn, Stephanie E
    et al.
    Wiklund, Fredrik
    Sjölander, Arvid
    Szulkin, Robert
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Holmberg, Erik
    Grönberg, Henrik
    Bälter, Katarina
    Body mass index and weight change in men with prostate cancer: progression and mortality.2014Inngår i: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 25, nr 8, s. 933-943Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Body mass index (BMI) is a modifiable lifestyle factor that has been associated with an increased risk of fatal prostate cancer and biochemical recurrence. The main purpose of the present study was to investigate the association between the exposure BMI at the time of a prostate cancer diagnosis and weight change after diagnosis, and the outcomes of prostate cancer progression and mortality in a large cohort study.

    METHODS: Data from 4,376 men diagnosed with clinically localized prostate cancer between 1997 and 2002 were analyzed. BMI and weight change were self-reported in 2007. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were estimated in complete-case analysis (n = 3,214) using Cox proportional hazards models.

    RESULTS: Progression was experienced among 639 (14.6 %) of the study participants, and in total, 450 (10.3 %) deaths of any cause and 134 (3.1 %) prostate cancer-specific deaths were recorded during follow-up. Obese men had a 47 % increased rate of overall mortality compared to normal weight men (HR 1.47, 95 % CI 1.03-2.10). No statistically significant associations were found for BMI and prostate cancer progression or prostate cancer-specific mortality. A weight loss >5 % after diagnosis almost doubled the rate of overall mortality compared to maintaining a stable weight (HR 1.94, 95 % CI 1.41-2.66), while a weight gain >5 % was associated with an almost doubled increased rate of prostate cancer-specific mortality (HR 1.93, 95 % CI 1.18-3.16).

    CONCLUSIONS: Being obese was associated with an increased rate of overall mortality, and gaining weight after a prostate cancer diagnosis was associated with an increased rate of prostate cancer-specific mortality.

  • 14.
    Bosco, Cecilia
    et al.
    Kings Coll London, Div Canc Studies, TOUR, London, England..
    Garmo, Hans
    Kings Coll London, Div Canc Studies, TOUR, London, England.;Akad Sjukhuset, Reg Canc Ctr, Uppsala, Sweden..
    Adolfsson, Jan
    Karolinska Inst, CLINTEC Dept, Stockholm, Sweden..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Div Canc Studies, TOUR, London, England.;Akad Sjukhuset, Reg Canc Ctr, Uppsala, Sweden..
    Nilsson, Per
    Lund Univ, Skane Univ Hosp, Dept Hematol Oncol & Radiat Phys, Lund, Sweden..
    Gunnlaugsson, Adalsteinn
    Lund Univ, Skane Univ Hosp, Dept Hematol Oncol & Radiat Phys, Lund, Sweden..
    Widmark, Anders
    Umea Univ, Dept Radiat Sci, Oncol, Umea, Sweden..
    Van Hemelrijck, Mieke
    Kings Coll London, Div Canc Studies, TOUR, London, England.;Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Prostate Cancer Radiation Therapy and Risk of Thromboembolic Events2017Inngår i: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 97, nr 5, s. 1026-1031Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To investigate the risk of thromboembolic disease (TED) after radiation therapy (RT) with curative intent for prostate cancer (PCa).

    Patients and Methods: We identified all men who received RT as curative treatment (n=9410) and grouped according to external beam RT (EBRT) or brachytherapy (BT). By comparing with an age-and county-matched comparison cohort of PCa-free men (n = 46,826), we investigated risk of TED after RT using Cox proportional hazard regression models. The model was adjusted for tumor characteristics, demographics, comorbidities, PCa treatments, and known risk factors of TED, such as recent surgery and disease progression.

    Results: Between 2006 and 2013, 6232 men with PCa received EBRT, and 3178 underwent BT. A statistically significant association was found between EBRT and BT and risk of pulmonary embolism in the crude analysis. However, upon adjusting for known TED risk factors these associations disappeared. No significant associations were found between BT or EBRT and deep venous thrombosis.

    Conclusion: Curative RT for prostate cancer using contemporary methodologies was not associated with an increased risk of TED.

    Fulltekst (pdf)
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  • 15.
    Bosco, Cecilia
    et al.
    Kings Coll London, Sch Canc & Pharmaceut Sci Translat Oncol & Urol R, London, England.
    Wong, Chloe
    Kings Coll London, Sch Canc & Pharmaceut Sci Translat Oncol & Urol R, London, England.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci Translat Oncol & Urol R, London, England.; Uppsala Univ, Reg Canc Ctr, Uppsala, Sweden..
    Crawley, Danielle
    Kings Coll London, Sch Canc & Pharmaceut Sci Translat Oncol & Urol R, London, England.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Sch Canc & Pharmaceut Sci Translat Oncol & Urol R, London, England.
    Hammar, Niklas
    Inst Environm Med, Epidemiol Unit, Stockholm, Sweden.; Global Med Affairs AstraZeneca, Med Evidence & Observat Res, Molndal, Sweden..
    Adolfsson, Jan
    Karolinska Inst, CLINTEC Dept, Stockholm, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci Translat Oncol & Urol R, London, England.
    Drugs for metabolic conditions and prostate cancer death in men on GnRH agonists.2018Inngår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 121, nr 2, s. 260-267Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To evaluate whether drugs for metabolic conditions influence prostate cancer-specific mortality in men starting gonadotrophin-releasing hormone (GnRH) agonists, as it is unclear whether metabolic syndrome and its related drugs is affecting treatment response in men with prostate cancer on GnRH agonists.

    PATIENTS AND METHODS: We selected all men receiving GnRH agonists as primary treatment in the Prostate Cancer data Base Sweden (PCBaSe) (n = 9267). Use of drugs for metabolic conditions (i.e. anti-diabetes, anti-dyslipidaemia, and antihypertension) in relation to all-cause, cardiovascular disease (CVD), and prostate cancer-specific death were studied using multivariate Cox proportional hazard and Fine and Gray competing regression models.

    RESULTS: In all, 6322 (68%) men used at least one drug for a metabolic condition at GnRH agonist initiation: 46% on antihypertensive drugs only, 32% on drugs for dyslipidaemia and hypertension, and ~10% on drugs for more than two metabolic conditions. Cox models indicated a weak increased risk of prostate cancer death in men who were on drugs for hypertension only (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.03-1.23) or drugs for hyperglycaemia (HR 1.19, 95% CI 1.06-1.35) at GnRH agonist initiation. However, upon taking into account competing risk from CVD death, none of the drugs for metabolic conditions were associated with an increased risk of prostate cancer death.

    CONCLUSION: We did not find evidence for a better or worse response to GnRH agonists in men with prostate cancer who were also on drugs for hypertension, dyslipidaemia, or hyperglycaemia.

  • 16.
    Bratt, Ola
    et al.
    Lund Univ, Div Urol Canc, Dept Translat Med Urol, Lund, Sweden.;Cambridge Univ Hosp, CamPARI Clin, Dept Urol, Cambridge, England..
    Drevin, Linda
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Akre, Olof
    Karolinska Inst, Dept Urol, Stockholm, Sweden..
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Family History and Probability of Prostate Cancer, Differentiated by Risk Category: A Nationwide Population-Based Study2016Inngår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 108, nr 10, artikkel-id djw110Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Familial prostate cancer risk estimates are inflated by clinically insignificant low-risk cancer, diagnosed after prostate-specific antigen testing. We provide age-specific probabilities of non-low-and high-risk prostate cancer. Methods: Fifty-one thousand, eight hundred ninety-seven brothers of 32 807 men with prostate cancer were identified in Prostate Cancer data Base Sweden (PCBaSe). Nelson-Aalen estimates with 95% confidence intervals (CIs) were calculated for cumulative, family history-stratified probabilities of any, non-low-(any of Gleason score >= 7, prostate-specific antigen [PSA] >= 10 ng/mL, T3-4, N1, and/or M1) and high-risk prostate cancer (Gleason score >= 8 and/or T3-4 and/or PSA >= 20 ng/mL and/or N1 and/or M1). Results: The population probability of any prostate cancer was 4.8% (95% CI = 4.8% to 4.9%) at age 65 years and 12.9% (95% CI = 12.8% to 12.9%) at age 75 years, of non-low-risk prostate cancer 2.8% (95% CI = 2.7% to 2.8%) at age 65 years and 8.9% (95% CI = 8.8% to 8.9%) at age 75 years, and of high-risk prostate cancer 1.4% (95% CI = 1.3% to 1.4%) at age 65 years and 5.2% (95% CI = 5.1% to 5.2%) at age 75 years. For men with one affected brother, probabilities of any prostate cancer were 14.9% (95% CI = 14.1% to 15.8%) at age 65 years and 30.3% (95% CI = 29.3% to 31.3%) at age 75 years, of non-low-risk prostate cancer 7.3% (95% CI = 6.7% to 7.9%) at age 65 years and 18.8% (95% CI = 17.9% to 19.6%) at age 75 years, and of high-risk prostate cancer 3.0% (95% CI = 2.6% to 3.4%) at age 65 years and 8.9% (95% CI = 8.2% to 9.5%) at age 75 years. Probabilities were higher for men with a stronger family history. For example, men with two affected brothers had a 13.6% (95% CI = 9.9% to 17.6 %) probability of high-risk cancer at age 75 years. Conclusions: The age-specific probabilities of non-low-and high-risk cancer presented here are more informative than relative risks of any prostate cancer and more suitable to use for counseling men with a family history of prostate cancer.

