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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 Therapy2017Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, nr 3, s. 330-336Artikel i tidskrift (Refereegranskat)
    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.
    Akre, Olof
    et al.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Garmo, Hans
    Regional Oncological Center, Uppsala, Sweden.
    Adolfsson, Jan
    Oncological Center, CLINTEC Department, Karolinska Institutet, Stockholm, Sweden.
    Lambe, Mats
    Oncological Center, CLINTEC Department, andDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bratt, Ola
    Department of Urology, Helsingborg Hospital, Lund University, Sweden.
    Stattin, Pär
    Department of Surgical and Perioperative sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Mortality Among Men with Locally Advanced Prostate Cancer Managed with Noncurative Intent: A Nationwide Study in PCBaSe Sweden2011Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, nr 3, s. 554-563Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment.

    Objective

    To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent.

    Design, setting, and participants

    We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis.

    Measurements

    We followed up the patient cohort in the Cause of Death Register for ≤11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics.

    Results and limitations

    The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25–32%) for Gleason score (GS) 2–6, 41% (95% CI, 38–44%) for GS 7, 52% (95% CI, 47–57%) for GS 8, and 64% (95% CI, 59–69%) for GS 9–10. Even for men aged >85 yr at diagnosis with GS 8–10, PCa was a major cause of death: 42% (95% CI, 37–47%). Men with locally advanced disease and a PSA < 4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status.

    Conclusions

    The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors.

  • 3.
    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 Screening2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, nr 6, s. 961-967Artikel i tidskrift (Refereegranskat)
    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.

  • 4.
    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 Cancer2019Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, nr 4, s. 676-683Artikel i tidskrift (Refereegranskat)
    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.

  • 5.
    Bessa, Agustina
    et al.
    Kings Coll London, Sch Canc & Pharmaceut Studies, TOUR, London, England.
    Maclennan, Steven
    Univ Aberdeen, Acad Urol Unit, Aberdeen, Scotland.
    Enting, Deborah
    Kings Coll London, Sch Canc & Pharmaceut Studies, TOUR, London, England;Guys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England.
    Bryan, Richard
    Univ Birmingham, Inst Canc & Genom Sci, Birmingham, W Midlands, England.
    Josephs, Debra
    Kings Coll London, Sch Canc & Pharmaceut Studies, TOUR, London, England;Guys & St Thomas NHS Fdn Trust, Dept Med Oncol, London, England.
    Hughes, Simon
    Kings Coll London, Sch Canc & Pharmaceut Studies, TOUR, London, England;Guys & St Thomas NHS Fdn Trust, Dept Clin Oncol, London, England.
    Amery, Suzanne
    Guys & St Thomas NHS Fdn Trust, Dept Urol, London, England.
    Khan, Muhammad Shamim
    Guys & St Thomas NHS Fdn Trust, Dept Urol, London, England.
    Malde, Sachin
    Guys & St Thomas NHS Fdn Trust, Dept Urol, London, England.
    Nair, Rajesh
    Guys & St Thomas NHS Fdn Trust, Dept Urol, London, England.
    Cahill, Fidelma
    Kings Coll London, Sch Canc & Pharmaceut Studies, TOUR, London, England.
    Wylie, Harriet
    Kings Coll London, Sch Canc & Pharmaceut Studies, TOUR, London, England.
    Thurairaja, Ramesh
    Guys & St Thomas NHS Fdn Trust, Dept Urol, London, England.
    Chatterton, Kathryn
    Guys & St Thomas NHS Fdn Trust, Dept Urol, London, England.
    Kinsella, Netty
    Kings Coll London, Sch Canc & Pharmaceut Studies, TOUR, London, England;Royal Marsden NHS Fdn Trust, London, England.
    Häggström, Christel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Biobank Res, Umea, Sweden.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Studies, TOUR, London, England.
    Consensus in Bladder Cancer Research Priorities Between Patients and Healthcare Professionals Using a Four-stage Modified Delphi Method2019Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, nr 2, s. 258-259Artikel i tidskrift (Övrigt vetenskapligt)
  • 6.
    Bill-Axelson, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bratt, Ola
    Re: Screening and Prostate Cancer Mortality: Results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 Years of Follow-up2015Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 67, nr 1, s. 175-175Artikel i tidskrift (Övrigt vetenskapligt)
  • 7.
    Bill-Axelson, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Regional Cancer Center, Uppsala-Örebro, Uppsala, Sweden.
    Holmberg, Lars
    King's College London, Medical School, Division of Cancer Studies, London, UK.
    Johansson, Jan-Erik
    Adami, Hans-Olov
    Steineck, Gunnar
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Rider, Jennifer R
    Long-term Distress After Radical Prostatectomy Versus Watchful Waiting in Prostate Cancer: A Longitudinal Study from the Scandinavian Prostate Cancer Group-4 Randomized Clinical Trial2013Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 64, nr 6, s. 920-928Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Studies enumerating the dynamics of physical and emotional symptoms following prostate cancer (PCa) treatment are needed to guide therapeutic strategy. Yet, overcoming patient selection forces is a formidable challenge for observational studies comparing treatment groups.

    OBJECTIVE:

    To compare patterns of symptom burden and distress in men with localized PCa randomized to radical prostatectomy (RP) or watchful waiting (WW) and followed up longitudinally.

    DESIGN, SETTING, AND PARTICIPANTS:

    The three largest, Swedish, randomization centers for the Scandinavian Prostate Cancer Group-4 trial conducted a longitudinal study to assess symptoms and distress from several psychological and physical domains by mailed questionnaire every 6 mo for 2 yr and then yearly through 8 yr of follow-up.

    INTERVENTION:

    RP compared with WW.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

    A questionnaire was mailed at baseline and then repeatedly during follow-up with questions concerning physical and mental symptoms. Each analysis of quality of life was based on a dichotomization of the outcome (yes vs no) studied in a binomial response, generalized linear mixed model.

    RESULTS AND LIMITATIONS:

    Of 347 randomized men, 272 completed at least five questionnaires during an 8-yr follow-up period. Almost all men reported that PCa negatively influenced daily activities and relationships. Health-related distress, worry, feeling low, and insomnia were consistently reported by approximately 30-40% in both groups. Men in the RP group consistently reported more leakage, impaired erection and libido, and fewer obstructive voiding symptoms. For men in the WW group, distress related to erectile symptoms increased gradually over time. Symptom burden and distress at baseline was predictive of long-term outlook.

    CONCLUSIONS:

    Cancer negatively influenced daily activities among almost all men in both treatment groups; health-related distress was common. Trade-offs exist between physiologic symptoms, highlighting the importance of tailored treatment decision-making. Men who are likely to experience profound long-term distress can be identified early in disease management.

  • 8.
    Bill-Axelson, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Garmo, Hans
    Lambe, Mats
    Bratt, Ola
    Adolfsson, Jan
    Nyberg, Ullakarin
    Steineck, Gunnar
    Stattin, Pär
    Suicide Risk in Men with Prostate-Specific Antigen-Detected Early Prostate Cancer: A Nationwide Population-Based Cohort Study from PCBaSe Sweden2010Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, nr 3, s. 390-395Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The risk of suicide is increased among cancer patients including men with prostate cancer (PCa). However, whether this increased risk applies to men diagnosed subsequent to prostate-specific antigen (PSA) testing is not known. Objective: To assess the risk of suicide among men diagnosed with PCa subsequent to PSA testing. Design, setting, and participants: The Prostate Cancer Base Sweden (PCBaSe Sweden) database, the Swedish Cause of Death Register, and the Swedish census database were used. The PCBaSe Sweden is a merged database that includes data from the Swedish National Prostate Cancer Register (NPCR) for cases diagnosed between January 1, 1997, and December 31, 2006. The number of suicides registered for cases in the PCBaSe cohort was compared with the expected number of suicides in an age-matched general male Swedish population. Measurements: Standardised mortality ratios (SMRs) with 95% confidence intervals (CIs) were calculated for different categories of cases. Results and limitations: There were 128 suicides among the 77 439 PCa cases in the NPCR compared with an expected number of 85 (SMR: 1.5; 95% CI, 1.3-1.8). The risk of suicide was not increased for the 22 405 men with PSA-detected T1c tumours (SMR: 1.0; 95% CI, 0.6-1.5), whereas the 22 929 men with locally advanced nonmetastatic tumours (SMR: 2.2; 95% CI, 1.6-2.9) and the 8350 men with distant metastases (SMR: 2.1; 95% CI, 1.2-3.6) had statistically significant increased SMRs for suicide. Potential effects of comorbid medical and psychiatric conditions could not be investigated. Conclusions: No increased risk of committing suicide was observed among men with PCa diagnosed subsequent to PSA testing, whereas the risk was twice as high among men with locally advanced or metastatic disease, compared with an age-matched male population. (C) 2009 European Association of Urology.

  • 9. Bratt, Ola
    et al.
    Folkvaljon, Yasin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Eriksson, Marie Hjalm
    Akre, Olof
    Carlsson, Stefan
    Drevin, Linda
    Lissbrant, Ingela Franck
    Makarov, Danil
    Loeb, Stacy
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Undertreatment of Men in Their Seventies with High-risk Nonmetastatic Prostate Cancer2015Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 68, nr 1, s. 53-58Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Many elderly men with high-risk nonmetastatic prostate cancer (HRnMPCa) do not receive radical treatment, despite the high mortality associated with conservative management. Objective: To investigate how age and comorbidity affect treatment of men with HRnMPCa. Design, setting, and participants: This was an observational nationwide register study during 2001-2012. We identified 19 190 men of <80 yr of age diagnosed with HRnMPCa in the National Prostate Cancer Register of Sweden and 95 948 age-matched men without prostate cancer in the register of the total population. Outcome measurements and statistical analysis: The outcome was the proportion of men with HRnMPCa receiving radical treatment (radical prostatectomy or radiotherapy). Vital status and the Charlson comorbidity index (CCI) were obtained from nationwide registers. The 10-yr survival of men without prostate cancer, stratified by age and CCI, was used as a measure of the life expectancy of the men with prostate cancer. Results and limitations: The proportions receiving radical treatment varied with life expectancy among men younger than 70 yr, whereas use of these treatments did not match the long life expectancy of men in their seventies with CCI 0-1. Only 10% of men aged 75-80 yr with CCI 0 received radical treatment despite 52% probability of 10-yr life expectancy, compared with approximately half of the men younger than 70 yr with a similar life expectancy. The use of radical treatment for HRnMPCa increased with time in all Swedish counties, but a threefold difference between counties remained in 2009-2012 for patients aged 70-80 yr with CCI 0-1. Uncertain external validity is a study limitation, and the impact of physician versus patient preferences on treatment selection could not be assessed. Conclusions: Otherwise healthy men in their seventies with HRnMPCa were less likely to receive radical treatment than younger men with a similar life expectancy, although increasing use of radical treatment was observed during the study period. Our findings highlight the need for improved methods for clinical decision-making, including improved assessment of life expectancy. Patient summary: We performed a nationwide register study that showed that many healthy men in their seventies live for at least another 10 yr. Despite this long life expectancy, men in their seventies with high-risk nonmetastatic prostate cancer were often not treated with radical prostatectomy or radiotherapy, possibly because their life expectancy was underestimated. Our study highlights the need for improved clinical decision-making, which should incorporate an assessment of the patient's life expectancy.

