Search

Objective: Active surveillance (AS) is recommended for low-risk and some favourable intermediate-risk prostate cancers, but criteria for AS and deferred treatment have changed over time. We assessed time trends for the use of AS and deferred treatment., Material and Methods: Nationwide Swedish register study of 76,191 men diagnosed with low- or intermediate-risk localised prostate cancer from 2008 to 2020. This study presents the proportion of men starting on AS, their clinical characteristics and proportion having deferred treatment. Cox regression was used to calculate hazard ratios for deferred treatment. Subgroup analyses were performed for men < 60 years with Charlson Comorbidity Index 0., Results: Overall use of AS increased from 2008-2010 to 2017-2020: any low-risk: 40% to 81%, very low-risk disease: 57% to 91%, other low-risk: 37% to 77% and intermediate-risk: 16% to 20%. The relative increase in the use of AS in men < 60 years with Charlson Comorbidity Index 0 was similar to, or greater than, the increase overall. A total of 28,211 men started on AS. The crude proportions of men receiving deferred treatment were relatively stable over time; 2017-2020: very low-risk disease 8%, other low-risk 16% and intermediate-risk 23%. After adjustment for clinical characteristics, deferred treatment within 2 years decreased over time for very low-risk, was stable for other low-risk and increased for intermediate-risk cancer., Conclusions: The use of AS greatly increased over time, not least amongst younger healthy men, whereas the use of deferred treatment was relatively stable. AS has been increasingly accepted as a safe approach for localised, favourable-risk prostate cancer.

Objective: To examine associations between objective signs of progression (triggers) and transition from active surveillance (AS) to radical treatment for prostate cancer (PC)., Patients and Methods: This case-control study included men with low- or favourable intermediate-risk PC in the region of Halland, with data from The National Prostate Cancer Register (NPCR), Sweden, starting AS between 2008 and 2020. Cases were men who transitioned to radical treatment. For each case, 10 controls who remained in AS were selected without further matching. Triggers for transition to treatment were histopathological progression, magnetic resonance imaging (MRI) progression and increases in prostate-specific antigen (PSA) levels. We compared the probabilities for triggers between cases and controls, in 2008-2014 and 2015-2020, using logistic regression., Results: Amongst 846 men, we identified 98 cases in 2008-2014 and 172 cases in 2015-2020. Histopathological progression was associated with transition, most strongly in the later period (2008-2014: odds ratios [OR] 6.88, 95% confidence interval [CI] 3.69-12.80; and 2015-2020: OR 75.29, 95% CI 39.60-143.17). MRI progression was associated with transition in 2015-2020 (OR 6.38, 95% CI 2.70-15.06), whereas an increase in PSA was weakly associated with transition in the early period. The absence of triggers was associated with no transition (2008-2014: OR 0.24, 95% CI 0.15-0.40, and 2015-2020: OR 0.09, 95% CI 0.06-0.14). The probability of no trigger was 27% in cases 2015-2020., Conclusion: The increase in association between histopathological trigger and transition to treatment indicates increased quality of AS. Still, amongst men treated from 2015 to 2020, 27% transitioned without any trigger.