    Fulltekst (pdf)
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  • 17.
    Bratt, Ola
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Urol, SE-41345 Gothenburg, Sweden.
    Holmberg, Erik
    Sahlgrens Univ Hosp, Reg Canc Ctr, Vastra Gotaland, Gothenburg, Sweden.
    Andren, Ove
    Orebro Univ Hosp, Dept Urol, Orebro, Sweden.
    Carlsson, Stefan
    Karolinska Inst, Dept Mol Med & Surg, Sect Urol, Stockholm, Sweden.
    Drevin, Linda
    Reg Canc Ctr, Uppsala, Sweden.
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Josefsson, Andreas
    Univ Gothenburg, Sahlgrenska Acad, Dept Urol, SE-41345 Gothenburg, Sweden.
    Nyberg, Maria
    Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden.
    Sandberg, Jonas
    Norrland Univ Hosp, Dept Urol, Umea, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Robinsson, David
    Dept Urol, Jönköping, Jönköping Count, Sweden.
    The Value of an Extensive Transrectal Repeat Biopsy with Anterior Sampling in Men on Active Surveillance for Low-risk Prostate Cancer: A Comparison from the Randomised Study of Active Monitoring in Sweden (SAMS)2019Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, nr 4, s. 461-466Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: A systematic repeat biopsy is recommended for men starting on active surveillance for prostate cancer, but the optimal number and distribution of cores are unknown. Objective: To evaluate an extensive repeat transrectal biopsy with anterior sampling in men starting on active surveillance. Design, setting, and participants: Randomised multicentre trial. From 2012 to 2016, 340 Swedish men, aged 40-75 yr, with recently diagnosed low-volume Gleason grade group 1 prostate cancer were included. Intervention: Either an extensive transrectal biopsy with anterior sampling (median 19 cores) or a standard transrectal biopsy (median 12 cores). Outcome measurements and statistical analysis: Primary outcome measure: Gleason grade group >= 2 cancer. Secondary outcomes: Cancer in anteriorly directed biopsy cores and postbiopsy infection. Nonparametric statistical tests were applied. Results and limitations: Gleason grade group >= 2 cancer was detected in 16% of 156 men who had an extensive biopsy and in 10% of 164 men who had a standard biopsy, a 5.7% difference (95% confidence interval [CI]-0.2% to 13%, p = 0.09). There was a strong linear association between prostate-specific antigen (PSA) density and cancer in the anteriorly directed biopsy cores. The odds ratios for cancer in the anteriorly directed cores were for any cancer 2.2 (95% CI 1.3-3.9, p = 0.004) and for Gleason grade group >= 2 cancer 2.3 (95% CI 1.2-4.4, p = 0.015) per 0.1-ng/ml/cm(3) increments. Postbiopsy infections were equally common in the two groups. A limitation is that magnetic resonance imaging was not used. Conclusions: The trial did not support general use of the extensive transrectal repeat biopsy template, but cancer in the anteriorly directed cores was common, particularly in men with high PSA density. The higher the PSA density, the stronger the reason to include anterior sampling at a systematic repeat biopsy. Patient summary: This trial compared two different templates for transrectal prostate biopsy in men starting on active surveillance for low-risk prostate cancer. Cancer was often found in the front part of the prostate, which is not sampled on a standard prostate biopsy. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 18.
    Cazzaniga, Walter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. IRCCS Osped San Raffaele, Unit Urol URI, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Garmo, Hans
    Uppsala Univ Hosp, Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden;Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG-4) study2019Inngår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 123, nr 3, s. 421-428Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To investigate if results in terms of absolute risk in mature randomised trials are relevant for contemporary decision-making. To do so, we compared the outcome for men in the radical prostatectomy (RP) arm of the Scandinavian Prostate Cancer Group Study number 4 (SPCG-4) randomised trial with matched men treated in a contemporary era before and after compensation for the grade migration and grade inflation that have occurred since the 1980s.

    PATIENTS AND METHODS: A propensity score-matched analysis of prostate cancer mortality and all-cause mortality in the SPCG-4 and matched men in the National Prostate Cancer Register (NPCR) of Sweden treated in 1998-2006 was conducted. Cumulative incidence of prostate cancer mortality and all-cause mortality was calculated. Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for a matching on original Gleason Grade Groups (GGG) and second, matching with GGG increased one unit for men in the NPCR.

    RESULTS: Matched men in the NPCR treated in 2005-2006 had half the risk of prostate cancer mortality compared to men in the SPCG-4 (HR 0.46, 95% CI 0.19-1.14). In analysis of men matched on an upgraded GGG in the NPCR, this difference was mitigated (HR 0.73, 95% CI 0.36-1.47).

    CONCLUSIONS: Outcomes after RP for men in the SPCG-4 cannot be directly applied to men in the current era, mainly due to grade inflation and grade migration. However, by compensating for changes in grading, similar outcomes after RP were seen in the SPCG-4 and NPCR. In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for.

  • 19.
    Cazzaniga, Walter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Univ Vita Salute San Raffaele, Osped San Raffaele, Unit Urol URI, IRCCS,Div Expt Oncol, Milan, Italy.
    Godtman, Rebecka Arnsrud
    Univ Goteborg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol,Sahlgrenska Univ Hosp, Gothenburg, Sweden.
    Carlsson, Stefan
    Karolinska Univ Hosp, Div Urol, Stockholm, Sweden;Karolinska Inst, Dept Mol Med & Surg MMK, Stockholm, Sweden.
    Ahlgren, Göran
    Lund Univ, Dept Urol, Skane Univ Hosp, Skane, Sweden.
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Hugosson, Jonas
    Univ Goteborg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol,Sahlgrenska Univ Hosp, Gothenburg, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Population-based, nationwide registration of prostatectomies in Sweden2019Inngår i: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 120, nr 4, s. 803-812Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction Radical prostatectomy (RP) is a common surgical procedure with a risk of postoperative erectile dysfunction and urinary incontinence. There is a need for data on RP as a basis for quality assurance and benchmarking. Methods In 2015, prostatectomies in Sweden (PiS) form was implemented in the National Prostate Cancer Register (NPCR) of Sweden with data on pre-, peri- and post-operative variables. Results Out of all radical prostatectomies performed in 2016 in Sweden, 3096/3881 (80%) were registered in PiS. A total of 2605 (84%) were robot-assisted radical prostatectomy (RARP) and 491 (16%) were RRP (retropubic radical prostatectomy). RARP was performed by 91 surgeons of whom 47% operated more than 25 RP/year; and RRP was performed by 69 surgeons of whom 10% performed more than 25 RP/year. RARP had a longer operative time (median operating time: RARP 155 minutes [IQR 124-190]; RRP 129 minutes [IQR 105-171]; P < .001) but was associated with smaller bleeding (median intraoperative blood loss: RARP 100 mL [IQR 50-200], RRP 700 mL [IQR 500-1100]; P < .001). Conclusions We report on a nationwide, population-based register with transparent reporting of data on the performance of radical prostatectomy. These data are needed as a basis for quality assurance with comparisons of results from individual surgeons and hospitals.

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  • 20.
    Cazzaniga, Walter
    et al.
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Ventimiglia, Eugenio
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Alfano, Massimo
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Lissbrant, Ingela Franck
    Univ Goteborg, Sahlgrenska Acad, Dept Oncol, Inst Clin Sci, Gothenburg, Sweden.
    Carlsson, Stefan
    Karolinska Univ Hosp, Div Urol, Stockholm, Sweden;Karolinska Inst, Dept Mol Med & Surg MMK, Stockholm, Sweden.
    Styrke, Johan
    Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Salonia, Andrea
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Mini Review on the Use of Clinical Cancer Registers for Prostate Cancer: The National Prostate Cancer Register (NPCR) of Sweden2019Inngår i: FRONTIERS IN MEDICINE, ISSN 2296-858X, Vol. 6, artikkel-id 51Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Given the increasing prevalence of cancer, it is vital to systematically collect data in order to monitor disease trends and quality of cancer care. For this purpose, clinical cancer registries have been developed in some countries. These registers are intended to be used as a basis for quality assurance and quality improvement, but they also constitute a rich resource of real world data for research. The aim of thismini-review was to describe the structure and the organization of the National Prostate Cancer Register (NPCR) with some examples on how data in NPCR have affected prostate cancer care in Sweden.

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  • 21.
    Crawley, Danielle
    et al.
    Kings Coll London, Translat Oncol & Urol Res Grp, London, England.
    Chamberlain, Florence
    Guys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England.
    Garmo, Hans
    Kings Coll London, Translat Oncol & Urol Res Grp, London, England.
    Rudman, Sarah
    Guys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Med Prod Agcy, Uppsala, Sweden.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Translat Oncol & Urol Res Grp, London, England.
    Adolfsson, Jan
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Carroll, Paul
    Guys & St Thomas NHS Fdn Trust, Dept Diabet & Endocrinol, London, England.
    Van Hemelrijck, Mieke
    Kings Coll London, Translat Oncol & Urol Res Grp, London, England.
    A systematic review of the literature exploring the interplay between prostate cancer and type two diabetes mellitus2018Inngår i: ecancermedicalscience, ISSN 1754-6605, E-ISSN 1754-6605, Vol. 12, artikkel-id 802Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Prostate cancer (PCa) and type two diabetes mellitus (T2DM) are both increasing prevalent conditions and often occur concurrently. However, the relationship between the two is more complex than just two prevalent conditions co-existing. This review systematically explores the literature around the interplay between the two conditions. It covers the impact of pre-existing T2DM on PCa incidence, grade and stage, as well as exploring the impact of T2DM on PCa outcomes and mortality and the interaction between T2DM and PCa treatments.