  • 10.
    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)2019Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, nr 4, s. 461-466Artikel i tidskrift (Refereegranskat)
    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.

  • 11.
    Catto, James W. F.
    et al.
    Univ Sheffield, Acad Urol Unit, Sheffield, S Yorkshire, England..
    Blazeby, Jane M.
    Univ Bristol, Bristol Ctr Surg Res, Bristol, Avon, England..
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Fac Life Sci & Med, London, England..
    Hamdy, Freddie C.
    Univ Oxford, Nuffield Dept Surg Sci, Oxford, England..
    Brown, Julia
    Univ Leeds, Leeds Inst Clin Trials Res, Leeds, W Yorkshire, England..
    In Defense of Randomized Clinical Trials in Surgery: Let Us Not Forget Archie Cochrane's Legacy2017Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, nr 5, s. 820-821Artikel i tidskrift (Refereegranskat)
  • 12. Dahm, Philipp
    et al.
    N’Dow, James
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Hamdy, Freddie
    The future of randomised controlled trials in urology2014Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 66, nr 1, s. 1-3Artikel i tidskrift (Refereegranskat)
  • 13. Duchek, Milos
    et al.
    Johansson, Robert
    Jahnson, Staffan
    Mestad, Oddvar
    Hellström, Pekka
    Hellsten, Sverker
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bacillus Calmette-Guerin Is Superior to a Combination of Epirubicin and Interferon-alpha 2b in the Intravesical Treatment of Patients with Stage T1 Urinary Bladder Cancer. A Prospective, Randomized, Nordic Study2010Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, nr 1, s. 25-31Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Bacillus Calmette-Guerin (BCG) instillation is regarded as the most effective bladder-sparing treatment for patients with high-grade T1 tumours and carcinoma in situ (CIS). The major problem with this therapy is the side-effects, making maintenance therapy difficult, even impossible, in a proportion of patients. Thus, alternative schedules and drugs have been proposed. Objective: To compare BCG to the combination of epirubicin and interferon-alpha 2b as adjuvant therapy of T1 tumours. Design, setting, and participants: This is a Nordic multicenter, prospective, randomised trial in patients with primary T1 G2-G3 bladder cancer. Initial transurethral resection (TUR) was followed by a second-look resection. Patients were randomised to receive either regimen, given as induction for 6 wk followed by maintenance therapy for 2 yr. Measurements: The drugs were compared with respect to time to recurrence and progression. Also, side-effects were documented. Results and limitations: A total of 250 patients were randomised. At the primary end point, 62% were disease free in the combination arm as opposed to 73% in the BCG arm (p = 0.065). At 24 mo, there was a significant difference in favour of the BCG-treated patients (p = 0.012) regarding recurrence, although there was no difference regarding progression. The subgroup analysis showed that the superiority of BCG was mainly in those with concomitant CIS. In a multivariate analysis of association with recurrence/progression status, significant variables for outcome were type of drug, tumour size, multiplicity, status at second-look resection, and grade. A corresponding analysis was performed separately in the two treatment arms. Tumour size was the only significant variable for BCG-treated patients, while multiplicity, status at second-look resection, and grade were significant for patients treated with the combination. Conclusions: For prophylaxis of recurrence, BCG was more effective than the combination. There were no differences regarding progression and adverse events between the two treatments.

  • 14.
    Dyrskjot, Lars
    et al.
    Aarhus Univ Hosp, Dept Mol Med, Palle Juul Jensens Blvd, DK-8200 Aarhus N, Denmark.
    Reinert, Thomas
    Aarhus Univ Hosp, Dept Mol Med, Palle Juul Jensens Blvd, DK-8200 Aarhus N, Denmark.
    Algaba, Ferran
    Univ Autonoma Barcelona, Sect Pathol, Fundacio Puigvert, Barcelona, Spain.
    Christensen, Emil
    Aarhus Univ Hosp, Dept Mol Med, Palle Juul Jensens Blvd, DK-8200 Aarhus N, Denmark.
    Nieboer, Daan
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
    Hermann, Gregers G.
    Frederiksberg Univ Hosp, Dept Urol, Frederiksberg, Denmark.
    Mogensen, Karin
    Frederiksberg Univ Hosp, Dept Urol, Frederiksberg, Denmark.
    Beukers, Willemien
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands.
    Marquez, Mirari
    Spanish Natl Canc Res Ctr, Madrid, Spain.
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Hoyer, Soren
    Aarhus Univ Hosp, Dept Pathol, Aarhus, Denmark.
    Ulhoi, Benedicte P.
    Aarhus Univ Hosp, Dept Pathol, Aarhus, Denmark.
    Hartmann, Arndt
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, Erlangen, Germany.
    Stohr, Robert
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, Erlangen, Germany.
    Wach, Sven
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Urol, Erlangen, Germany.
    Nawroth, Roman
    Tech Univ Munich, Dept Urol, Klinikum Rechts Isar, Munich, Germany.
    Schwamborn, Kristina
    Tech Univ Munich, Inst Pathol, Klinikum Rechts Isar, Munich, Germany.
    Tulic, Cane
    Univ Belgrade, Clin Ctr Serbia, Clin Urol, Fac Med, Belgrade, Serbia.
    Simic, Tatjana
    Univ Belgrade, Inst Med & Clin Biochem, Fac Med, Belgrade, Serbia.
    Junker, Kerstin
    Saarland Univ, Dept Urol, Homburg, Germany.
    Harving, Niels
    Aalborg Univ Hosp, Dept Urol, Aalborg, Denmark.
    Petersen, Astrid C.
    Aalborg Univ Hosp, Dept Pathol, Aalborg, Denmark.
    Jensen, Jorgen B.
    Aarhus Univ Hosp, Dept Urol, Aarhus, Denmark.
    Keck, Bastian
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Urol, Erlangen, Germany.
    Grimm, Marc-Oliver
    Friedrich Schiller Univ Jena, Dept Urol, Jena, Germany.
    Horstmann, Marcus
    Friedrich Schiller Univ Jena, Dept Urol, Jena, Germany.
    Maurer, Tobias
    Tech Univ Munich, Dept Urol, Klinikum Rechts Isar, Munich, Germany.
    Steyerberg, Ewout W.
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands.
    Zwarthoff, Ellen C.
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands.
    Real, Francisco X.
    Spanish Natl Canc Res Ctr, Madrid, Spain;Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.
    Malats, Nuria
    Spanish Natl Canc Res Ctr, Madrid, Spain.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Orntoft, Torben F.
    Aarhus Univ Hosp, Dept Mol Med, Palle Juul Jensens Blvd, DK-8200 Aarhus N, Denmark.
    Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study2017Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, nr 3, s. 461-469Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed. Objective: To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study. Design, setting, and participants: We enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0-76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values. Outcome measurements and statistical analysis: We measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions. Results and limitations: The progression score was significantly (p < 0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guerin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p < 0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p < 0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R-2 = 0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/ 750 patients). Conclusions: The 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens. Patient summary: Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens.

  • 15.
    Elliott, Daisy
    et al.
    Univ Bristol, Sch Social & Community Med, Canynge Hall,39 Whatley Rd, Bristol BS8 2PS, Avon, England..
    Husbands, Samantha
    Univ Bristol, Sch Social & Community Med, Canynge Hall,39 Whatley Rd, Bristol BS8 2PS, Avon, England..
    Hamdy, Freddie C.
    Nuffield Dept Surg Sci, Oxford, England..
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Guys Hosp, Fac Life Sci & Med, Canc Epidemiol & Populat Hlth, London, England..
    Donovan, Jenny L.
    Univ Bristol, Sch Social & Community Med, Canynge Hall,39 Whatley Rd, Bristol BS8 2PS, Avon, England.;Univ Hosp Bristol NHS Trust, NIHR Collaborat Leadership Appl Hlth Res & Care W, Bristol, Avon, England..
    Understanding and Improving Recruitment to Randomised Controlled Trials: Qualitative Research Approaches2017Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, nr 5, s. 789-798Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Context: The importance of evidence from randomised trials is now widely recognised, although recruitment is often difficult. Qualitative research has shown promise in identifying the key barriers to recruitment, and interventions have been developed to reduce organisational difficulties and support clinicians undertaking recruitment. Objective: This article provides an introduction to qualitative research techniques and explains how this approach can be used to understand- and subsequently improve-recruitment and informed consent within a range of clinical trials. Evidence acquisition: A literature search was performed using Medline, Embase, and CINAHL. All studies with qualitative research methods that focused on the recruitment activity of clinicians were included in the review. Evidence synthesis: The majority of studies reported that organisational difficulties and lack of time for clinical staff were key barriers to recruitment. However, a synthesis of qualitative studies highlighted the intellectual and emotional challenges that arise when combining research with clinical roles, particularly in relation to equipoise and patient eligibility. To support recruiters to become more comfortable with the design and principles of randomised controlled trials, interventions have been developed, including the QuinteT Recruitment Intervention, which comprises in-depth investigation of recruitment obstacles in real time, followed by implementation of tailored strategies to address these challenges as the trial proceeds. Conclusions: Qualitative research can provide important insights into the complexities of recruitment to trials and inform the development of interventions, and provide support and training initiatives as required. Investigators should consider implementing such methods in trials expected to be challenging or recruiting below target. Patient summary: Qualitative research is a term used to describe a range of methods that can be implemented to understand participants' perspectives and behaviours. Data are gathered from interviews, focus groups, or observations. In this review, we demonstrate how this approach can be used to understand- and improve-recruitment to clinical trials. Taken together, our review suggests that healthcare professionals can find recruiting to trials challenging and require support with this process. (C) 2017 European Association of Urology. Published by Elsevier B.V.