Background: A diagnosis of prostate cancer (PC) may cause psychosocial distress that worsens quality of life; however, long-term mental health outcomes are unclear., Objective: To determine the long-term risks of major depression and death by suicide in a large population-based cohort., Design, Setting, and Participants: This was a national cohort study of 180 189 men diagnosed with PC during 1998-2017 and 1 801 890 age-matched, population-based, control men in Sweden., Outcome Measurements and Statistical Analysis: Major depression and death by suicide were ascertained from nationwide outpatient, inpatient, and death records up to 2018. Cox regression was used to compute hazard ratios (HRs) adjusted for sociodemographic factors and comorbidities. Subanalyses assessed differences by PC treatment during 2005-2017., Results and Limitations: Men diagnosed with high-risk PC had higher relative rates of major depression (adjusted HR [aHR] 1.82, 95% confidence interval [CI] 1.75-1.89) and death by suicide (aHR 2.43, 95% CI 2.01-2.95). These associations persisted for ≥10 yr after PC diagnosis. The relative increase in major depression was lower among those treated with radiation (aHR 1.44, 95% CI 1.31-1.57) or surgery (aHR 1.60, 95% CI 1.31-1.95) in comparison to androgen deprivation therapy (ADT) alone (aHR 2.02, 95% CI 1.89-2.16), whereas the relative rate of suicide death was higher only among those treated solely with ADT (aHR 2.83, 95% CI 1.80-4.43). By contrast, men with low- or intermediate-risk PC had a modestly higher relative rate of major depression (aHR 1.19, 95% CI 1.16-1.23) and higher relative rate of suicide death at 3-12 mo after PC diagnosis (aHR 1.88, 95% CI 1.11-3.18) but not across the entire follow-up period (aHR 1.02, 95% CI 0.84-1.25). This study was limited to Sweden and will need replication in other populations., Conclusions: In this large cohort, high-risk PC was associated with substantially higher relative rates of major depression and death by suicide, which persisted for ≥10 yr after PC diagnosis. PC survivors need close follow-up for timely detection and treatment of psychosocial distress., Patient Summary: In a large Swedish population, men with aggressive prostate cancer had higher long-term relative rates of depression and suicide., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: Although surveillance after radical prostatectomy routinely includes repeated prostate specific antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be shortened for many patients without increasing the risk of prostate cancer death. We investigated the long-term probabilities of PSA recurrence, metastases and prostate cancer death in patients without biochemical recurrence five and 10 years after radical prostatectomy., Design: Prospective cohort study. Stratification by Gleason score (≤3+4=7 or ≥4+3=7), pathological tumour stage (pT2 or ≥pT3) and negative or positive surgical margins., Setting: Between 1989 and 1998, 14 urological centres in Scandinavia randomised patients to the Scandinavian Prostate Cancer Group study number 4 (SPCG-4) trial., Participation: All 306 patients from the SPCG-4 trial who underwent radical prostatectomy within 1 year from inclusion were eligible. Four patients were excluded due to surgery-related death (n=1) or salvage radiotherapy or hormonal treatment within 6 weeks from surgery (n=3)., Primary Outcome Measures: Cumulative incidences and absolute differences in metastatic disease and prostate cancer death., Results: We analysed 302 patients with complete follow-up during a median of 24 years. Median preoperative PSA was 9.8 ng/mL and median age was 65 years. For patients without biochemical recurrence 5 years after radical prostatectomy the 20-year probability of biochemical recurrence was 25% among men with Gleason score ≤3+4=7 and 57% among men with Gleason score ≥4+3=7; the probabilities for metastases were 0.8% and 17%; and for prostate cancer death 0.8% and 12%, respectively. The long-term probabilities were higher for pT ≥3 versus pT2 and for positive versus negative surgical margins. Limitations include small size of the cohort., Conclusion: Many patients with favourable histopathology without biochemical recurrence 5 years after radical prostatectomy could stop follow-up earlier than 10 years after radical prostatectomy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Importance: The long-term outcomes among men with prostate cancer (PC) whose disease is managed with active surveillance (AS) remains unknown., Objective: To develop a simulation model with a 30-year follow-up for men with PC managed with AS., Design, Setting, and Participants: In this cohort study, a state transition model was created using data from Prostate Cancer data Base Sweden (PCBaSe) on 23 655 men diagnosed with PC and managed with deferred treatment to estimate treatment trajectories. A simulation was performed with 100 000 men in each combination of age at diagnosis, Charlson Comorbidity Index, and PC risk with a follow-up of 30 years., Main Outcomes and Measures: Death from PC and death from other causes were estimated, and the proportion of time without active PC treatment was assessed until date of death or age 85 years., Results: This study included 23 655 men from PCBaSe with a median age at diagnosis of 69 years (IQR, 64-74 years). Of these, 16 177 men underwent active surveillance for PC and 7478 underwent watchful waiting. The proportion of men who were diagnosed at age 55 years and died of PC before age 85 years was 9% for very low-risk PC, 13% for low-risk PC, and 15% for intermediate-risk PC. Among men with a Charlson Comorbidity Index of 0 who were diagnosed at age 70 years, the corresponding percentages were 3%, 6%, and 7%, respectively. The mean proportion of remaining life-years without active PC treatment for men diagnosed at age 55 years was 12 of 25 years (48%) for very low-risk PC, 9 of 25 years (36%) for low-risk PC, and 7 of 25 (29%) for intermediate-risk PC. For men aged 70 years, the corresponding numbers were 10 of 13 years (77%), 9 of 13 years (66%), and 8 of 13 years (60%), respectively. Men with intermediate-risk PC who were younger than 60 years at diagnosis had a high risk of PC death (12%-15%) and fewer remaining life-years without active PC treatment (29%-33%). In contrast, men with low-risk PC who were older than 65 years at diagnosis had a lower risk of PC death (3%-5%) and more remaining life-years without active PC treatment (62%-77%)., Conclusions and Relevance: The findings of this Swedish cohort study suggest that active surveillance may be a safe strategy for disease management among men with PC who were older than 65 years at diagnosis.