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  • 22.
    Crawley, Danielle
    et al.
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England..
    Garmo, Hans
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England..
    Rudman, Sarah
    Guys & St Thomas NHS Fdn Trust, London, England.;Kings Coll Londons Comprehens, Biomed Res Ctr, London, England..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Häggström, Christel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.;Umea Univ, Dept Biobank Res, Umea, Sweden..
    Zethelius, Björn
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Holmberg, Lars
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England..
    Adolfsson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Van Hemelrijck, Mieke
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England..
    Association between duration and type of androgen deprivation therapy and risk of diabetes in men with prostate cancer2016Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 139, nr 12, s. 2698-2704Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Androgen deprivation therapy (ADT) for prostate cancer (PCa) increases risk of type 2 diabetes (T2DM); however the association between types and duration of ADT has not been fully elucidated. We examined how type and duration of ADT affects risk of T2DM. Using data from Prostate Cancer database Sweden (PCBaSe) we investigated risk of T2DM in a cohort of 34,031 men with PCa on ADT; i.e., anti-androgens (AA), orchiectomy, or gonadotropin-releasing hormone (GnRH) agonists compared to an age-matched, PCa-free comparison cohort (n=167,205) using multivariate Cox proportional hazard regression. T2DM was defined as a newly filled prescription for metformin, sulphonylurea, or insulin in the Prescribed Drug Register. A total of 21,874 men with PCa received GnRH agonists, 9,143 AA and 3,014 underwent orchiectomy. Risk of T2DM was increased in men in the GnRH agonists/orchiectomy group during the first 3 years of ADT [i.e., 121.5 years HR: 1.61 (95% CI: 1.36-1.91)], compared to PCa-free men. The risk decreased thereafter (e.g., 324 years HR: 1.17 (95% CI: 0.98-1.40)). Conversely, no increased risk was seen in men on AA (HR: 0.74 (95% CI: 0.65-0.84). The incidence of T2DM per 1,000 person-years was 10 for PCa-free men, 8 for men on AA, and 13 for men on GnRH agonists/orchiectomy. Duration of ADT has a significant impact on risk of T2DM. With the peak after three years of treatment, our data indicates that men on ADT, even for a limited period of time, such as adjuvant to radiotherapy, are at increased risk of T2DM.

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  • 23.
    Crawley, Danielle
    et al.
    Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res TOUR, London, England.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res TOUR, London, England.
    Rudman, Sarah
    Guys & St Thomas NHS Fdn Trust & Kings Coll Londo, Comprehens Biomed Res Ctr, London, England.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Med Prod Agcy, Uppsala, Sweden.
    Armes, Jo
    Kings Coll London, Florence Nightingale Fac Nursing & Midwifery, London, England.
    Holmberg, Lars
    Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res TOUR, London, England.
    Adolfsson, Jan
    Kings Coll London, Florence Nightingale Fac Nursing & Midwifery, London, England;Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res TOUR, London, England.
    Does a prostate cancer diagnosis affect management of pre-existing diabetes? Results from PCBaSe Sweden: a nationwide cohort study2018Inngår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 8, nr 3, artikkel-id e020787Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives Both prostate cancer (PCa) and type 2 diabetes mellitus (T2DM) are increasingly prevalent conditions, which frequently coexist in men. Here, we set out to specifically examine the impact of a PCa diagnosis and its treatment on T2DM treatment. Setting This study uses observational data from Prostate Cancer database Sweden Traject. Participants The study was undertaken in a cohort of 16778 men with T2DM, of whom 962 were diagnosed with PCa during mean follow-up of 2.5 years. Primary and secondary outcome measures We investigated the association between PCa diagnosis and escalation in T2DM treatment in this cohort. A treatment escalation was defined as a new or change in anti-T2DM prescription, as recorded in the prescribed drug register (ie, change from diet to meforrnin or sulphonylurea or insulin). We also investigated how PCa diagnosis was associated with two treatment escalations. Multivariate Cox proportional hazards regression with age as a time scale was used while adjusting for educational level and initial T2DM treatment. Results We found no association between PCa diagnosis and risk of a single treatment escalation (HR 0.99, 95% Cl 0.87 to 1.13). However, PCa diagnosis was associated with an increased risk of receiving two consecutive T2DM treatment escalations (HR 1.75, 95% CI 1.38 to 2.22). This increase was strongest for men on gonadotropin-releasing hormone (GnRH) agonists (HR 3.08, 95% Cl 2.14 to 4.40). The corresponding HR for men with PCa not on hormonal treatment was 1.40 (95% CI 1.03 to 1.92) and for men with PCa on antiandrogens 0.91 (95% Cl 0.29 to 2.82). Conclusions Men with T2DM who are diagnosed with PCa, particularly those treated with GnRH agonists, were more likely to have two consecutive escalations in T2DM treatment. This suggests a need for closer monitoring of men with both PCa and T2DM, as coexistence of PCa and its subsequent treatments could potentially worsen T2DM control.

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  • 24.
    Crawley, Danielle
    et al.
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Garmo, Hans
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Rudman, Sarah
    Guys & St Thomas NHS Fdn Trust, London, England.; Kings Coll Londons, Comprehens Biomed Res Ctr, London, England. .
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Peri Operat Sci Urol & Androl, Umea, Sweden.
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Med Prod Agcy, Uppsala, Sweden.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Adolfsson, Jan
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Van Hemelrijck, Mieke
    Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer.2018Inngår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 121, nr 2, s. 209-216Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To investigate whether curative prostate cancer (PCa) treatment was received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as little is known about the influence of T2DM diagnosis on the receipt of such treatment in men with localized PCa.

    SUBJECTS AND METHODS: The Prostate Cancer database Sweden (PCBaSe) was used to obtain data on men with T2DM and PCa (n = 2210) for comparison with data on men with PCa only (n = 23 071). All men had intermediate- (T1-2, Gleason score 7 and/or prostate-specific antigen [PSA] 10-20 ng/mL) or high-risk (T3 and/or Gleason score 8-10 and/or PSA 20-50 ng/mL) localized PCa diagnosed between 1 January 2006 and 31 December 2014. Multivariate logistic regression was used to calculate the odds ratios (ORs) for receipt of curative treatment in men with and without T2DM. Overall survival, for up to 8 years of follow-up, was calculated both for men with T2DM only and for men with T2DM and PCa.

    RESULTS: Men with T2DM were less likely to receive curative treatment for PCa than men without T2DM (OR 0.78, 95% confidence interval 0.69-0.87). The 8-year overall survival rates were 79% and 33% for men with T2DM and high-risk PCa who did and did not receive curative treatment, respectively.

    CONCLUSIONS: Men with T2DM were less likely to receive curative treatment for localized intermediate- and high-risk PCa. Men with T2DM and high-risk PCa who received curative treatment had substantially higher survival times than those who did not. Some of the survival differences represent a selection bias, whereby the healthiest patients received curative treatment. Clinicians should interpret this data carefully and ensure that individual patients with T2DM and PCa are not under- nor overtreated.

  • 25. Crowe, Francesca L
    et al.
    Appleby, Paul N
    Travis, Ruth C
    Barnett, Matt
    Brasky, Theodore M
    Bueno-de-Mesquita, H Bas
    Chajes, Veronique
    Chavarro, Jorge E
    Chirlaque, Maria-Dolores
    English, Dallas R
    Gibson, Robert A
    Giles, Graham G
    Goodman, Gary E
    Henning, Susanne M
    Kaaks, Rudolf
    King, Irena B
    Kolonel, Lawrence N
    Kristal, Alan R
    Neuhouser, Marian L
    Park, Song-Yi
    Severi, Gianluca
    Siddiq, Afshan
    Stampfer, Meir J
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Tangen, Catherine M
    Tjønneland, Anne
    Trichopoulos, Dimitrios
    Tumino, Rosario
    Wilkens, Lynne R
    Key, Timothy J
    Allen, Naomi E
    Circulating fatty acids and prostate cancer risk: individual participant meta-analysis of prospective studies.2014Inngår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 106, nr 109, artikkel-id dju240Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Individual studies have suggested that some circulating fatty acids are associated with prostate cancer risk, but have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.

    METHODS: Principal investigators of prospective studies on circulating fatty acids and prostate cancer were invited to collaborate. Investigators provided individual participant data on circulating fatty acids (weight percent) and other characteristics of prostate cancer cases and controls. Prostate cancer risk by study-specific fifths of 14 fatty acids was estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided.

    RESULTS: Five thousand and ninety-eight case patients and 6649 control patients from seven studies with an average follow-up of 5.1 (SD = 3.3) years were included. Stearic acid (18:0) was inversely associated with total prostate cancer (odds ratio [OR] Q5 vs Q1 = 0.88, 95% confidence interval [CI] = 0.78 to 1.00, P trend = .043). Prostate cancer risk was, respectively, 14% and 16% greater in the highest fifth of eicosapentaenoic acid (20:5n-3) (OR = 1.14, 95% CI = 1.01 to 1.29, Ptrend = .001) and docosapentaenoic acid (22:5n-3) (OR = 1.16, 95% CI = 1.02 to 1.33, P trend = .003), but in each case there was heterogeneity between studies (P = .022 and P < .001, respectively). There was heterogeneity in the association between docosapentaenoic acid and prostate cancer by grade of disease (P = .006); the association was statistically significant for low-grade disease but not high-grade disease. The remaining 11 fatty acids were not statistically associated with total prostate cancer risk.

    CONCLUSION: There was no strong evidence that circulating fatty acids are important predictors of prostate cancer risk. It is not clear whether the modest associations of stearic, eicosapentaenoic, and docosapentaenoic acid are causal.