  • 16. Gontero, Paolo
    et al.
    Bohle, Andreas
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    O'Donnell, Michael A.
    Oderda, Marco
    Sylvester, Richard
    Witjes, Fred
    The Role of Bacillus Calmette-Guerin in the Treatment of Non-Muscle-Invasive Bladder Cancer2010Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, nr 3, s. 410-429Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Context: Bacillus Calmette-Guerin (BCG) remains the most effective intravesical treatment for non-muscle-invasive bladder cancer (NMIBC), but the clinical development of BCG has been accompanied by controversy. Recent publications have called into question a number of aspects related to its use. Objective: To review the current clinical role of BCG in NMIBC, focusing on efficacy and tolerability as primary objectives and on strategies to predict response and decrease toxicity as secondary objectives. Evidence acquisition: We performed a systematic literature search of published articles in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases for the period from 1976 to November 2008. The following "free text'' combination was used in the first instance: "BCG and intravesical and bladder cancer.'' Further free text searches were performed by separately adding the following keywords to the combination "BCG and intravesical'': survival, progression, recurrence, maintenance, dosing, toxicity, tolerability, side effects, prognostic factors. Evidence synthesis: BCG is the most effective intravesical agent for preventing NMIBC recurrence, but its role in disease progression remains controversial. In intermediate-risk NMIBC, the superiority of BCG over chemotherapy is well established for disease recurrence but not for progression and needs to be balanced against higher toxicity. With regard to high-risk NMIBC, there is sufficient evidence to show that BCG is the most effective treatment of carcinoma in situ for ablation, disease-free interval, and progression, but the impact of BCG on the natural history of T1G3 tumors relies on a low level of evidence. Maintenance remains crucial for efficacy. The dose can be safely and effectively reduced to decrease its toxicity, which is slightly greater than chemotherapy. Conclusions: BCG should still be viewed as the most effective intravesical agent, but its role in the progression of papillary tumors needs to be clarified. BCG remains an alternative to intravesical chemotherapy in intermediate-risk NMIBC, and it is recommended as the standard of care for high-risk NMIBC.

  • 17. Gontero, Paolo
    et al.
    Sylvester, Richard
    Pisano, Francesca
    Joniau, Steven
    Eeckt, Kathy Vander
    Serretta, Vincenzo
    Larre, Stephane
    Di Stasi, Savino
    Van Rhijn, Bas
    Witjes, Alfred J.
    Grotenhuis, Anne J.
    Kiemeney, Lambertus A.
    Colombo, Renzo
    Briganti, Alberto
    Babjuk, Marek
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Oderda, Marco
    Irani, Jacques
    Malats, Nuria
    Baniel, Jack
    Mano, Roy
    Cai, Tommaso
    Cha, Eugene K.
    Ardelt, Peter
    Varkarakis, John
    Bartoletti, Riccardo
    Spahn, Martin
    Johansson, Robert
    Frea, Bruno
    Soukup, Viktor
    Xylinas, Evanguelos
    Dalbagni, Guido
    Karnes, R. Jeffrey
    Shariat, Shahrokh F.
    Palou, Joan
    Prognostic Factors and Risk Groups in T1G3 Non-Muscle-invasive Bladder Cancer Patients Initially Treated with Bacillus Calmette-Guerin: Results of a Retrospective Multicenter Study of 2451 Patients2015Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 67, nr 1, s. 74-82Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. Objective: To assess prognostic factors in patients who received bacillus Calmette Guerin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. Design, setting, and participants: Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. Outcome measurements and statistical analysis: Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). Results and limitations: With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age >= 70 yr, size >= 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients >= 70 yr with tumor size >= 3 cm and 13% otherwise. Conclusions: T1G3 patients >= 70 yr with tumors >= 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. Patient summary: Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guerin, there is a subgroup of T1G3 patients with age >= 70 yr, tumor size >= 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

  • 18.
    Guðmundsson, Eirikur
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Hellborg, Henrik
    Lundstam, Sven
    Erikson, Stina
    Ljungberg, Börje
    Metastatic Potential in Renal Cell Carcinomas <= 7 cm: Swedish Kidney Cancer Quality Register Data2011Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, nr 5, s. 975-982Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Renal cell carcinoma(RCC) represents 2-3% of all malignancies and accounts for approximately 90% of all kidney malignancies. An increasing proportion of RCCs are discovered incidentally, and the average tumor diameter at diagnosis has decreased over the last few decades. Small RCCs have often been regarded by many as relatively harmless.

    Objective: The objective was to evaluate the incidence of local T-category distribution and lymph node and distant metastases in relation to tumor size in RCCs <= 7 cm in a nationally based patient population.

    Design, setting, and participants: Data were extracted from the National Swedish Kidney Cancer Register containing 3489 RCCs diagnosed between 2005 and 2008. This is a population-based registry including 99% of all RCCs diagnosed nationwide. The study included 2033 patients having a tumor <= 7 cm in diameter.

    Measurements: The size of the tumors was compared with sex, age, cause of diagnosis, Fuhrman grade, RCC type, and TNM category.

    Results and limitations: Most RCCs were discovered incidentally and incidence correlated inversely to tumor size. There were 887 (43%) patients with category T1a tumors, 836 (40%) with category T1b, 174 (8%) with T3a, 131 (6%) with T3b/c, and 12 (1%) patients had invasion of adjacent organs (T4). A total of 309 (15%) patients had lymph node and/or distant metastases. Of the 177 1- to 2-cm RCCs, category T3 tumors were identified in three patients and lymph node and/or distant metastases were identified in 8 (5%). Only for tumors <= 1 cm was there neither advanced stage nor metastasis. The occurrence of locally advanced growth, lymph node and distant metastases, and high tumor grade correlated to tumor size. Patients with Fuhrman grade III or IV had a fourfold greater risk of metastases than grades I or II.

    Conclusions: Lymph node and distant metastases occur even in small RCCs. Risk of metastases increases with tumor size. The data clearly show that small RCCs also have a malignant potential and should be properly evaluated and adequately treated.

  • 19.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Obesity, Nutrition, and Prostate Cancer: Insights and Issues2013Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 63, nr 5, s. 821-822Artikel i tidskrift (Övrigt vetenskapligt)
  • 20.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Prostate cancer screening: the need for problem-solving that puts men's interests first2009Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 56, nr 1, s. 34-37Artikel i tidskrift (Refereegranskat)
  • 21. Iglesias-Gato, Diego
    et al.
    Wikström, Pernilla
    Tyanova, Stefka
    Lavallee, Charlotte
    Thysell, Elin
    Carlsson, Jessica
    Hägglöf, Christina
    Cox, Jürgen
    Andrén, Ove
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Departments of Surgery and Perioperative Sciences, Umea University, Umea, Sweden.
    Egevad, Lars
    Widmark, Anders
    Bjartell, Anders
    Collins, Colin C
    Bergh, Anders
    Geiger, Tamar
    Mann, Matthias
    Flores-Morales, Amilcar
    The Proteome of Primary Prostate Cancer.2016Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 69, nr 5, s. 942-52, artikel-id S0302-2838(15)01087-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Clinical management of the prostate needs improved prognostic tests and treatment strategies. Because proteins are the ultimate effectors of most cellular reactions, are targets for drug actions and constitute potential biomarkers; a quantitative systemic overview of the proteome changes occurring during prostate cancer (PCa) initiation and progression can result in clinically relevant discoveries.

    OBJECTIVES: To study cellular processes altered in PCa using system-wide quantitative analysis of changes in protein expression in clinical samples and to identify prognostic biomarkers for disease aggressiveness.

    DESIGN, SETTING, AND PARTICIPANTS: Mass spectrometry was used for genome-scale quantitative proteomic profiling of 28 prostate tumors (Gleason score 6-9) and neighboring nonmalignant tissue in eight cases, obtained from formalin-fixed paraffin-embedded prostatectomy samples. Two independent cohorts of PCa patients (summing 752 cases) managed by expectancy were used for immunohistochemical evaluation of proneuropeptide-Y (pro-NPY) as a prognostic biomarker.

    RESULTS AND LIMITATIONS: Over 9000 proteins were identified as expressed in the human prostate. Tumor tissue exhibited elevated expression of proteins involved in multiple anabolic processes including fatty acid and protein synthesis, ribosomal biogenesis and protein secretion but no overt evidence of increased proliferation was observed. Tumors also showed increased levels of mitochondrial proteins, which was associated with elevated oxidative phosphorylation capacity measured in situ. Molecular analysis indicated that some of the proteins overexpressed in tumors, such as carnitine palmitoyltransferase 2 (CPT2, fatty acid transporter), coatomer protein complex, subunit alpha (COPA, vesicle secretion), and mitogen- and stress-activated protein kinase 1 and 2 (MSK1/2, protein kinase) regulate the proliferation of PCa cells. Additionally, pro-NPY was found overexpressed in PCa (5-fold, p<0.05), but largely absent in other solid tumor types. Pro-NPY expression, alone or in combination with the ERG status of the tumor, was associated with an increased risk of PCa specific mortality, especially in patients with Gleason score ≤ 7 tumors.

    CONCLUSIONS: This study represents the first system-wide quantitative analysis of proteome changes associated to localized prostate cancer and as such constitutes a valuable resource for understanding the complex metabolic changes occurring in this disease. We also demonstrated that pro-NPY, a protein that showed differential expression between high and low risk tumors in our proteomic analysis, is also a PCa specific prognostic biomarker associated with increased risk for disease specific death in patients carrying low risk tumors.

    PATIENT SUMMARY: The identification of proteins whose expression change in prostate cancer provides novel mechanistic information related to the disease etiology. We hope that future studies will prove the value of this proteome dataset for development of novel therapies and biomarkers.

  • 22. Jansson, K Fredrik
    et al.
    Akre, Olof
    Garmo, Hans
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Adolfsson, Jan
    Stattin, Pär
    Bratt, Ola
    Concordance of tumor differentiation among brothers with prostate cancer2012Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 62, nr 4, s. 656-661Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Genetic factors seem to be of greater importance in prostate cancer than in other forms of cancer. Studies have suggested familial concordance in survival, but the extent to which that is due to tumor characteristics is not known.

    OBJECTIVE:

    We hypothesized that a brother of an index case with prostate cancer is at particularly increased risk of prostate cancer with the same tumor differentiation as the index case.

    DESIGN, SETTING AND PARTICIPANTS:

    We identified 21 930 brothers of index cases with prostate cancer in the Prostate Cancer Data Base Sweden and followed them up for incidence of prostate cancer.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

    The relative risk of Gleason score-specific prostate cancer in the cohort of brothers was estimated by using the standardized incidence ratio (SIR) stratified by Gleason score of the index case. We estimated 95% confidence intervals (CIs) assuming a Poisson distribution.