Objectives: To predict castration-resistant prostate cancer (CRPC) and prostate cancer (Pca) death by use of clinical variables at Pca diagnosis and PSA levels after start of gonadotropin-releasing hormone agonists (GnRH) in men with non-metastatic castration sensitive prostate cancer (nmCSPC). Materials and Methods: PSA values for 1603 men with nmCSPC in the National Prostate Cancer Register of Sweden who received GnRH as primary treatment were retrieved from Uppsala-Örebro PSA Cohort and Stockholm PSA and Biopsy Register. All men had measured PSA before ( pre-GnRH PSA ) and 3-6 months after ( post-GnRH PSA ) date of start of GnRH. Unadjusted and adjusted Cox models were used to predict CRPC by PSA levels. PSA levels and ISUP grade were used to construct a risk score to stratify men by tertiles according to risk of CRPC and Pca death. Results: 788 (49%) men reached CRPC and 456 (28%) died of Pca during follow-up. Post-GnRH PSA predicted CRPC regardless of pre-GnRH PSA . CRPC risk increased with higher post-GnRH PSA , HR 4.7 (95% CI: 3.4-6.7) for PSA > 16 ng/mL vs 0-0.25 ng/mL and with ISUP grade, HR 3.7 (95%: 2.5-5.4) for ISUP 5 vs ISUP 1. Risk of Pca death in men above top vs bellow bottom tertile of post-GnRH PSA and ISUP grade was HR 4.1 (95% CI: 3.0-5.5). Conclusion: A risk score based on post-GnRH PSA and ISUP grade could be used for early identification of a target group for future clinical trials on additional therapy to GnRH.

Background: Trials of cancer screening present results in terms of deaths prevented, but metastasis is also a key endpoint that screening seeks to prevent. We developed a framework for projecting overall (de novo and progressive) metastases prevented in a screening trial using prostate cancer screening as a case study., Methods: Mechanistic simulation model in which screening shifts a fraction of cases that would be metastatic at diagnosis to being non-metastatic. This shift increases the incidence of non-overdiagnosed, organ-confined cases. We use estimates of the risk of metastatic progression for these cases to project how many progress to metastasis after diagnosis and tally the projected de novo and progressive metastatic cases with and without screening. We use data on stage shift from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and data on the risk of metastatic progression from the Scandinavian Prostate Cancer Group-4 trial. We estimate the relative risk and absolute risk reductions in metastatic disease at diagnosis and compare these with reductions in overall metastases., Results: Assuming no effect of screening beyond initial stage shift at diagnosis, the model projects a 43% reduction in metastasis at diagnosis but a 22% reduction in the cumulative probability of metastasis over 12 years in favor of screening. These results are consistent with the empirical findings from the ERSPC., Conclusion: Any reduction in metastatic disease at diagnosis under screening is likely to be an overly optimistic predictor of the impact of screening on overall metastasis and disease-specific mortality.