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  • 26.
    Danneman, Daniela
    et al.
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Drevin, Linda
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Delahunt, Brett
    Univ Otago, Wellington Sch Med & Hlth Sci, Wellington, New Zealand..
    Samaratunga, Hemamali
    Aquesta Pathol, Brisbane, Qld, Australia.;Univ Queensland, Sch Med, Brisbane, Qld, Australia..
    Robinson, David
    Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden..
    Bratt, Ola
    Cambridge Univ Hosp, Dept Urol, Cambridge, England.;Lund Univ, Dept Translat Med, Lund, Sweden..
    Loeb, Stacy
    NYU, Dept Urol & Populat Hlth, New York, NY USA.;Manhattan Vet Affairs Med Ctr, New York, NY USA..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Egevad, Lars
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden..
    Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000-20122017Inngår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 119, nr 1, s. 50-56Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives To investigate how well the Gleason score in diagnostic needle biopsies predicted the Gleason score in a subsequent radical prostatectomy (RP) specimen before and after the 2005 International Society of Urological Pathology (ISUP) revision of Gleason grading, and if the recently proposed ISUP grades 1-5 (corresponding to Gleason scores 6, 3 + 4, 4 + 3, 8 and 9-10) better predict the RP grade. Patients and Methods All prostate cancers diagnosed in Sweden are reported to the National Prostate Cancer Register (NPCR). We analysed the Gleason scores and ISUP grades from the diagnostic biopsies and the RP specimens in 15 598 men in the NPCR who: were diagnosed between 2000 and 2012 with clinical stage T1-2 M0/X prostate cancer on needle biopsy; were aged <= 70 years; had serum PSA concentration of < 20 ng/mL; and underwent a RP < 6 months after diagnosis as their primary treatment. Results Prediction of RP Gleason score increased from 55 to 68% between 2000 and 2012. Most of the increase occurred before 2005 (nine percentage points; P < 0.001); however, when adjusting for Gleason score and year of diagnosis in a multivariable analysis, the prediction of RP Gleason score decreased over time (odds ratio [OR] 0.98; P < 0.002). A change in the ISUP grades would have led to a decreasing agreement between biopsy and RP grades over time, from 68% in 2000 to 57% in 2012, with an OR of 0.95 in multivariable analysis (P < 0.001). Conclusion Agreement between biopsy and RP Gleason score improved from 2000 to 2012, with most of the improvement occurring before the 2005 ISUP grading revision. Had ISUP grades been used instead of Gleason score, the agreement between biopsy and RP grade would have decreased, probably because of its separation of Gleason score 7 into ISUP grades 2 and 3 (Gleason score 3 + 4 vs 4 + 3).

  • 27. Danneman, Daniela
    et al.
    Drevin, Linda
    Robinson, David
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Egevad, Lars
    Gleason inflation 1998-2011: a registry study of 97,168 men2015Inngår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 115, nr 2, s. 248-55Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To study long-term trends in Gleason grading in a nationwide population and to assess the impact of the International Society of Urological Pathology (ISUP) revision in 2005 of the Gleason system on grading practices, as in recent years there has been a shift upwards in Gleason grading of prostate cancer.

    PATIENTS AND METHODS: All newly diagnosed prostate cancers in Sweden are reported to the National Prostate Cancer Register (NPCR). In 97 168 men with a primary diagnosis of prostate cancer on needle biopsy from 1998 to 2011, Gleason score, clinical T stage (cT) and serum levels of prostate-specific antigen (s-PSA) at diagnosis were analysed.

    RESULTS: Gleason score, cT stage and s-PSA were reported to the NPCR in 97%, 99% and 99% of cases. Before and after 2005, Gleason score 7-10 was diagnosed in 52% and 57%, respectively (P < 0.001). After standardisation for cT stage and s-PSA with 1998 as baseline these tumours increased from 59% to 72%. Among low-risk tumours (stage cT1 and s-PSA 4-10 ng/mL) Gleason score 7-10 increased from 16% in 1998 to 40% in 2011 (P trend < 0.001), mean 19% and 33% before and after 2005 (P < 0.001). Among high-risk tumours (stage T3 and s-PSA 20-50 ng/mL) Gleason score 7-10 increased from 65% in 1998 to 94% in 2011 (P trend < 0.001), mean 78% and 90% before and after 2005 (P < 0.001). A Gleason score of 2-5 was reported in 27% in 1998 and 1% in 2011. Gleason score 5 decreased sharply after 2005 and Gleason score 2-4 was almost abandoned.

    CONCLUSIONS: There has been a gradual shift towards higher Gleason grading, which started before 2005 but became more evident after the ISUP 2005 revision. Among low-stage tumours reporting of Gleason score 7-10 was more than doubled during the study period. When corrected for stage migration upgrading is considerable over recent decades. This has clinical consequences for therapy decisions such as eligibility for active surveillance. Grading systems need to be as stable as possible to enable comparisons over time and to facilitate the interpretation of the prognostic impact of grade.

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  • 28.
    Egevad, Lars
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Danneman, Daniela
    Karolinska Inst, Stockholm, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Drevin, Linda
    Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
    Correlation of Gleason Score in Biopsy and Radical Prostatectomy Specimens 2000-2012-A Registry Study of 15598 Men2015Inngår i: Laboratory Investigation, ISSN 0023-6837, E-ISSN 1530-0307, Vol. 95, s. 217A-218AArtikkel i tidsskrift (Annet vitenskapelig)
  • 29. Egevad, Lars
    et al.
    Kristiansen, Anna
    Drevin, Linda
    Delahunt, Brett
    Samaratunga, Hemamali
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Prognostic Significance of Prostate Cancer with Seminal Vesicle Invasion on Radical Prostatectomy: A National Registry Study2017Inngår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 30, nr Suppl. 2, s. 222A-222A, artikkel-id 896Artikkel i tidsskrift (Annet vitenskapelig)
  • 30. Egevad, Lars
    et al.
    Kristiansen, Anna
    Drevin, Linda
    Delahunt, Brett
    Samaratunga, Hemamali
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Prognostic Significance of Prostate Cancer with Seminal Vesicle Invasion on Radical Prostatectomy: A National Registry Study2017Inngår i: Laboratory Investigation, ISSN 0023-6837, E-ISSN 1530-0307, Vol. 97, s. 222A-222AArtikkel i tidsskrift (Fagfellevurdert)
  • 31.
    FitzGerald, L. M.
    et al.
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic 3004, Australia;Univ Tasmania, Menzies Inst Med Res, Canc Genet & Immunol, Hobart, Tas 7001, Australia.
    Zhao, S.
    NIEHS, Biostat & Computat Biol Branch, Res Triangle Pk, NC 27709 USA.
    Leonardson, A.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Geybels, M. S.
    Maastricht Univ, Med Ctr, GROW Sch Oncol & Dev Biol, Dept Epidemiol, NL-6211 LK Maastricht, Netherlands;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Kolb, S.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Lin, D. W.
    Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Wright, J. L.
    Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Eeles, R.
    Royal Marsden Natl Hlth Serv Fdn Trust, London, England;Royal Marsden Natl Hlth Serv Fdn Trust, Sutton SW3 6JJ, Surrey, England;Inst Canc Res, Sutton SM2 5NG, Surrey, England.
    Kote-Jarai, Z.
    Inst Canc Res, Sutton SM2 5NG, Surrey, England.
    Govindasami, K.
    Inst Canc Res, Sutton SM2 5NG, Surrey, England.
    Giles, G. G.
    Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Carlton, Vic 3053, Australia;Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic 3004, Australia.
    Southey, M. C.
    Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3010, Australia.
    Schleutker, J.
    Turku Univ Hosp, Dept Med Genet, Tuch Microbiol & Genet, Turku 20520, Finland;Univ Turku, Dept Med Biochem & Genet, Inst Biomed, Turku 20014, Finland.
    Tammela, T. L.
    Tampere Univ Hosp, Dept Urol, Tampere 33521, Finland;Univ Tampere, Prostate Canc Res Ctr, Sch Med, Tampere 33100, Finland.
    Sipeky, C.
    Univ Turku, Dept Med Biochem & Genet, Inst Biomed, Turku 20014, Finland.
    Penney, K. L.
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA;Brigham & Womens Hosp, Dept Med, Charming Div Network Med, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Stampfer, M. J.
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA;Brigham & Womens Hosp, Dept Med, Charming Div Network Med, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
    Gronberg, H.
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
    Wiklund, F.
    Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci, S-90187 Umea, Sweden.
    Hugosson, J.
    Univ Goteborgs, Inst Clin Sci, Dept Urol, S-40530 Goteborgs, Sweden.
    Karyadi, D. M.
    NHGRI, NIH, Bethesda, MD 20854 USA.
    Ostrander, E. A.
    NHGRI, NIH, Bethesda, MD 20854 USA.
    Feng, Z.
    MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
    Stanford, J. L.
    Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: An analysis of 12,082 prostate cancer cases2018Inngår i: Prostate Cancer and Prostatic Diseases, ISSN 1365-7852, E-ISSN 1476-5608, Vol. 21, nr 2, s. 228-237Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Prostate cancer (PCa) is a leading cause of mortality and genetic factors can influence tumour aggressiveness. Several germline variants have been associated with PCa-specific mortality (PCSM), but further replication evidence is needed.

    Methods: Twenty-two previously identified PCSM-associated genetic variants were genotyped in seven PCa cohorts (12,082 patients; 1544 PCa deaths). For each cohort, Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for risk of PCSM associated with each variant. Data were then combined using a meta-analysis approach.

    Results Fifteen SNPs were associated with PCSM in at least one of the seven cohorts. In the meta-analysis, after adjustment for clinicopathological factors, variants in the MGMT (rs2308327; HR 0.90; p-value = 3.5 x 10(-2)) and IL4 (rs2070874; HR 1.22; p-value = 1.1 x 10(-3)) genes were confirmed to be associated with risk of PCSM. In analyses limited to men diagnosed with local or regional stage disease, a variant in AKT1, rs2494750, was also confirmed to be associated with PCSM risk (HR 0.81; p-value = 3.6 x 10(-2)).

    Conclusions: This meta-analysis confirms the association of three genetic variants with risk of PCSM, providing further evidence that genetic background plays a role in PCa-specific survival. While these variants alone are not sufficient as prognostic biomarkers, these results may provide insights into the biological pathways modulating tumour aggressiveness.

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  • 32.
    Fridriksson, Jón Örn
    et al.
    Umeå Univ, Umeå, Sweden.
    Folkvaljon, Yasin
    Reg Canc Ctr Uppsala Örebro, Uppsala, Sweden.
    Lundström, Karl-Johan
    Umeå Univ, Umeå, Sweden.
    Robinson, David
    Umeå Univ, Umeå, Sweden;Ryhov Hosp, Jönköping, Sweden.
    Carlsson, Stefan
    Karolinska Inst, Stockholm, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umeå Univ, Umeå, Sweden.
    Long-term adverse effects after retropubic and robot-assisted radical prostatectomy: Nationwide, population-based study2017Inngår i: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 116, nr 4, s. 500-506Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Surgery for prostate cancer is associated with adverse effects. We studied long-term risk of adverse effects after retropubic (RRP) and robot-assisted radical prostatectomy (RARP).