    RESULTS AND LIMITATIONS:

    Among brothers of index cases with Gleason score 8-10 cancer, the SIR was 2.53 (95% CI, 1.97-3.21) for a Gleason score 2-6 cancer and 4.00 (95% CI, 2.63-5.82) for a Gleason score 8-10 cancer. SIR for Gleason score 2-6 cancer among brothers decreased with time since the date of the index cases' diagnoses, whereas the risk of Gleason 8-10 cancer increased over time for brothers of index cases with Gleason 8-10 cancer (p for trend = 0.009).

    CONCLUSIONS:

    Brothers of men with high-grade prostate cancer are at particularly increased risk of high-grade prostate cancer. Likewise, there is a concordance of less malignant prostate cancers within families. These findings may have direct clinical relevance for counseling men with a family history of prostate cancer.

  • 23.
    Johansson, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Onelöv, Erik
    Johansson, Jan-Erik
    Steineck, Gunnar
    Time, symptom burden, androgen deprivation, and self-assessed quality of life after radical prostatectomy or watchful waiting: the Randomized Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) clinical trial2009Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 55, nr 2, s. 422-430Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Quality-of-life outcomes are important in the choice of treatment strategy for men with localized prostate cancer. OBJECTIVE: To evaluate how follow-up time, number of physical symptoms, and presence of androgen deprivation affected quality of life among men randomized to radical prostatectomy or watchful waiting. DESIGN, SETTING, AND PARTICIPANTS: The study group was composed of all 376 living men included in the Swedish part of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) between January 1, 1989, and February 29, 1996. Quality-of-life data were collected after a mean follow-up time of 4.1 yr. INTERVENTION: All patients were randomly assigned to radical prostatectomy or watchful waiting. Forty-five men were androgen deprived. MEASUREMENTS: Data of specific symptoms, symptom-induced stress, sense of well-being, and self-assessed quality of life were obtained by means of a questionnaire. Psychological symptoms were assessed using seven-point visual digital scales. RESULTS AND LIMITATIONS: In analyses stratified on the basis of the numbers of physical symptoms, anxiety and depressed mood were less common, and sense of well-being and self-assessed quality of life were better throughout in the radical prostatectomy group than in the watchful waiting group. As the number of physical symptoms increased, all psychological variables became worse and more prominent in the watchful waiting group. After a follow-up time of 6-8 yr, a significant decrease in quality of life (p=0.03) was seen in the watchful waiting group. Twenty-four percent of androgen-deprived patients assigned to watchful waiting reported high self-assessed quality of life compared with 60% in the radical prostatectomy group. Eighty-eight percent of patients had clinically detected tumors. CONCLUSIONS: Androgen deprivation negatively affected self-assessed quality of life in men assigned to watchful waiting. The number of physical symptoms was associated with the level of quality of life. Quality of life was lower with longer follow-up time in both groups and was statistically significant in the watchful waiting group (p=0.03).

  • 24.
    Kellokumpu-Lehtinen, Pirkko-Liisa
    et al.
    Tampere Univ Hosp, POB 2000, Tampere 33521, Finland.
    Hjälm-Eriksson, Marie
    Capio St Gorans Hosp, Dept Surg, Stockholm, Sweden;Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden.
    Thellenberg-Karlsson, Camilla
    Umea Univ Hosp, Dept Radiat Sci, Oncol, Umea, Sweden.
    Åström, Lennart
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Franzen, Lars
    Sundsvall Univ Hosp, Sundsvall, Sweden.
    Fransson, Ann-Sofie
    Gavle Cent Hosp, Gavle, Sweden.
    Leskinen, Markku J.
    Seinajoki Cent Hosp, Seinajoki, Finland.
    Zeke, Mihalj
    Vaxjo Cent Hosp, Vaxjo, Sweden.
    Huttunen, Teppo
    4Pharma, Turku, Finland.
    Ginman, Claes
    Karlstad Cent Hosp, Karlstad, Sweden.
    Docetaxel Versus Surveillance After Radical Radiotherapy for Intermediate- or High-risk Prostate Cancer-Results from the Prospective, Randomised, Open-label Phase III SPCG-13 Trial2019Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, nr 6, s. 823-830Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Docetaxel combined with androgen deprivation therapy (ADT) has improved patient survival for advanced prostate cancer (PCa). Objective: This randomised trial aimed to evaluate whether six courses of docetaxel improved biochemical disease-free survival (BDFS) after radical radiotherapy (RT) for intermediate- or high-risk PCa patients. Design, setting, and participants: A total of 376 patients were randomised in this multinational phase III study, and received either six cycles of adjuvant docetaxel 75 mg/m(2) every 3 wk without continuous prednisone (arm A, n =188) or surveillance (arm B, n = 188) after RT (NTC006653848). Neoadjuvant/adjuvant ADT was mandatory for all the patients. The primary endpoint was rising prostate-specific antigen (PSA) >= 2 ng/ml above the nadir PSA value. Intermediate- or high-risk PCa was defined as T2 with a Gleason score (GS) of 4 +3, PSA > 10; T2, GS 8-10, <= 70 ng/ml; or any T3. The patients were followed for 5 yr by assessing PSA levels every 3 mo for 2 yr and every 6 mo thereafter. Outcome measurements and statistical analysis: The study power was 89% to detect a difference in BDFS between groups, and the sample size calculation accounted for the T2/T3 distribution, where a 12%/15% difference in BDFS was assumed for the T2/T3 patients. Results and limitations: All six cycles were completed in 147 (78%) of the patients in arm A. The median age was 67 yr in both treatment groups, 75% had T3 disease, and 47% had GS 8-10. The median follow-up was 59 mo (range 1-111 mo). The primary endpoint was observed for 58 patients in arm A (docetaxel) and for 57 patients in arm B (surveillance). The Kaplan-Meier analysis showed no difference in the BDFS curves (p = 0.6) between the treatment groups. The 5-yr estimated biochemical progression rates were 31% for arm A and 28% for arm B. Febrile neutropenia occurred in 16% of the docetaxel patients.No deaths were related to the docetaxel treatment. There were 43 deaths during the trial, including 20 in arm A and 23 in arm B, of which nine and seven, respectively, were due to PCa. The hazard ratio from Cox multivariate analysis for PSA progression of arm A (docetaxel) versus arm B (surveillance) was 1.14 (95% confidence interval 0.79-1.64, p = 0.5). Conclusions: Adjuvant docetaxel without prednisone did not improve BDFS after radical RT with ADT for intermediate- or high-risk PCa. Patient summary: We compared six cycles of adjuvant docetaxel given after radical external radiotherapy plus androgen deprivation therapy to surveillance in intermediate- and high-risk localised prostate cancer. We found no overall benefit in this setting. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 25.
    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 Review2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 3, s. 261-280Artikel, forskningsöversikt (Refereegranskat)
    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. 

  • 26.
    Krantz, David
    et al.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Hartana, Ciputra Adijaya
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Winerdal, Malin E.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Johansson, Markus
    Sundsvall Hosp, Dept Urol, Sundsvall, Sweden;Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Dept Urol, Vasteras, Sweden.
    Jakubczyk, Tomasz
    Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden.
    Huge, Ylva
    Linkoping Univ, Dept Clin & Expt Med, Div Urol, Linkoping, Sweden.
    Aljabery, Firas
    Linkoping Univ, Dept Clin & Expt Med, Div Urol, Linkoping, Sweden.
    Palmqvist, Karin
    Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden;Ostersund Cty Hosp, Dept Surg, Urol Sect, Ostersund, Sweden.
    Zirakzadeh, A. Ali
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden;Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden.
    Holmstrom, Benny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Riklund, Katrine
    Umea Univ, Dept Radiat Sci, Diagnost Radiol, Umea, Sweden.
    Sherif, Amir
    Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden;Linkoping Univ, Dept Clin & Expt Med, Div Urol, Linkoping, Sweden.
    Winqvist, Ola
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Neoadjuvant Chemotherapy Reinforces Antitumour T cell Response in Urothelial Urinary Bladder Cancer2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 6, s. 688-692Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Evidence indicates that neoadjuvant chemotherapy (NAC) may promote antitumour immune responses by activating T cells. The tumour-draining sentinel node (SN) is a key site to study tumour-specific T cell activation, being the primary immunological barrier against the tumour. In this prospective study, we set out to elucidate the effects of NAC on T cell subsets in the SNs of patients with muscle-invasive urothelial bladder cancer. We found that CD8(+) effector T (Teff) cell exhaustion was reduced after NAC treatment, while cytotoxicity was increased. Additionally, in complete responders (CR patients), these cells were functionally committed effectors, as displayed by epigenetic analysis. In CD4(+) Teffs, NAC treatment was associated with increased clonal expansion of tumour-specific SN-derived cells, as demonstrated by a specific cell reactivity assay. In contrast, we observed an attenuating effect of NAC on regulatory T cells (Tregs) with a dose-dependent decrease in Treg frequency and reduced effector molecule expression in the remaining Tregs. In addition, multicolour flow cytometry analysis revealed that CR patients had higher Teff to activated Treg ratio, promoting antitumoural T cell activation. These results suggest that NAC reinforces the antitumour immune response by activating the effector arm of the T cell compartment and diminishing the influence of suppressive Tregs. Patient summary: In this report, we analysed the effect of chemotherapy on immune cell subsets of 40 patients with advanced bladder cancer. We found that chemotherapy has a positive effect on immune effector T cells, whereas an opposite, diminishing effect was observed for immune-suppressive regulatory T cells. We conclude that chemotherapy reinforces the antitumour immune response in bladder cancer patients.

  • 27.
    Ladjevardi, Sam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Sandblom, Gabriel
    Berglund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Varenhorst, Eberhard
    Tumour Grade, Treatment, and Relative Survival in a Population-based Cohort of Men with Potentially Curable Prostate Cancer2010Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, nr 4, s. 631-638Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There is insufficient information regarding the benefit of treatment with curative intent for men with localised poorly differentiated prostate cancer (PCa). Objective: To evaluate relative survival in men with potentially curable PCa in relation to Gleason score (GS) and treatment as practiced in the community at large. Design, setting, and participants: A population-based study including all men with localised PCa registered in Sweden's National Prostate Cancer Register. Interventions: Hormonal therapy, watchful waiting, and treatment with curative intent. Measurements: The ratio of observed deaths to expected deaths, determined from survival in the general male population of the same age, was assessed using Poisson regression analysis, with GS and treatment as covariates. Interaction between GS and treatment was tested in a multivariate Cox proportional hazard analysis. Results and limitations: A total of 31 903 men with potentially curable tumour (T1-T3, N0/NX, M0/MX, age < 75 yr, and prostate-specific antigen [PSA] < 20 ng/ml) were identified. GS was recorded for 28 454 of these men. Some 19 606 men (60.8%) were treated with curative intent, and 12 645 men (39.2%) were given either hormonal treatment or expectant management. The ratios between observed and expected survival gradually increased for men with GS 10, with GS to 3.3 for men treated conservatively and to 1.4 for men treated with curative intent. There was a significant interaction between GS and treatment, with a relatively greater benefit from treatment with curative intent for men with high-grade tumours. The results have to be interpreted with some caution, as there was no randomisation between the treatment groups. Conclusions: Survival for men with well-differentiated tumours is close to that of the general population, regardless of treatment, but the outcome is dismal for men with poorly differentiated tumours, whichever treatment is applied. Nevertheless, men with poorly differentiated tumours benefit more from curative treatment than do men with well-differentiated tumours.