    METHODS: In the National Prostate Cancer Register of Sweden, men who had undergone radical prostatectomy (RP) between 2004 and 2014 were identified. Diagnoses and procedures indicating adverse postoperative effects were retrieved from the National Patient Register. Relative risk (RR) of adverse effects after RARP versus RRP was calculated in multivariable analyses adjusting for year of surgery, hospital surgical volume, T stage, Gleason grade, PSA level at diagnosis, patient age, comorbidity, and educational level.

    RESULTS: A total of 11 212 men underwent RRP and 8500 RARP. Risk of anastomotic stricture was lower after RARP than RRP, RR for diagnoses 0.51 (95%CI = 0.42-0.63) and RR for procedures 0.46 (95%CI = 0.38-0.55). Risk of inguinal hernia was similar after RARP and RRP but risk of incisional hernia was higher after RARP, RR for diagnoses 1.48 (95%CI = 1.01-2.16), and RR for procedures 1.52 (95%CI = 1.02-2.26).

    CONCLUSIONS: The postoperative risk profile for RARP and RRP was quite similar. However, risk of anastomotic stricture was lower and risk of incisional hernia higher after RARP.

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  • 33.
    Gnanapragasam, V. J.
    et al.
    Univ Cambridge, Dept Surg & Oncol, Acad Urol Grp, Box 279 S4,Cambridge Biomed Campus, Cambridge CB2 0QQ, England.;Addenbrookes Hosp, Dept Urol, Cambridge, England..
    Bratt, O.
    Lund Univ, Dept Translat Med, Div Urol Canc, Lund, Sweden..
    Muir, K.
    Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England..
    Lees, L. S.
    Singapore Gen Hosp, Dept Urol, Singapore, Singapore..
    Huang, H. H.
    Singapore Gen Hosp, Dept Urol, Singapore, Singapore..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.
    Lophatananon, A.
    Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England..
    The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study2018Inngår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 16, artikkel-id 31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background:

    The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer.

    Methods:

    We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality.

    Results:

    The PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p < 0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current three-tiered system (concordance index (C-index) 0.81 vs. 0.77, p < 0.0001). This superiority was maintained for every age group division (p < 0.0001). Also in the ethnically different Singapore cohort of 2550 men with 142 prostate cancer deaths, the CPG model outperformed the three strata categories (C-index 0.79 vs. 0.76, p < 0.0001). The model also retained superior prognostic discrimination in the treatment sub-groups: radical prostatectomy (n = 20,586), C-index 0.77 vs. 074; radiotherapy (n = 11,872), C-index 0.73 vs. 0.69; and conservative management (n = 14,950), C-index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate-risk (CPG2 vs. CPG3) and high-risk categories (CPG4 vs. CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p < 0.0001).

    Conclusions:

    This validation study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.

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  • 34.
    Gnanapragasam, Vincent J.
    et al.
    Univ Cambridge, Acad Urol Grp, Dept Surg, Box 279 S4,Cambridge Biomed Campus, Cambridge CB2 0QQ, England;Cambridge Univ Hosp NHS Trust, Dept Urol, Cambridge, England;Univ Cambridge, Cambridge Urol Translat Res & Clin Trials, Cambridge Biomed Campus, Cambridge, England.
    Barrett, Tristan
    Univ Cambridge, Dept Radiol, Cambridge, England.
    Thankapannair, Vineetha
    Cambridge Univ Hosp NHS Trust, Dept Urol, Cambridge, England.
    Thurtle, David
    Univ Cambridge, Acad Urol Grp, Dept Surg, Box 279 S4,Cambridge Biomed Campus, Cambridge CB2 0QQ, England.
    Rubio-Briones, Jose
    Fdn Inst Valenciano Oncol, Valencia, Spain.
    Dominguez-Escrig, Jose
    Fdn Inst Valenciano Oncol, Valencia, Spain.
    Bratt, Ola
    Gothenburg Univ, Sahlgrenska Acad, Gothenburg, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Muir, Kenneth
    Univ Manchester, Dept Publ Hlth & Epidemiol, Manchester, Lancs, England.
    Lophatananon, Artitaya
    Univ Manchester, Dept Publ Hlth & Epidemiol, Manchester, Lancs, England.
    Using prognosis to guide inclusion criteria, define standardised endpoints and stratify follow-up in active surveillance for prostate cancer2019Inngår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 124, nr 5, s. 758-767Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives To test whether using disease prognosis can inform a rational approach to active surveillance (AS) for early prostate cancer. Patients and methods We previously developed the Cambridge Prognostics Groups (CPG) classification, a five-tiered model that uses prostate-specific antigen (PSA), Grade Group and Stage to predict cancer survival outcomes. We applied the CPG model to a UK and a Swedish prostate cancer cohort to test differences in prostate cancer mortality (PCM) in men managed conservatively or by upfront treatment in CPG2 and 3 (which subdivides the intermediate-risk classification) vs CPG1 (low-risk). We then applied the CPG model to a contemporary UK AS cohort, which was optimally characterised at baseline for disease burden, to identify predictors of true prognostic progression. Results were re-tested in an external AS cohort from Spain. Results In a UK cohort (n = 3659) the 10-year PCM was 2.3% in CPG1, 1.5%/3.5% in treated/untreated CPG2, and 1.9%/8.6% in treated/untreated CPG3. In the Swedish cohort (n = 27 942) the10-year PCM was 1.0% in CPG1, 2.2%/2.7% in treated/untreated CPG2, and 6.1%/12.5% in treated/untreated CPG3. We then tested using progression to CPG3 as a hard endpoint in a modern AS cohort (n = 133). During follow-up (median 3.5 years) only 6% (eight of 133) progressed to CPG3. Predictors of progression were a PSA density >= 0.15 ng/mL/mL and CPG2 at diagnosis. Progression occurred in 1%, 8% and 21% of men with neither factor, only one, or both, respectively. In an independent Spanish AS cohort (n = 143) the corresponding rates were 3%, 10% and 14%, respectively. Conclusion Using disease prognosis allows a rational approach to inclusion criteria, discontinuation triggers and risk-stratified management in AS.

  • 35.
    Hammarsten, Peter
    et al.
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Josefsson, Andreas
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden.
    Thysell, Elin
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Lundholm, Marie
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Hagglof, Christina
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Iglesias-Gato, Diego
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Copenhagen, Denmark.
    Flores-Morales, Amilcar
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Copenhagen, Denmark.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Egevad, Lars
    Karolinska Univ Hosp, Dept Pathol & Cytol, Stockholm, Sweden.
    Granfors, Torvald
    Cent Hosp Vasteras, Dept Urol, Vasteras, Sweden.
    Wikstrom, Pernilla
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Bergh, Anders
    Umea Univ, Dept Med Biosci, Pathol, Umea, Sweden.
    Immunoreactivity for prostate specific antigen and Ki67 differentiates subgroups of prostate cancer related to outcome2019Inngår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 32, nr 9, s. 1310-1319Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Based on gene-expression profiles, prostate tumors can be subdivided into subtypes with different aggressiveness and response to treatment. We investigated if similar clinically relevant subgroups can be identified simply by the combination of two immunohistochemistry markers: one for tumor cell differentiation (prostate specific antigen, PSA) and one for proliferation (Ki67). This was analyzed in men with prostate cancer diagnosed at transurethral resection of the prostate 1975-1991 (n = 331) where the majority was managed by watchful waiting. Ki67 and PSA immunoreactivity was related to outcome and to tumor characteristics previously associated with prognosis. Increased Ki67 and decreased PSA were associated with poor outcome, and they provided independent prognostic information from Gleason score. A combinatory score for PSA and Ki67 immunoreactivity was produced using the median PSA and Ki67 levels as cut-off (for Ki67 the upper quartile was also evaluated) for differentiation into subgroups. Patients with PSA low/Ki67 high tumors showed higher Gleason score, more advanced tumor stage, and higher risk of prostate cancer death compared to other patients. Their tumor epithelial cells were often ERG positive and expressed higher levels of ErbB2, phosphorylated epidermal growth factor receptor (pEGF-R) and protein kinase B (pAkt), and their tumor stroma showed a reactive response with type 2 macrophage infiltration, high density of blood vessels and hyaluronic acid, and with reduced levels of caveolin-1, androgen receptors, and mast cells. In contrast, men with PSA high/Ki67 low tumors were characterized by low Gleason score, and the most favorable outcome amongst PSA/Ki67-defined subgroups. Men with PSA low/Ki67 low tumors showed clinical and tumor characteristics intermediate of the two groups above. A combinatory PSA/Ki67 immunoreactivity score identifies subgroups of prostate cancers with different epithelial and stroma phenotypes and highly different outcome but the clinical usefulness of this approach needs to be validated in other cohorts.

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  • 36. Hägglöf, Christina
    et al.
    Hammarsten, Peter
    Strömvall, Kerstin
    Egevad, Lars
    Josefsson, Andreas
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Granfors, Torvald
    Bergh, Anders
    TMPRSS2-ERG expression predicts prostate cancer survival and associates with stromal biomarkers.2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 2, artikkel-id e86824Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The TMPRSS2-ERG gene fusion is found in approximately half of all prostate cancers. The functional and prognostic significance of TMPRSS2-ERG is, however, not fully understood. Based on a historical watchful waiting cohort, an association between TMPRSS2-ERG, evaluated as positive immune staining, and shorter survival of prostate cancer patients was identified. Expression of ERG was also associated with clinical markers such as advanced tumor stage, high Gleason score, presence of metastasis and prognostic tumor cell markers such as high Ki67, pEGFR and pAkt. Novel associations between TMPRSS2-ERG and alterations in the tumor stroma, for example, increased vascular density, hyaluronan and PDGFRβ and decreased Caveolin-1, all known to be associated with an aggressive disease, were found. The present study suggests that the TMPRSS2-ERG fusion gene is associated with a more aggressive prostate cancer phenotype, supported by changes in the tumor stroma.

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  • 37.
    Häggström, Christel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Biobank Res, S-90185 Umea, Sweden;Umea Univ, Dept Publ Hlth & Clin Med, Nutr Res, Umea, Sweden.
    Jonsson, Håkan
    Umea Univ, Dept Radiat Sci, Umea, Sweden.
    Björge, Tone
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway;Canc Registry Norway, Oslo, Norway.
    Nagel, Gabriele
    Ulm Univ, Inst Epidemiol & Med Biometry, Ulm, Germany;Agcy Prevent & Social Med, Vorarlberg Canc Registry, Bregenz, Aks, Austria.
    Manjer, Jonas
    Lund Univ, Skane Univ Hosp, Dept Surg, Malmo, Sweden.
    Ulmer, Hanno
    Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Innsbruck, Austria.
    Drake, Isabel
    Lund Univ, Dept Clin Sci Malmo, Lund, Sweden.
    Ghaderi, Sara
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
    Lang, Alois
    Agcy Prevent & Social Med, Vorarlberg Canc Registry, Bregenz, Aks, Austria.
    Engeland, Anders
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway;Norwegian Inst Publ Hlth, Bergen, Norway.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stocks, Tanja
    Lund Univ, Dept Clin Sci Lund, Lund, Sweden.
    Linear age-course effects on the associations between body mass index, triglycerides, and female breast and male liver cancer risk: An internal replication study of 800,000 individuals2020Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, nr 1, s. 58-67Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Apart from the consistently observed differential association between obesity and breast cancer risk by menopausal status, the associations between obesity and other metabolic imbalances with risks of cancers have not been systematically investigated across the age-course. We created two random 50-50% cohorts from six European cohorts comprising 813,927 individuals. In the "discovery cohort", we used Cox regression with attained age as time-scale and tested interactions between body mass index (BMI), blood pressure, plasma glucose, triglycerides and cholesterol, and attained age in relation to cancer risk. Results with a p-value below 0.05 were additionally tested in the "replication cohort" where a replicated result was considered evidence of a linear interaction with attained age. These findings were investigated by flexible parametric survival models for any age-plateaus in their shape of associations with cancer risk across age. Consistent with other studies, BMI was negatively related to breast cancer risk (n cases = 11,723) among younger (premenopausal) women. However, the association remained negative for several years after menopause and, although gradually weakening over age, the association became positive only at 62 years of age. This linear and positive age-interaction was also found for triglycerides and breast cancer, and for BMI and triglycerides in relation to liver cancer among men (n cases = 444). These findings are unlikely to be due to chance owing to the replication. The linear age-interactions in breast cancer may suggest an influence by other age-related factors than menopause; however, further investigation of age-related effect modifiers in both breast and liver cancer is needed.

  • 38.
    Häggström, Christel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.;Umea Univ, Dept Biobank Res, S-90185 Umea, Sweden..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Stocks, Tanja
    Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.;Lund Univ, Dept Clin Sci Diabet & Cardiovasc Dis, Genet Epidemiol, Lund, Sweden..
    Garmo, Hans
    Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden.;Kings Coll London, Fac Life Sci & Med, Div Canc Studies, London, England..
    Holmberg, Lars
    Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden.;Kings Coll London, Fac Life Sci & Med, Div Canc Studies, London, England..
    Van Hemelrijck, Mieke
    Kings Coll London, Fac Life Sci & Med, Div Canc Studies, London, England.;Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Interpretation of conventional survival analysis and competing-risk analysis: an example of hypertension and prostate cancer2016Inngår i: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, nr 6, s. 850-852Artikkel i tidsskrift (Annet vitenskapelig)
    Fulltekst (pdf)
    fulltext
  • 39. Häggström, Christel
    et al.
    Stocks, Tanja
    Nagel, Gabriele
    Manjer, Jonas
    Bjørge, Tone
    Hallmans, Göran
    Engeland, Anders
    Ulmer, Hanno
    Lindkvist, Björn
    Selmer, Randi
    Concin, Hans
    Tretli, Steinar
    Jonsson, Håkan
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations2014Inngår i: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 25, nr 6, s. 823-828Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes.

    METHODS: In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, cholesterol, and triglycerides were collected from 285,040 men. Risks of prostate cancer diagnosis, prostate cancer death, and death from other causes were calculated by use of competing risk analysis for men with normal (bottom 84%) and high (top 16%) levels of each factor, and a composite score.

    RESULTS: During a mean follow-up period of 12 years, 5,893 men were diagnosed with prostate cancer, 1,013 died of prostate cancer, and 26,328 died of other causes. After 1996, when prostate-specific antigen testing was introduced, men up to age 80 years with normal metabolic levels had 13% risk of prostate cancer, 2% risk of prostate cancer death, and 30% risk of death from other causes, whereas men with metabolic aberrations had corresponding risks of 11%, 2%, and 44%.

    CONCLUSIONS: In contrast to recent studies using conventional survival analysis, in a real-world scenario taking risk of competing events into account, men with metabolic aberrations had lower risk of prostate cancer diagnosis, similar risk of prostate cancer death, and substantially higher risk of death from other causes compared with men who had normal metabolic levels.

  • 40.
    Häggström, Christel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Biobank Res, S-90185 Umea, Sweden;Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Rowley, Mark
    Kings Coll London, Inst Math & Mol Biomed, London, England;Saddle Point Sci, London, England.
    Coolen, Anthony C. C.
    Kings Coll London, Inst Math & Mol Biomed, London, England.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Heterogeneity in risk of prostate cancer: A Swedish population-based cohort study of competing risks and Type 2 diabetes mellitus2018Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, nr 8, s. 1868-1875Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Most previous studies of prostate cancer have not taken into account that men in the studied populations are also at risk of competing event, and that these men may have different susceptibility to prostate cancer risk. The aim of our study was to investigate heterogeneity in risk of prostate cancer, using a recently developed latent class regression method for competing risks. We further aimed to elucidate the association between Type 2 diabetes mellitus (T2DM) and prostate cancer risk, and to compare the results with conventional methods for survival analysis. We analysed the risk of prostate cancer in 126,482 men from the comparison cohort of the Prostate Cancer Data base Sweden (PCBaSe) 3.0. During a mean follow-up of 6years 6,036 men were diagnosed with prostate cancer and 22,393 men died. We detected heterogeneity in risk of prostate cancer with two distinct latent classes in the study population. The smaller class included 9% of the study population in which men had a higher risk of prostate cancer and the risk was stronger associated with class membership than any of the covariates included in the study. Moreover, we found no association between T2DM and risk of prostate cancer after removal of the effect of informative censoring due to competing risks. The recently developed latent class for competing risks method could be used to provide new insights in precision medicine with the target to classify individuals regarding different susceptibility to a particular disease, reaction to a risk factor or response to treatment.

    Fulltekst (pdf)
    fulltext
  • 41.
    Häggström, Christel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.; Umea Univ, Dept Biobank Res, S-90185 Umea, Sweden..
    Van Hemelrijck, Mieke
    Kings Coll London, Div Canc Studies, Fac Life Sci & Med, London, England.;Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Med Prod Agcy, Dept Sci Support, Uppsala, Sweden..
    Robinson, David
    Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Grundmark, Birgitta
    Med Prod Agcy, Dept Sci Support, Uppsala, Sweden.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Div Canc Studies, Fac Life Sci & Med, London, England.
    Gudbjörnsdottir, Soffia
    Gothenburg Univ, Sahlgrenska Univ Hosp, Dept Med, Gothenburg, Sweden..
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Kings Coll London, Div Canc Studies, Fac Life Sci & Med, London, England.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
    Prospective study of Type 2 diabetes mellitus, anti-diabetic drugs and risk of prostate cancer2017Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, nr 3, s. 611-617Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer; however, if this decrease is related to the use of anti-diabetic drugs is unknown. We prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden 3.0, with data on T2DM, use of metformin, sulfonylurea and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders. The study consisted of 612,846 men, mean age 72 years (standard deviation; SD=9 years), out of whom 25,882 men were diagnosed with prostate cancer during follow up, mean time of 5 years (SD=3 years). Men with more than 1 year's duration of T2DM had a decreased risk of prostate cancer compared to men without T2DM (HR=0.85, 95% CI=0.82-0.88) but among men with T2DM, those on metformin had no decrease (HR=0.96, 95% CI=0.77-1.19), whereas men on insulin (89%) or sulfonylurea (11%) had a decreased risk (HR=0.73, 95% CI=0.55-0.98), compared to men with T2DM not on anti-diabetic drugs. Men with less than 1 year's duration of T2DM had no decrease in prostate cancer risk (HR=1.11, 95% CI=0.95-1.31). Our results gave no support to the hypothesis that metformin protects against prostate cancer as recently proposed. However, our data gave some support to an inverse association between T2DM severity and prostate cancer risk.

    What's new? Although Type 2 diabetes mellitus (T2DM) increases the risk of several cancers, multiple studies point toward a significantly inverse relationship between T2DM and prostate cancer risk in men. Use of the anti-diabetic drug metformin is suspected of underlying the association. In this prospective study in Sweden, however, metformin failed to decrease the risk of prostate cancer. By comparison, risk was decreased in association with the use of insulin or sulfonylurea. These findings add some support to an inverse association between T2DM severity and prostate cancer risk.

    Fulltekst (pdf)
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  • 42. Jan, Michael
    et al.
    Bonn, Stephanie E
    Sjölander, Arvid
    Wiklund, Fredrik
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Holmberg, Erik
    Grönberg, Henrik
    Bälter, Katarina
    The roles of stress and social support in prostate cancer mortality2016Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, nr 1, s. 47-55Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: This study aimed to evaluate the association between perceived stress, social support, disease progression and mortality in a nationwide population-based cohort of men with prostate cancer.

    MATERIALS AND METHODS: The study surveyed 4105 Swedish men treated for clinically localized prostate cancer regarding stress, grief, sleep habits and social support. Associations between these factors and mortality were assessed using multivariate Cox regression analysis.