  • 28.
    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 Survival2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 6, s. 710-719Artikel i tidskrift (Refereegranskat)
    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.

  • 29. Loeb, Stacy
    et al.
    Folkvaljon, Yasin
    Makarov, Danil V.
    Bratt, Ola
    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.
    Five-year Nationwide Follow-up Study of Active Surveillance for Prostate Cancer2015Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 67, nr 2, s. 233-238Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Active surveillance (AS) is an important yet underutilized strategy to reduce prostate cancer (PCa) overtreatment. Objective: To examine the 5-yr outcomes of AS in a population-based setting. Design, setting, and participants: From the National Prostate Cancer Register of Sweden, we identified 11 726 men <= 70 yr diagnosed with very low-risk to intermediate-risk PCa from 2003 to 2007 who completed 5 yr of follow-up. Of these men, 1729 (15%) chose AS for the primary management strategy. Outcome measurements and statistical analysis: We calculated the probability of discontinuation of AS over time, and Cox proportional hazards models were used to determine factors associated with discontinuation. Reasons for discontinuation were assessed by data extraction from medical charts. Results and limitations: By 5 yr, 64% of the men remained on AS. Predictors of discontinuation were younger age, fewer comorbidities, more education, higher prostate-specific antigen (PSA), and clinical stage T2 disease; marital status did not predict discontinuation. In a subset with data on the reason for discontinuation (86%), 20% of men discontinued because of patient preference, 52% because of PSA progression, 24% because of biopsy progression, and 3% for other reasons. Conclusions: In a population-based setting, the majority of men remained on AS at 5 yr. However, one-fifth of the men who discontinued AS did so for nonbiologic reasons. Thus, there is a need for support and counseling for men to continue AS in the absence of signs of progression to improve adherence to AS and decrease overtreatment. Patient summary: Active surveillance (AS) is an important option to delay or avoid treatment for men with favorable prostate cancer features. This study shows that at 5 yr, 64% of men across an entire population remained on AS. We concluded that AS is a durable option and that counseling may be useful to promote adherence for men without progression. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 30.
    Loeb, Stacy
    et al.
    NYU, Dept Urol & Populat Hlth, New York, NY 10003 USA.;Manhattan Vet Affairs Med Ctr, New York, NY USA..
    Folkvaljon, Yasin
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Robinson, David
    Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umea, Sweden..
    Lissbrant, Ingela Franck
    Sahlgrens Univ Hosp, Dept Oncol & Radiat Phys, Gothenburg, Sweden..
    Egevad, Lars
    Karolinska Univ Hosp, Dept Pathol, Stockholm, 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, S-90185 Umea, Sweden.
    Evaluation of the 2015 Gleason Grade Groups in a Nationwide Population-based Cohort2016Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 69, nr 6, s. 1135-1141Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: New five-tiered Gleason grade groups (GGGs) were recently proposed, in which Gleason 6 is GGG 1, Gleason 3 + 4 is GGG 2, Gleason 4 + 3 is GGG 3, Gleason 8 is GGG 4, and Gleason 9-10 is GGG 5. Objective: To examine the performance of the new GGGs in men with prostate cancer from a nationwide population-based cohort. Design, setting, and participants: From the National Prostate Cancer Register of Sweden, we identified 5880 men diagnosed with prostate cancer from 2005 to 2007, including 4325 who had radical prostatectomy and 1555 treated with radiation therapy. Outcome measurements and statistical analysis: Kaplan-Meier survival analysis, Cox proportional hazards models, and concordance indices were used to examine the relationship between the GGGs and biochemical recurrence after radical prostatectomy and radiation therapy. Results and limitations: Among men treated with surgery, the 4-yr biochemical recurrence-free survival rates were 89%, 82%, 74%, 77%, and 49% for GGG 1-5 on biopsy, and 92%, 85%, 73%, 63%, and 51% based on prostatectomy GGG, respectively. For men treated by radiation therapy, men with biopsy GGG of 1-5 had 4-yr biochemical recurrence-free survival rates of 95%, 91%, 85%, 78%, and 70%. Adjusting for preoperative serum prostate-specific antigen and clinical stage, biopsy GGGs were significant independent predictors of biochemical recurrence after radical prostatectomy and radiation therapy. The new 5-tier system resulted in virtually no change in predictive accuracy compared with the current 3- and 4-tier classifications. Limitations include a median follow-up of 4.6 yr, precluding the ability to examine long-term oncologic outcomes. Conclusions: The newly proposed GGGs offer a simplified, user-friendly nomenclature to aid in patient counseling, with similar predictive accuracy in a population-based setting to previous classifications. Patient summary: The new Gleason grade groups, ranging from 1-5, provide a simplified, user-friendly classification system to predict the risk of recurrence after prostatectomy and radiation therapy.

  • 31.
    Loeb, Stacy
    et al.
    NYU, Dept Urol Populat Hlth, 550 1st Ave, New York, NY 10016 USA.;NYU, Laura & Isaac Perlmutter Canc Ctr, 550 1st Ave, New York, NY 10016 USA..
    Folkvaljon, Yasin
    Univ Uppsala Hosp, Registers & Care Programs, Uppsala, Sweden..
    Robinson, David
    Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Schlomm, Thorsten
    Univ Med Ctr Hamburg Eppendorf, Martini Clin Prostate Canc Ctr, Hamburg, Germany..
    Garmo, Hans
    Kings Coll London, Div Canc Studies, Canc Epidemiol Unit, 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.;Univ Uppsala Hosp, Dept Urol, Uppsala, Sweden..
    Phosphodiesterase Type 5 Inhibitor Use and Disease Recurrence After Prostate Cancer Treatment2016Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, nr 5, s. 824-828Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Phosphodiesterase type 5 inhibitor (PDE5i) use is common for management of erectile dysfunction. Single-institution studies have reported conflicting data on the relationship between PDE5i use and biochemical recurrence of prostate cancer (BCR) after radical prostatectomy. Objective: To evaluate the association between PDE5i use and BCR after radical prostatectomy and radiation therapy in a nationwide population-based cohort. Design, setting, and participants: This was a nested case-control study using the National Prostate Cancer Register of Sweden linked to the Prescribed Drug Register. Among men with localized prostate cancer who underwent primary radical prostatectomy or radiation therapy during 2006-2007 with 5 yr of follow-up, 293 had BCR after treatment (cases). For each case we identified 20 BCR-free controls (n = 5767) using incidence density sampling. Outcome measurements and statistical analysis: Multivariable conditional logistic regression was used to examine the association between PDE5i use and BCR risk. Separate multivariable models including clinical variables for men undergoing prostatectomy or radiotherapy and including surgical pathology after prostatectomy were also analyzed. Results and limitations: PDE5i use was not associated with BCR after radical prostatectomy (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.59-1.03) or radiation therapy (OR 0.98, 95% CI 0.49-1.97) after adjusting for marital status, education, income, prostate-specific antigen, clinical stage, Gleason score, and proportion of positive biopsies. Results were similar after additional adjustment for surgical pathology (OR 0.86, 95% CI 0.64-1.16). Men whose cumulative number of PDE5i pills was above the median had a slightly lower BCR risk after prostatectomy in the clinical model, and no difference in BCR risk after adjustment for pathologic tumor features. Conclusions: Our results from a population-based cohort suggest that BCR risk is not higher among men using PDE5i after prostate cancer treatment. Patient summary: Erectile dysfunction medications are not associated with a higher risk of disease recurrence after prostate cancer treatment.

  • 32. Loeb, Stacy
    et al.
    Schlomm, Thorsten
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Associations Do Not Equal Causation: Clinical Relevance of Statistical Associations of Phosphodiesterase Type 5 Inhibitors with Prostate Cancer Progression and Melanoma.2015Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 68, nr 5, s. 754-755, artikel-id S0302-2838(15)00668-5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A recent study reported a detrimental effect of phosphodiesterase type 5 inhibitors(PDE5-Is) on biochemical recurrence (BCR) after radical prostatectomy (RP) for prostatecancer (PCa). We tested the association between PDE5-I use, PDE5-I therapy scheme,number of PDE5-I pills taken, and BCR in 2579 patients treated with bilateral nerve-sparing RP for PCa between 2004 and 2013 at a single center. Patients were categorizedaccording to PDE5-I use within 2 yr after surgery ason demand, rehabilitation schedule(daily PDE5-I use for at least 3 mo), andno PDE5-I use. Multivariable (MVA) Coxregression models tested the association between PDE5-I and BCR. The same analyseswere repeated using the number of PDE5-I pills taken by each patient. Overall,674 patients (26.1%) received PDE5-Is. At MVA analysis, PDE5-I use, type of administra-tion schedule, and number of PDE5-I pills were not significantly associated with higherrisk of BCR (allp0.2) after accounting for multiple confounders including time from RPto PDE5-I use. While awaiting further studies, patients should not be denied PDE5-Itreatment after RP.Patient summary:Among patients treated with radical prostatectomy, phosphodies-terase type 5 inhibitor use was not associated with an increased risk of biochemicalrecurrence, regardless of the therapeutic regimen used.