    RESULTS: Men with the highest levels of perceived stress had a statistically significantly increased rate of prostate cancer-specific mortality compared with men with low stress levels (hazard ratio 1.66, 95% confidence interval 1.05-2.63). Men with high stress levels also had a high frequency of grieving and sleep loss. They also had fewer people with whom to share their emotional problems and felt an inability to share most of their problems with partners, friends and family.

    CONCLUSIONS: This study contributes to the growing field of psychosocial quality of life research in men with prostate cancer. The findings show a significant association between prostate cancer-specific mortality and perceived stress in patients initially diagnosed with localized, non-metastatic prostate cancer. Significant associations between perceived stress and various psychosocial factors were also seen. The findings of this study could prove useful to target interventions to improve quality of life in men with prostate cancer.

    Fulltekst (pdf)
    fulltext
  • 43.
    Jansson, Fredrik
    et al.
    Karolinska Inst, Stockholm, Sweden;Danderyd Hosp, Stockholm, Sweden.
    Drevin, Linda
    Reg Canc Ctr, Uppsala, Sweden.
    Frisell, Thomas
    Karolinska Inst, Stockholm, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Uppsala Univ Hosp, Uppsala, Sweden.
    Bratt, Ola
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden.
    Akre, Olof
    Karolinska Inst, Stockholm, Sweden;Karolinska Univ Hosp, Solna, Sweden.
    Concordance of Non-Low-Risk Disease Among Pairs of Brothers With Prostate Cancer2018Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 36, nr 18, s. 1847-1852Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Prostate cancer among first-degree relatives is a strong risk factor for diagnosis of prostate cancer, and the contribution of heritable factors in prostate cancer etiology is high. We investigated how the concordance of non-low-risk prostate cancer among brothers is affected by their genetic relation.

    Methods:We identified 4,262 pairs of brothers with prostate cancer in the Prostate Cancer Database Sweden. Their cancers were categorized as low risk (Gleason score 6; clinical stage T1-2, Nx/N0, Mx/M0; and prostate-specific antigen 10 ng/mL) or non-low risk. The odds ratio (OR) for concordance of non-low-risk cancer was calculated with logistic regression for the different types of fraternity (monozygotic twins, dizygotic twins, full brothers, and half-brothers)

    Results: Among monozygotic twins who both were diagnosed with prostate cancer, the OR for both brothers being in the non-low-risk category was 3.82 (95% CI, 0.99 to 16.72) after adjusting for age and year of diagnosis. Among full brothers, the corresponding adjusted OR was 1.21 (95% CI, 1.04 to 1.39). When the analysis was restricted to brothers who both were diagnosed within 4 years, the results were similar.

    Conclusion: Non-low-risk prostate cancer has a heritable pattern suggesting shared genetic factors, with the highest concordance among monozygotic twins. Our results suggest that a man whose brother has been diagnosed with a non-low-risk prostate cancer is at a clinically relevant increased risk of developing an aggressive prostate cancer himself.

  • 44. Jonsson, Pär
    et al.
    Wuolikainen, Anna
    Thysell, Elin
    Chorell, Elin
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ Hosp, Dept Surg & Perioperat Sci, Urol & Androl, S-90187 Umeå, Sweden.
    Wikström, Pernilla
    Antti, Henrik
    Constrained randomization and multivariate effect projections improve information extraction and biomarker pattern discovery in metabolomics studies involving dependent samples.2015Inngår i: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 11, nr 6, s. 1667-1678Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Analytical drift is a major source of bias in mass spectrometry based metabolomics confounding interpretation and biomarker detection. So far, standard protocols for sample and data analysis have not been able to fully resolve this. We present a combined approach for minimizing the influence of analytical drift on multivariate comparisons of matched or dependent samples in mass spectrometry based metabolomics studies. The approach is building on a randomization procedure for sample run order, constrained to independent randomizations between and within dependent sample pairs (e.g. pre/post intervention). This is followed by a novel multivariate statistical analysis strategy allowing paired or dependent analyses of individual effects named OPLS-effect projections (OPLS-EP). We show, using simulated data that OPLS-EP gives improved interpretation over existing methods and that constrained randomization of sample run order in combination with an appropriate dependent statistical test increase the accuracy and sensitivity and decrease the false omission rate in biomarker detection. We verify these findings and prove the strength of the suggested approach in a clinical data set consisting of LC/MS data of blood plasma samples from patients before and after radical prostatectomy. Here OPLS-EP compared to traditional (independent) OPLS-discriminant analysis (OPLS-DA) on constrained randomized data gives a less complex model (3 versus 5 components) as well a higher predictive ability (Q2 = 0.80 versus Q2 = 0.55). We explain this by showing that paired statistical analysis detects 37 unique significant metabolites that were masked for the independent test due to bias, including analytical drift and inter-individual variation.

    Fulltekst (pdf)
    fulltext
  • 45.
    Kinsella, Netty
    et al.
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.;Royal Marsden Hosp, Dept Urol, London, England..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Cahill, Declan
    Royal Marsden Hosp, Dept Urol, London, England..
    Brown, Christian
    Kings Coll Hosp London, Dept Urol, London, England..
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bratt, Ola
    Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden..
    Carlsson, Sigrid
    Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Urol, Gothenburg, Sweden.;Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA.;Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA..
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.;Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Factors Influencing Men's Choice of and Adherence to Active Surveillance for Low-risk Prostate Cancer: A Mixed-method Systematic Review2018Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 3, s. 261-280Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Context: Despite support for active surveillance (AS) as a first treatment choice for men with low-risk prostate cancer (PC), this strategy is largely underutilised.

    Objective: To systematically review barriers and facilitators to selecting and adhering to AS for low-risk PC.

    Evidence acquisition: We searched PsychINFO, PubMed, Medline 2000-now, Embase, CINAHL, and Cochrane Central databases between 2002 and 2017 using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The Purpose, Respondents, Explanation, Findings and Significance (PREFS) and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) quality criteria were applied. Forty-seven studies were identified.

    Evidence synthesis: Key themes emerged as factors influencing both choice and adherence to AS: (1) patient and tumour factors (age, comorbidities, knowledge, education, socioeconomic status, family history, grade, tumour volume, and fear of progression/side effects); (2) family and social support; (3) provider (speciality, communication, and attitudes); (4) healthcare organisation (geography and type of practice); and (5) health policy (guidelines, year, and awareness).

    Conclusions: Many factors influence men's choice and adherence to AS on multiple levels. It is important to learn from the experience of other chronic health conditions as well as from institutions/countries that are making significant headway in appropriately recruiting men to AS protocols, through standardised patient information, clinician education, and nationally agreed guidelines, to ultimately decrease heterogeneity in AS practice.

    Patient summary: We reviewed the scientific literature for factors affecting men's choice and adherence to active surveillance (AS) for low-risk prostate cancer. Our findings suggest that the use of AS could be increased by addressing a variety of factors such as information, psychosocial support, clinician education, and standardised guidelines. 

  • 46. Kristiansen, Anna
    et al.
    Drevin, Linda
    Uppsala University Hospital.
    Delahunt, Brett
    Samaratunga, Hemamali
    Robinson, David
    Franck Lissbrant, Ingela
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci PS Urol & Androl, Umeå, Sweden.
    Egevad, Lars
    Prognostic significance and biopsy characteristics of prostate cancer with seminal vesicle invasion on radical prostatectomy: a nationwide population-based study.2017Inngår i: Pathology (Sydney), ISSN 0031-3025, E-ISSN 1465-3931, Vol. 49, nr 7, s. 715-720, artikkel-id S0031-3025(17)30323-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The objective of this study was to evaluate the prognostic significance of seminal vesicle invasion (SVI, pT3b) compared with extraprostatic extension (EPE) alone (pT3a) after radical prostatectomy, and to correlate pre-operative biopsy pathology with SVI and EPE. The National Prostate Cancer Register includes all prostate cancers diagnosed in Sweden. We analysed 4063 cases with stage category pT3a and 1371 cases with pT3b at radical prostatectomy between 2000 and 2012. Associations between pT3a and pT3b and progression were evaluated and adjusted for year, age, biopsy grade and s-PSA. Needle biopsy findings in these stages were compared. Patients with pT3b (n=1371) had a higher risk of death from prostate cancer (HR 2.3, 95% CI 1.5-3.3, p<0.001) and death from any cause (HR 1.5, 95% CI 1.2-1.8, p<0.001) than those with pT3a (n=4063). They were also more likely to be treated with post-operative radiotherapy (HR 1.5, 95% CI 1.4-1.7, p<0.001) or androgen deprivation therapy (HR 3.0, 95% CI 2.5-3.7, p<0.001), indicating clinical progression. Yet, disease-specific survival of patients with stage pT3b was 94% after 6 years. Median cancer extent in pre-operative biopsies of pT3a and pT3b was 14 and 24 mm (p<0.001), number of positive cores was four and five, (p<0.001) and biopsy Gleason score was 8-10 in 11.6% and 27.3%, respectively (p<0.001). SVI of prostate cancer is associated with worse outcome after radical prostatectomy than EPE alone. However, few patients with SVI die within 6 years from surgery, suggesting that radical prostatectomy may be curative in locally advanced cancers.

  • 47.
    Li, Weiqiang
    et al.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Middha, Mridu
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Bicak, Mesude
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Sjoberg, Daniel D.
    Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
    Vertosick, Emily
    Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
    Dahlin, Anders
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Häggström, Christel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umeå Univ, Dept Biobank Res, Umeå, Sweden.
    Hallmans, Goran
    Umea Univ, Dept Publ Hlth & Clin Med, Nutr Res, Umea, Sweden.
    Ronn, Ann-Charlotte
    Karolinska Univ Hosp, Clin Res Ctr, Huddinge, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Ulmert, David
    Sloan Kettering Inst, Mol Pharmacol Program, New York, NY USA.
    Lilja, Hans
    Mem Sloan Kettering Canc Ctr, Dept Lab Med, New York, NY 10065 USA;Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA;Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA;Univ Oxford, Nuffield Dept Surg Sci, Oxford, England;Lund Univ, Dept Translat Med, Malmo, Sweden.
    Klein, Robert J.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Genome-wide Scan Identifies Role for AOX1 in Prostate Cancer Survival2018Inngår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 6, s. 710-719Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Most men diagnosed with prostate cancer have low-risk cancers. How to predict prostate cancer progression at the time of diagnosis remains challenging. Objective: To identify single nucleotide polymorphisms (SNPs) associated with death from prostate cancer. Design, setting, and participants: Blood samples from 11 506 men in Sweden were collected during 1991-1996. Of these, 1053 men were diagnosed with prostate cancer and 245 died from the disease. Stage and grade at diagnosis and outcome information were obtained, and DNA from all cases was genotyped. Outcome measurements and statistical analysis: A total of 6 126 633 SNPs were tested for association with prostate-cancer-specific survival time using a Cox proportional hazard model, adjusted for age, stage, and grade at diagnosis. A value of 1 x 10(-6) was used as suggestive significance threshold. Positive candidate SNPs were tested for association with gene expression using expression quantitative trait locus analysis. Results and limitations: We found 12 SNPs at seven independent loci associated with prostate-cancerspecific survival time. One of 6 126 633 SNPs tested reached genome-wide significance (p < 5 x 10(-8)) and replicated in an independent cohort: rs73055188 (p = 5.27 x 10(-9), per-allele hazard ratio [HR] = 2.27, 95% confidence interval [CI] 1.72-2.98) in the AOX1 gene. A second SNP reached a suggestive level of significance (p <1 x 10(-6)) and replicated in an independent cohort: rs2702185 (p = 7.1 x 10(-7), per-allele HR = 2.55, 95% CI = 1.76-3.69) in the SMG7 gene. The SNP rs73055188 is correlated with AOX1 expression levels, which is associated with biochemical recurrence of prostate cancer in independent cohorts. This association is yet to be validated in other ethnic groups. Conclusions: The SNP rs73055188 at the AOX1 locus is associated with prostate-cancer-specific survival time, and AOX1 gene expression level is correlated with biochemical recurrence of prostate cancer. Patient summary: We identify two genetic markers that are associated with prostate-cancer-specific survival time.

  • 48.
    Licciardello, Marco P.
    et al.
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Inst Canc Res, Canc Res UK Canc Therapeut Unit, London, England..
    Ringler, Anna
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Markt, Patrick
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Univ Innsbruck Hosp, Dept Pharm, Innsbruck, Austria..
    Klepsch, Freya
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Chem Comp Grp Inc, Cologne, Germany..
    Lardeau, Charles-Hugues
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Austrian Acad Sci, CeMM Res Ctr Mol Med, Christian Doppler Lab Chem Epigenet & Anti Infect, Vienna, Austria..
    Sdelci, Sara
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Schirghuber, Erika
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Austrian Acad Sci, CeMM Res Ctr Mol Med, Christian Doppler Lab Chem Epigenet & Anti Infect, Vienna, Austria..
    Mueller, Andre C.
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Caldera, Michael
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Wagner, Anja
    Med Univ Vienna, Dept Pediat & Adolescent Med, Christian Doppler Lab Mol Stress Res Peritoneal D, Vienna, Austria..
    Herzog, Rebecca
    Med Univ Vienna, Dept Pediat & Adolescent Med, Christian Doppler Lab Mol Stress Res Peritoneal D, Vienna, Austria..
    Penz, Thomas
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Schuster, Michael
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Boidol, Bernd
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Austrian Acad Sci, CeMM Res Ctr Mol Med, Christian Doppler Lab Chem Epigenet & Anti Infect, Vienna, Austria..
    Duernberger, Gerhard
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Gregor Mendel Inst, Vienna, Austria..
    Folkvaljon, Yasin
    Umea Univ Hosp, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ Hosp, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.
    Ivanov, Vladimir
    Enamine Ltd, Kiev, Ukraine..
    Colinge, Jacques
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Univ Montpellier, Fac Med, Montpellier, France.;Inst Reg Canc Montpellier, INSERM U1194, Inst Rech Cancerol Montpellier, Montpellier, France..
    Bock, Christoph
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Med Univ Vienna, Dept Lab Med, Vienna, Austria.;Max Planck Inst Informat, Saarland Informat Campus, Saarbrucken, Germany..
    Kratochwill, Klaus
    Med Univ Vienna, Dept Pediat & Adolescent Med, Christian Doppler Lab Mol Stress Res Peritoneal D, Vienna, Austria..
    Menche, Joerg
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Bennett, Keiryn L.
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria..
    Kubicek, Stefan
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria.;Austrian Acad Sci, CeMM Res Ctr Mol Med, Christian Doppler Lab Chem Epigenet & Anti Infect, Vienna, Austria..
    A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor2017Inngår i: Nature Chemical Biology, ISSN 1552-4450, E-ISSN 1552-4469, Vol. 13, nr 7, s. 771-778Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Approved drugs are invaluable tools to study biochemical pathways, and further characterization of these compounds may lead to repurposing of single drugs or combinations. Here we describe a collection of 308 small molecules representing the diversity of structures and molecular targets of all FDA-approved chemical entities. The CeMM Library of Unique Drugs (CLOUD) covers prodrugs and active forms at pharmacologically relevant concentrations and is ideally suited for combinatorial studies. We screened pairwise combinations of CLOUD drugs for impairment of cancer cell viability and discovered a synergistic interaction between flutamide and phenprocoumon (PPC). The combination of these drugs modulates the stability of the androgen receptor (AR) and resensitizes AR-mutant prostate cancer cells to flutamide. Mechanistically, we show that the AR is a substrate for gamma-carboxylation, a post-translational modification inhibited by PPC. Collectively, our data suggest that PPC could be repurposed to tackle resistance to antiandrogens in prostate cancer patients.

  • 49.
    Lissbrant, Ingela Franck
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Oncol, Gothenburg, Sweden.
    Ventimiglia, Eugenio
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Osped San Raffaele, IRCCS, URI, Div Expt Oncol, Unit Urol, Milan, Italy.
    Robinson, David
    Ryhov Cty Hosp, Dept Urol, Jönköping, Sweden.
    Törnblom, Magnus
    Visby Cty Hosp, Dept Surg, Visby, Sweden.
    Hjalm-Eriksson, Marie
    Capio St Gorans Hosp, Dept Surg, Stockholm, Sweden; Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Lambe, Mats
    Uppsala Univ Hosp, Reg Canc Ctr, Uppsala, Sweden.
    Folkvaljon, Yasin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Nationwide population-based study on the use of novel antiandrogens in men with prostate cancer in Sweden2018Inngår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, nr 2, s. 143-150Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The aim of this study was to examine the use of abiraterone and enzalutamide, two oral novel antiandrogens (NOVAs), in men with prostate cancer (PCa) in Sweden.

    Materials and methods: This cross-sectional study investigated filled prescriptions for NOVAs recorded in the Swedish Prescribed Drug Register between July 2015 and April 2016. Associations between age, comorbidity, educational level, marital status and county of residence and filled prescriptions were analyzed in the National Prostate Cancer Register (NPCR) and other health population-based registers, using multivariable logistic regression.

    Results: Of 91,209 men, 1650 (2%) had at least one prescription filled for NOVAs, of whom 1350 (82%) had high-risk or metastatic PCa at diagnosis.. Of 1914 men with M1 disease and a high probability of castration-resistant prostate cancer (CRPC), 22% had a prescription for NOVAs at a median 3 years after the date of diagnosis. At multivariable logistic regression analysis,, the likelihood of NOVA use was lower in older men [age >80 vs <70 years: odds ratio (OR) 0.23, 95% confidence interval (CI) 0.15–0.35] and in men with lower educational level (high vs low education: OR 1.64, 95% CI 1.23–2.20). There was up to a five-fold difference in the use of NOVAs between county councils.

    Conclusions: Less than one-third of potentially eligible men with CRPC received NOVAs in 2015–2016. There were large differences in use according to age and region of residence, indicating that efforts are needed to improve equal access to novel cancer drugs.

    Fulltekst (pdf)
    fulltext
  • 50.
    Loeb, Stacy
    et al.
    NYU, Dept Urol & Populat Hlth, New York, NY USA;Manhattan Vet Affairs Med Ctr, New York, NY USA.
    Cazzaniga, Walter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Univ Vita Salute San Raffaele, IRCCS Osped San Raffaele, Unit Urol URI, Expt Oncol, Milan, Italy.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Opioid Use after Radical Prostatectomy: Nationwide, Population Based Study in Sweden2020Inngår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 203, nr 1, s. 145-150Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: North American studies have revealed that about 3% to 7% of opioid naïve surgical patients transition to chronic opioid use after a single prescription. We examined the risk of chronic opioid use following radical prostatectomy using nationwide Swedish data.

    MATERIALS AND METHODS: A total of 25,703 men in the National Prostate Cancer Register of Sweden who underwent radical prostatectomy were linked to the Prescribed Drug Register. Opioid use was assessed at 3 times, including baseline (13 months to 1 month preoperatively), perioperatively (1 month before and after) and postoperatively (1 to 12 months). Multivariable logistic regression was done to identify predictors of new late use (1 or more opioid prescriptions in 3 consecutive months more than 2 months after surgery).

    RESULTS: Overall 16,368 men (64%) filled an opioid prescription during the 13 months before or after surgery. The use of strong opioids increased with time and the use of weak opioids decreased. Of the men 1.9% had opioid prescriptions during the baseline period, followed by a spike to 59% around the time surgery, which sharply decreased in month 2 postoperatively. However, thereafter the proportion of men with opioid prescriptions remained slightly higher at 2.2% compared to the baseline before radical prostatectomy. Of chronic late users 57% were previous users and 43% were new chronic users. Higher cancer risk category, greater comorbidity, unmarried status and low educational level were associated with the risk of new chronic opioid use.

    CONCLUSIONS: Slightly more than half of male Swedish patients filled an opioid prescription after radical prostatectomy and less than 1% became chronic opioid users. These rates are lower than in previous studies of postoperative opioid use from North America.

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