  • 33.
    Loeb, Stacy
    et al.
    NYU, Dept Urol Populat Hlth, New York, NY 10003 USA.;NYU, Laura & Isaac Perlmutter Canc Ctr, New York, NY 10003 USA..
    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..
    Further Evidence against a Causal Association between Erectile Dysfunction Drugs and Melanoma2016Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, nr 5, s. 816-817Artikel i tidskrift (Övrigt vetenskapligt)
  • 34. Machiela, Mitchell J
    et al.
    Hofmann, Jonathan N
    Carreras-Torres, Robert
    Brown, Kevin M
    Johansson, Mattias
    Wang, Zhaoming
    Foll, Matthieu
    Li, Peng
    Rothman, Nathaniel
    Savage, Sharon A
    Gaborieau, Valerie
    McKay, James D
    Ye, Yuanqing
    Henrion, Marc
    Bruinsma, Fiona
    Jordan, Susan
    Severi, Gianluca
    Hveem, Kristian
    Vatten, Lars J
    Fletcher, Tony
    Koppova, Kvetoslava
    Larsson, Susanna C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Banks, Rosamonde E
    Selby, Peter J
    Easton, Douglas F
    Pharoah, Paul
    Andreotti, Gabriella
    Freeman, Laura E Beane
    Koutros, Stella
    Albanes, Demetrius
    Mannisto, Satu
    Weinstein, Stephanie
    Clark, Peter E
    Edwards, Todd E
    Lipworth, Loren
    Gapstur, Susan M
    Stevens, Victoria L
    Carol, Hallie
    Freedman, Matthew L
    Pomerantz, Mark M
    Cho, Eunyoung
    Kraft, Peter
    Preston, Mark A
    Wilson, Kathryn M
    Gaziano, J Michael
    Sesso, Howard S
    Black, Amanda
    Freedman, Neal D
    Huang, Wen-Yi
    Anema, John G
    Kahnoski, Richard J
    Lane, Brian R
    Noyes, Sabrina L
    Petillo, David
    Colli, Leandro M
    Sampson, Joshua N
    Besse, Celine
    Blanche, Helene
    Boland, Anne
    Burdette, Laurie
    Prokhortchouk, Egor
    Skryabin, Konstantin G
    Yeager, Meredith
    Mijuskovic, Mirjana
    Ognjanovic, Miodrag
    Foretova, Lenka
    Holcatova, Ivana
    Janout, Vladimir
    Mates, Dana
    Mukeriya, Anush
    Rascu, Stefan
    Zaridze, David
    Bencko, Vladimir
    Cybulski, Cezary
    Fabianova, Eleonora
    Jinga, Viorel
    Lissowska, Jolanta
    Lubinski, Jan
    Navratilova, Marie
    Rudnai, Peter
    Szeszenia-Dabrowska, Neonila
    Benhamou, Simone
    Cancel-Tassin, Geraldine
    Cussenot, Olivier
    Bueno-de-Mesquita, H B As
    Canzian, Federico
    Duell, Eric J
    Ljungberg, Börje
    Sitaram, Raviprakash T
    Peters, Ulrike
    White, Emily
    Anderson, Garnet L
    Johnson, Lisa
    Luo, Juhua
    Buring, Julie
    Lee, I-Min
    Chow, Wong-Ho
    Moore, Lee E
    Wood, Christopher
    Eisen, Timothy
    Larkin, James
    Choueiri, Toni K
    Lathrop, G Mark
    Teh, Bin Tean
    Deleuze, Jean-Francois
    Wu, Xifeng
    Houlston, Richard S
    Brennan, Paul
    Chanock, Stephen J
    Scelo, Ghislaine
    Purdue, Mark P
    Corrigendum re "Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma": [Eur Urol 2017;72:747-542018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 3, s. e85-e86, artikel-id S0302-2838(18)30366-XArtikel i tidskrift (Refereegranskat)
  • 35. Machiela, Mitchell J
    et al.
    Hofmann, Jonathan N
    Carreras-Torres, Robert
    Brown, Kevin M
    Johansson, Mattias
    Wang, Zhaoming
    Foll, Matthieu
    Li, Peng
    Rothman, Nathaniel
    Savage, Sharon A
    Gaborieau, Valerie
    McKay, James D
    Ye, Yuanqing
    Henrion, Marc
    Bruinsma, Fiona
    Jordan, Susan
    Severi, Gianluca
    Hveem, Kristian
    Vatten, Lars J
    Fletcher, Tony
    Koppova, Kvetoslava
    Larsson, Susanna C
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wolk, Alicja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Banks, Rosamonde E
    Selby, Peter J
    Easton, Douglas F
    Pharoah, Paul
    Andreotti, Gabriella
    Freeman, Laura E Beane
    Koutros, Stella
    Albanes, Demetrius
    Mannisto, Satu
    Weinstein, Stephanie
    Clark, Peter E
    Edwards, Todd E
    Lipworth, Loren
    Gapstur, Susan M
    Stevens, Victoria L
    Carol, Hallie
    Freedman, Matthew L
    Pomerantz, Mark M
    Cho, Eunyoung
    Kraft, Peter
    Preston, Mark A
    Wilson, Kathryn M
    Gaziano, J Michael
    Sesso, Howard S
    Black, Amanda
    Freedman, Neal D
    Huang, Wen-Yi
    Anema, John G
    Kahnoski, Richard J
    Lane, Brian R
    Noyes, Sabrina L
    Petillo, David
    Colli, Leandro M
    Sampson, Joshua N
    Besse, Celine
    Blanche, Helene
    Boland, Anne
    Burdette, Laurie
    Prokhortchouk, Egor
    Skryabin, Konstantin G
    Yeager, Meredith
    Mijuskovic, Mirjana
    Ognjanovic, Miodrag
    Foretova, Lenka
    Holcatova, Ivana
    Janout, Vladimir
    Mates, Dana
    Mukeriya, Anush
    Rascu, Stefan
    Zaridze, David
    Bencko, Vladimir
    Cybulski, Cezary
    Fabianova, Eleonora
    Jinga, Viorel
    Lissowska, Jolanta
    Lubinski, Jan
    Navratilova, Marie
    Rudnai, Peter
    Szeszenia-Dabrowska, Neonila
    Benhamou, Simone
    Cancel-Tassin, Geraldine
    Cussenot, Olivier
    Bueno-de-Mesquita, H Bas
    Canzian, Federico
    Duell, Eric J
    Ljungberg, Börje
    Sitaram, Raviprakash T
    Peters, Ulrike
    White, Emily
    Anderson, Garnet L
    Johnson, Lisa
    Luo, Juhua
    Buring, Julie
    Lee, I-Min
    Chow, Wong-Ho
    Moore, Lee E
    Wood, Christopher
    Eisen, Timothy
    Larkin, James
    Choueiri, Toni K
    Lathrop, G Mark
    Teh, Bin Tean
    Deleuze, Jean-Francois
    Wu, Xifeng
    Houlston, Richard S
    Brennan, Paul
    Chanock, Stephen J
    Scelo, Ghislaine
    Purdue, Mark P
    Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma.2017Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, nr 5, s. 747-754, artikel-id S0302-2838(17)30639-5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings.

    OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.

    DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis.

    RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13).

    CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk.

    PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.

  • 36.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Re: Randomized Phase III Trial on Gemcitabine Versus Mytomicin in Recurrent Superficial Bladder Cancer: Evaluation of Efficacy and Tolerance2010Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 58, nr 1, s. 178-Artikel i tidskrift (Refereegranskat)
  • 37.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    "To Improve Is To Change; To Be Perfect Is To Change Often"2014Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 65, nr 2, s. 358-359Artikel i tidskrift (Övrigt vetenskapligt)
  • 38.
    Malmström, Per-Uno
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Sylvester, Richard J.
    Crawford, David E.
    Friedrich, Martin
    Krege, Susanne
    Rintala, Erkki
    Solsona, Eduardo
    Di Stasi, Savino M.
    Witjes, J. Alfred
    An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guérin for non-muscle-invasive bladder cancer2009Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 56, nr 2, s. 247-56Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Patients with non-muscle-invasive bladder cancer with an intermediate or high risk need adjuvant intravesical therapy after surgery. Based largely on meta-analyses of previously published results, guidelines recommend using either bacillus Calmette-Guérin (BCG) or mitomycin C (MMC) in these patients. Individual patient data (IPD) meta-analyses, however, are the gold standard. OBJECTIVE: To compare the efficacy of BCG and MMC based on an IPD meta-analysis of randomised trials. DESIGN, SETTING, AND PARTICIPANTS: Trials were searched through Medline and review articles. The relevant trial investigators were contacted to provide IPD. MEASUREMENTS: The drugs were compared with respect to time to recurrence, progression, and overall and cancer-specific death. RESULTS AND LIMITATIONS: Nine trials that included 2820 patients were identified, and IPD were obtained from all of them. Patient characteristics were 71% primary, 54% Ta, 43% T1, 25% G1, 58% G2, and 16% G3, and 7% had prior intravesical chemotherapy. Based on a median follow-up of 4.4 yr, 43% recurred. Overall, there was no difference in the time to first recurrence (p=0.09) between BCG and MMC. In the trials with BCG maintenance, a 32% reduction in risk of recurrence on BCG compared to MMC was found (p<0.0001), while there was a 28% risk increase (p=0.006) for BCG in the trials without maintenance. BCG with maintenance was more effective than MMC in both patients previously treated and those not previously treated with chemotherapy. In the subset of 1880 patients for whom data on progression, survival, and cause of death were available, 12% progressed and 24% died, and, of those, 30% of the deaths were due to bladder cancer. No statistically significant differences were found for these long-term end points. CONCLUSIONS: For prophylaxis of recurrence, maintenance BCG is required to demonstrate superiority to MMC. Prior intravesical chemotherapy was not a confounder. There were no statistically significant differences regarding progression, overall survival, and cancer-specific survival between the two treatments.

  • 39.
    Malmström, Per-Uno
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Trock, Bruce J.
    Johns Hopkins Med Inst, Div Epidemiol, Baltimore, MD 21205 USA.
    Re: Richard J. Sylvester, Willem Oosterlinck, Sten Holmang, et al. Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder: Which Patients Benefit from the Instillation? Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2015.05.0502015Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 69, nr 1, s. E10-E11Artikel i tidskrift (Refereegranskat)
  • 40. Martin, Neil E
    et al.
    Massey, Laura
    Stowell, Caleb
    Bangma, Chris
    Briganti, Alberto
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Blute, Michael
    Catto, James
    Chen, Ronald C
    D'Amico, Anthony V
    Feick, Günter
    Fitzpatrick, John M
    Frank, Steven J
    Froehner, Michael
    Frydenberg, Mark
    Glaser, Adam
    Graefen, Markus
    Hamstra, Daniel
    Kibel, Adam
    Mendenhall, Nancy
    Moretti, Kim
    Ramon, Jacob
    Roos, Ian
    Sandler, Howard
    Sullivan, Francis J
    Swanson, David
    Tewari, Ashutosh
    Vickers, Andrew
    Wiegel, Thomas
    Huland, Hartwig
    Defining a Standard Set of Patient-centered Outcomes for Men with Localized Prostate Cancer2015Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 67, nr 3, s. 460-467Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment.

    OBJECTIVE: To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value.

    DESIGN, SETTING, AND PARTICIPANTS: We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set.

    RESULTS AND LIMITATIONS: We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons.

    CONCLUSIONS: We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care.

    PATIENT SUMMARY: Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer.

  • 41. Oosterlinck, Willem
    et al.
    Kirkali, Ziya
    Sylvester, Richard
    da Silva, Fernando Calais
    Busch, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Algaba, Ferran
    Collette, Sandra
    Bono, Aldo
    Sequential Intravesical Chemoimmunotherapy with Mitomycin C and Bacillus Calmette-Guerin and with Bacillus Calmette-Guerin Alone in Patients with Carcinoma in Situ of the Urinary Bladder: Results of an EORTC Genito-Urinary Group Randomized Phase 2 Trial (30993)2011Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 59, nr 3, s. 438-446Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Bacillus Calmette-Guerin (BCG) is the intravesical treatment of choice for carcinoma in situ (CIS). Objective: Our aim was to assess if sequential mitomycin C (MMC) plus BCG after transurethral resection (TUR) is worthy of further study in non-muscle-invasive bladder cancer patients with CIS. Design, setting, and participants: In a noncomparative phase 2 study, 96 patients with primary/secondary/concurrent CIS of the urinary bladder were randomized to sequential MMC plus BCG or to BCG alone after TUR. Intervention: Patients received six weekly instillations of MMC followed by six weekly instillations of BCG or six weekly instillations of BCG, 3 wk rest, and three further weekly instillations of BCG. Complete responders received three weekly maintenance instillations at 6, 12, 18, 24, 30, and 36 mo in accordance with the initial randomization. Measurements: End points were complete response (CR) rate at the first control cystoscopy 16-18 wk after start of treatment, disease-free interval, overall survival, and side effects. Results and limitations: Ninety-six patients were randomized, 48 to each treatment group. Ten patients were ineligible, and three did not start treatment. In all random-ized patients, CR rates on MMC plus BCG and BCG alone were 70.8% and 66.7%, respectively. In 83 eligible patients who started treatment, CR rates were 75.6% and 73.8%, respectively. Based on a median follow-up of 4.7 yr, 25 patients (52.1%) on MMC plus BCG and 22 patients (45.8%) on BCG alone were disease free. Twelve patients stopped treatment due to toxicity: three during induction (two MMC plus BCG, one BCG) and nine during maintenance (three MMC plus BCG, six BCG). Conclusions: In the treatment of patients with CIS, sequential chemoimmunotherapy with MMC plus BCG had acceptable toxicity. CR and disease-free rates were similar to those on BCG alone and to previous publications on sequential chemoimmunotherapy.

  • 42.
    Plym, Anna
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, POB 281, S-17177 Stockholm, Sweden..
    Chiesa, Flaminia
    Karolinska Inst, Dept Med Epidemiol & Biostat, POB 281, S-17177 Stockholm, Sweden..
    Voss, Margaretha
    Swedish Social Insurance Agcy, Dept Anal & Forecast, Stockholm, Sweden.;Karolinska Inst, Dept Clin Neurosci, Div Insurance Med, Stockholm, Sweden..
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Sch Med, Div Canc Studies, Canc Epidemiol Grp, London WC2R 2LS, England..
    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. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Lambe, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Karolinska Inst, Dept Med Epidemiol & Biostat, POB 281, S-17177 Stockholm, Sweden..
    Work Disability After Robot-assisted or Open Radical Prostatectomy: A Nationwide, Population-based Study2016Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, nr 1, s. 64-71Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Robot-assisted radical prostatectomy (RARP) has been associated with reduced bleeding and shorter hospital stays than open retropubic radical prostatectomy (RRP), but it is unclear whether these differences translate into shorter absence from work. Objective: To investigate short-and long-term rates of work disability following RARP and RRP. Design, setting, and participants: We conducted a nationwide population-based cohort study of 2571 men of working age treated with RARP or RRP between 2007 and 2009 identified in the National Prostate Cancer Register of Sweden. Information about physician-certified sick leave and disability pension was retrieved from the Swedish Social Insurance Agency through 2012. Outcome measurements and statistical analysis: We used Cox regression to calculate time to return to work (RTW, or duration of sick leave) after surgery and used generalised estimating equations to analyse days lost from work (because of sick leave and disability pension) after RTW. Results and limitations: Men treated with RARP returned to work after a median of 35 d, whereas the corresponding time for RRP was 48 d (p < 0.001). The difference was seen early; within the first month, men treated with RARP returned to work nearly four times faster than men treated with RRP (adjusted relative RTW rate 3.76; 95% confidence interval [CI], 3.04-4.66). During a median of 3.6 yr after return to work, men treated with RARP lost fewer days from work per person-year than men treated with RRP-12 d versus 15 d-but the association was not statistically significant (p = 0.10). The adjusted rate ratio was 1.08 (95% CI, 0.82-1.42). One limitation is the nonrandomised design of this study. Conclusions: RARP was associated with a faster RTW compared with RRP, but the surgical method did not influence long-term rates of work disability in terms of days lost from work after RTW. Patient summary: We compared disease-related absence from work between two surgical methods for the removal of the prostate. Robot-assisted surgery was associated with a faster return to work compared with open surgery but did not influence absence from work in a long-term perspective.

  • 43.
    Plym, Anna
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, POB 281, SE-17177 Stockholm, Sweden..
    Voss, Margaretha
    Swedish Social Insurance Agcy, Dept Anal & Forecast, Stockholm, Sweden.;Karolinska Inst, Dept Clin Neurosci, Div Insurance Med, 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..
    Lambe, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Karolinska Inst, Dept Med Epidemiol & Biostat, POB 281, SE-17177 Stockholm, Sweden..
    Reply from Authors re: Matthew T. Gettman. Assessing Work Disability After Radical Prostatectomy. Eur Urol 2016;70:72-3 The Challenge of Assessing Work Disability2016Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, nr 1, s. 73-74Artikel i tidskrift (Övrigt vetenskapligt)
  • 44. Popiolek, Marcin
    et al.
    Rider, Jennifer R
    Andrén, Ove
    Andersson, Sven-Olof
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Regional Oncologic Center, University Hospital, Uppsala, Sweden.
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Natural History of Early, Localized Prostate Cancer: A Final Report from Three Decades of Follow-up2013Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 63, nr 3, s. 428-435Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Most localized prostate cancers are believed to have an indolent course. Within 15 yr of diagnosis, most deaths among men with prostate cancer (PCa) can be attributed to other competing causes. However, data from studies with extended follow-up are insufficient to determine appropriate treatment for men with localized disease.

    OBJECTIVE:

    To investigate the long-term natural history of untreated, early-stage PCa.

    DESIGN, SETTING, AND PARTICIPANTS:

    We conducted a population-based, prospective-cohort study using a consecutive sample of 223 patients with untreated, localized PCa from a regionally well-defined catchment area in central Sweden. All subjects were initially managed with observation. Androgen deprivation therapy was administered when symptomatic tumor progression occurred.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

    Based on >30 yr of follow-up, the main outcome measures were: progression-free, cause-specific, and overall survival, and rates of progression and mortality per 1000 person-years.

    RESULTS AND LIMITATIONS:

    After 32 yr of follow-up, all but 3 (1%) of the 223 men had died. We observed 90 (41.4%) local progression events and 41 (18.4%) cases of progression to distant metastasis. In total, 38 (17%) men died of PCa. Cause-specific survival decreased between 15 and 20 yr, but stabilized with further follow-up. All nine men with Gleason grade 8-10 disease died within the first 10 yr of follow-up, five (55%) from PCa. Survival for men with well-differentiated, nonpalpable tumors declined slowly through 20 yr, and more rapidly between 20 and 25 yr (from 75.2% [95% confidence interval, 48.4-89.3] to 25% [95% confidence interval, 22.0-72.5]). It is unclear whether these data are relevant for tumors detected by elevated prostate-specific antigen levels.

    CONCLUSIONS:

    Although localized PCa most often has an indolent course, local progression and distant metastasis can develop over the long term, even among patients considered low risk at diagnosis.

  • 45. Price, Alison J
    et al.
    Travis, Ruth C
    Appleby, Paul N
    Albanes, Demetrius
    Barricarte Gurrea, Aurelio
    Bjørge, Tone
    Bueno-de-Mesquita, H Bas
    Chen, Chu
    Donovan, Jenny
    Gislefoss, Randi
    Goodman, Gary
    Gunter, Marc
    Hamdy, Freddie C
    Johansson, Mattias
    King, Irena B
    Kühn, Tilman
    Männistö, Satu
    Martin, Richard M
    Meyer, Klaus
    Neal, David E
    Neuhouser, Marian L
    Nygård, Ottar
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Tell, Grethe S
    Trichopoulou, Antonia
    Tumino, Rosario
    Ueland, Per Magne
    Ulvik, Arve
    de Vogel, Stefan
    Vollset, Stein Emil
    Weinstein, Stephanie J
    Key, Timothy J
    Allen, Naomi E
    Circulating Folate and Vitamin B12 and Risk of Prostate Cancer: A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls.2016Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, nr 6, s. 941-951, artikel-id S0302-2838(16)00379-1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Folate and vitamin B12 are essential for maintaining DNA integrity and may influence prostate cancer (PCa) risk, but the association with clinically relevant, advanced stage, and high-grade disease is unclear.

    OBJECTIVE: To investigate the associations between circulating folate and vitamin B12 concentrations and risk of PCa overall and by disease stage and grade.

    DESIGN, SETTING, AND PARTICIPANTS: A study was performed with a nested case-control design based on individual participant data from six cohort studies including 6875 cases and 8104 controls; blood collection from 1981 to 2008, and an average follow-up of 8.9 yr (standard deviation 7.3). Odds ratios (ORs) of incident PCa by study-specific fifths of circulating folate and vitamin B12 were calculated using multivariable adjusted conditional logistic regression.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incident PCa and subtype by stage and grade.

    RESULTS AND LIMITATIONS: Higher folate and vitamin B12 concentrations were associated with a small increase in risk of PCa (ORs for the top vs bottom fifths were 1.13 [95% confidence interval (CI), 1.02-1.26], ptrend=0.018, for folate and 1.12 [95% CI, 1.01-1.25], ptrend=0.017, for vitamin B12), with no evidence of heterogeneity between studies. The association with folate varied by tumour grade (pheterogeneity<0.001); higher folate concentration was associated with an elevated risk of high-grade disease (OR for the top vs bottom fifth: 2.30 [95% CI, 1.28-4.12]; ptrend=0.001), with no association for low-grade disease. There was no evidence of heterogeneity in the association of folate with risk by stage or of vitamin B12 with risk by stage or grade of disease (pheterogeneity>0.05). Use of single blood-sample measurements of folate and B12 concentrations is a limitation.

    CONCLUSIONS: The association between higher folate concentration and risk of high-grade disease, not evident for low-grade disease, suggests a possible role for folate in the progression of clinically relevant PCa and warrants further investigation.

    PATIENT SUMMARY: Folate, a vitamin obtained from foods and supplements, is important for maintaining cell health. In this study, however, men with higher blood folate levels were at greater risk of high-grade (more aggressive) prostate cancer compared with men with lower folate levels. Further research is needed to investigate the possible role of folate in the progression of this disease.

  • 46.
    Robinson, David
    et al.
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden..
    Garmo, Hans
    Uppsala Univ Hosp, Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden.;Kings Coll London, Sch Med, Div Canc Studies, Canc Epidemiol Grp, London, England..
    Lissbrant, Ingela Franck
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Oncol, Gothenburg, Sweden..
    Widmark, Anders
    Umea Univ, Dept Radiat Sci, Oncol, Umea, Sweden..
    Pettersson, Andreas
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Gunnlaugsson, Adalsteinn
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, Lund, Sweden..
    Adolfsson, Jan
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden..
    Bratt, Ola
    Lund Univ, Dept Translat Med, Div Urol Canc, Lund, Sweden.;Cambridge Univ Hosp, CamPARI Clin, Dept Urol, Cambridge, England..
    Nilsson, Per
    Lund Univ, Skane Univ Hosp, Dept Oncol & Radiat Phys, Lund, Sweden..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Prostate Cancer Death After Radiotherapy or Radical Prostatectomy: A Nationwide Population-based Observational Study2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 73, nr 4, s. 502-511Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: There are no conclusive results from randomized trials on radiotherapy (RT) versus radical prostatectomy (RP) for prostate cancer. Numerous observational studies have suggested that RP is associated with a lower risk of prostate cancer death, but whether results have been biased due to limited adjustments for confounding factors is unknown.

    Objective: To compare the risk of prostate cancer death after RT versus RP.

    Design, setting, and participants: Nationwide population-based observational study of men in the Prostate Cancer data Base Sweden 3.0 who had undergone RT or RP between 1998 and 2012.

    Outcome measurements and statistical analysis: Prostate cancer deaths were compared. Hazard ratios (HRs) were calculated in Cox regression models, including clinical T stage, M stage, Gleason grade group, serum levels of prostate-specific antigen, proportion of biopsy cores with cancer, mode of detection, comorbidity, age, educational level, and civil status. Period analysis with left truncation was performed.

    Results and limitations: Primary treatment was RT or RP for 41 503 men. Treatment effect was associated with disease severity. In univariate analysis of RT versus RP, risk of prostate cancer death was higher after RT-low-and intermediate-risk cancer, HR 1.82 (95% confidence interval [CI]: 1.53-2.16), and high-risk cancer, HR 1.57 (95% CI: 1.33-1.85). After full adjustment in period analysis, this difference between the treatments was attenuated-low-and intermediate-risk cancer, HR 1.24 (95% CI: 0.97-1.58), and high-risk cancer, HR 1.03 (95% CI: 0.81-1.31). Confounding remained due to nonrandom allocation to treatment.

    Conclusions: In comparison with previous studies, the difference in prostate cancer mortality after RT and RP was much smaller.

    Patient summary: The difference in prostate cancer mortality after contemporary radiotherapy and radical prostatectomy was small in contrast to previous studies, indicating that potential side effects should be more emphasized when selecting treatment.

  • 47. Rosenblatt, Robert
    et al.
    Sherif, Amir
    Rintala, Erkki
    Wahlqvist, Rolf
    Ullén, Anders
    Nilsson, Sten
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Pathologic Downstaging Is a Surrogate Marker for Efficacy and Increased Survival Following Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Urothelial Bladder Cancer2012Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 61, nr 6, s. 1229-1238Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Characterising responders to neoadjuvant chemotherapy (NAC) is important to minimise overtreatment and the unnecessary delay of definitive treatment of urothelial urinary bladder cancer.

    OBJECTIVE: To assess the effect of NAC on tumour downstaging and overall survival.

    DESIGN, SETTING, AND PARTICIPANTS: A total of 449 patients from the randomised prospective Nordic Cystectomy Trials 1 and 2 were analysed retrospectively. Eligible patients were defined as T2-T4aNXM0 preoperatively and pT0-pT4aN0-N+M0 postoperatively. The median follow-up time was 5 yr.

    INTERVENTION: The experimental arm consisted of cisplatin-based NAC; the control arm consisted of cystectomy only.

    MEASUREMENTS: The primary outcome was tumour downstaging defined as pathologic TNM less than clinical TNM. Different downstaging thresholds were applied: complete downstaging (CD) (pT0N0), noninvasive downstaging (NID) (pT0/pTis/pTaN0), and organ confinement (OC) (≤pT3aN0). Downstaging rates and nodal status were compared between the study arms using the chi-square test. Secondary outcome was overall survival (OS) stratified by treatment arm, downstaging categories, and clinical stages, analysed by the Kaplan-Meier method. The following covariates were tested as prognostic factors in univariate and multivariate analyses using the Cox regression method: age, sex, clinical stage, pN status, NAC, CD, NID, and OC.

    RESULTS AND LIMITATIONS: Downstaging rates increased significantly in the NAC arm independent of the downstaging threshold. The impact was more prominent in clinical T3 tumours, with a near threefold increase in CD tumours. The combination of CD and NAC showed an absolute risk reduction of 31.1% in OS at 5 yr compared with CD controls. The combination of NAC and CD revealed a hazard ratio of 0.32 compared with 1.0 for the combination of no NAC and no CD. Limitations were the retrospective approach and uncertain clinical TNM staging.

    CONCLUSIONS: Survival benefits of NAC are reflected in downstaging of the primary tumour. Chemo-induced downstaging might be a potential surrogate marker for OS.

  • 48. Schultz, Iman J
    et al.
    Wester, Kenneth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Straatman, Huub
    Kiemeney, Lambertus A
    Babjuk, Marko
    Mares, Jaroslav
    Willems, Johannes L
    Swinkels, Dorine W
    Witjes, J Alfred
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    de Kok, Jacques B
    Gene expression analysis for the prediction of recurrence in patients with primary Ta urothelial cell carcinoma2007Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 51, nr 2, s. 416-423Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives

    The individual recurrence-free period after primary surgery of patients with Ta urothelial cell carcinoma (UCC) cannot be predicted accurately. This study aims at discriminating between patients with primary Ta UCC and long or short recurrence-free periods.

    Methods

    We investigated mRNA expression of 23 genes in 44 primary Ta tumours (23 and 21 tumours were from patients with long [≥4 yr] or short [≤2 yr] recurrence-free periods, respectively), using real-time quantitative polymerase chain reaction. The genes were selected from previously published studies and showed a relationship with tumour recurrence in patients with UCC.

    Results

    Differential mRNA expression between the two patient groups indicated statistical significance only for the gene survivin (p = 0.0011). Its recurrence predictive value could not be increased by a combination with any of the other genes. Comparison of the receiver operating characteristic curves for survivin expression between patients with long or short recurrence-free intervals revealed an area under the curve of 0.79 (95%CI, 0.65–0.92). Using the median expression (0.84) as cut-off level, survivin identified 71.4% (95%CI, 47.8–88.7) and 69.6% (95%CI, 47.1–86.8) of the patients with long or short recurrence-free periods, respectively.

    Conclusions

    Our study identifies survivin as the most promising candidate to distinguish between patients with primary Ta UCC and long or short recurrence-free intervals. Therefore, survivin mRNA expression analysis might help the urologist to individualise patient treatment and prevent unnecessary cystoscopies in a subgroup of these patients.

  • 49. Simpkin, Andrew J
    et al.
    Tilling, Kate
    Martin, Richard M
    Lane, J Athene
    Hamdy, Freddie C
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Neal, David E
    Metcalfe, Chris
    Donovan, Jenny L
    Systematic Review and Meta-analysis of Factors Determining Change to Radical Treatment in Active Surveillance for Localized Prostate Cancer.2015Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 67, nr 6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT: Many men with clinically localized prostate cancer are being monitored as part of active surveillance (AS) programs, but little is known about reasons for receiving radical treatment.

    OBJECTIVES: A systematic review of the evidence about AS was undertaken, with a meta-analysis to identify predictors of radical treatment.

    EVIDENCE ACQUISITION: A comprehensive search of the Embase, MEDLINE and Web of Knowledge databases to March 2014 was performed. Studies reporting on men with localized prostate cancer followed by AS or monitoring were included. AS was defined where objective eligibility criteria, management strategies, and triggers for clinical review or radical treatment were reported.

    EVIDENCE SYNTHESIS: The 26 AS cohorts included 7627 men, with a median follow-up of 3.5 yr (range of medians 1.5-7.5 yr). The cohorts had a wide range of inclusion criteria, monitoring protocols, and triggers for radical treatment. There were eight prostate cancer deaths and five cases of metastases in 24,981 person-years of follow-up. Each year, 8.8% of men (95% confidence interval 6.7-11.0%) received radical treatment, most commonly because of biopsy findings, prostate-specific antigen triggers, or patient choice driven by anxiety. Studies in which most men changed treatment were those including only low-risk Gleason score 6 disease and scheduled rebiopsies.

    CONCLUSIONS: The wide variety of AS protocols and lack of robust evidence make firm conclusions difficult. Currently, patients and clinicians have to make judgments about the balance of risks and benefits in AS protocols. The publication of robust evidence from randomized trials and longer-term follow-up of cohorts is urgently required.

    PATIENT SUMMARY: We reviewed 26 studies of men on active surveillance for prostate cancer. There was evidence that studies including men with the lowest risk disease and scheduled rebiopsy had higher rates of radical treatment.

  • 50.
    Stattin, Pär
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ Hosp, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Bratt, Ola
    Lund Univ, Div Urol Canc, Dept Translat Med Urol, Lund, Sweden.;Cambridge Univ Hosp, Dept Urol, CamPARI Clin, Cambridge, England..
    Reply to Glen Denmer Santok and Koon Ho Rha's Letter to the Editor re: Par Stattin, Fredrik Sandin, Frederik Birkebaek Thomsen, et al. Association of Radical Local Treatment with Mortality in Men with Very High-risk Prostate Cancer: A Semiecologic, Nationwide, Population-based Study. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2016.07.0232017Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, nr 4, s. E115-E116Artikel i tidskrift (Övrigt vetenskapligt)
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