Importance: The diagnostic activity for prostate cancer has increased during the past decades. However, the benefit and harm of the increased diagnostic activity have not been quantified in detail for a country or a large region., Objective: The aim of this study was to evaluate and quantify the association between increases in diagnostic activity driven by prostate-specific antigen testing and incidence of prostate cancer diagnosis, treatment, and mortality., Design, Setting, and Participants: This cohort study used the Proxy-Based Risk-Stratified Incidence Simulation Model-Prostate Cancer to examine observed data on all Swedish men with prevalent prostate cancer and compare them with a corresponding, hypothetical, simulated scenario with more restrictive diagnostic activity. All men aged 40 to 100 years living in Sweden during the time period 1996 to 2016 with incident and prevalent prostate cancer were included. The second scenario is the corresponding, hypothetical, simulated scenario where diagnostic activity remained constant as of 1996 (the beginning of the prostate-specific antigen testing era) throughout the study period., Exposures: High or low diagnostic activity for prostate cancer., Main Outcomes and Measures: Incidence of prostate cancer diagnosis, treatment (deferred treatment, curative treatment, and hormonal treatment), and prostate cancer mortality., Results: During the study period from 1996 to 2016, 188 884 men were diagnosed with prostate cancer at a median (interquartile range) age of 71 (64-77) years. Compared with the low-diagnostic activity scenario, in the high-diagnostic activity scenario, the number of men diagnosed with prostate cancer was 48% higher (423 vs 286 [95% CI, 271-302] per 100 000 men per year), 148% more men were diagnosed with low- or intermediate-risk cancer (221 vs 89 [95% CI, 73-105] per 100 000 men per year), and 108% more men received curative treatment (152 vs 73 [95% CI: 66-85] per 100 000 men per year). There were up to 15% fewer prostate cancer deaths in the scenario with high-diagnostic activity (incidence rate ratio, 0.85; 95% CI, 0.82-0.88)., Conclusions and Relevance: This study's results suggest that increased prostate-specific antigen testing and diagnostic activity are associated with a larger number of men being diagnosed with prostate cancer, predominately with low- and intermediate-risk disease. The increased diagnostic activity was associated with a 2-fold increase in curative treatment and a modest decrease in mortality.

Objective: Long-term information on lifestyle changes among prostate survivors is lacking. In this nationwide, population-based study we investigated the prevalence of lifestyle changes, factors associated with lifestyle changes and associations between lifestyle changes and general quality of life., Methods: All men registered in the National Prostate Cancer Register of Sweden diagnosed in 2008 with low-risk prostate cancer at age 70 years or younger were sent a questionnaire. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals for factors potentially associated with lifestyle change., Results: Out of 1288, 1720 men (75%) were responded. A total of 279 (22%) reported a positive lifestyle change regarding diet or exercise. Poor functional outcomes after treatment was associated with exercising less (OR 1.6, 95% CI 1.2-2.1) and less interest in social activities and relationships (OR 1.8, 95% CI 1.5-2.1). Men who exercised more (OR 7.9, 95% CI 4.4-14) and men who had an increased interest in relationships and social activities (OR 5.2, 95% CI 2.1-13) reported higher general quality of life., Conclusions: A considerable proportion of men reported making positive lifestyle changes after the prostate cancer diagnosis. The time after diagnosis may be a teachable moment that facilitates lifestyle interventions. Poor functional outcomes after treatment may reduce the willingness to engage in positive lifestyle change, which need be considered when supporting men after treatment. Men who made a positive lifestyle change, regardless of whether it was exercise or regarding relationships and social activities more often reported a high level of general quality of life., (© 2020 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Background: Organized PSA testing for asymptomatic men aged 50-74 years will be implemented in Sweden to reduce opportunistic testing in groups who will not benefit. The aim of this study was to describe the opportunistic PSA testing patterns in a Swedish region before the implementation of organized PSA testing programs., Method: We included all men in the Uppsala-Örebro health care region of Sweden who were PSA tested between 1 July 2012 and 30 June 2014. Information regarding previous PSA testing, prostate cancer diagnosis, socioeconomic situation, surgical procedures and prescribed medications were collected from population-wide registries to create the Uppsala-Örebro PSA cohort (UPSAC). The cohort was divided into repeat and single PSA testers. The background population used for comparison consisted of men 40 years or older, living in the Uppsala-Örebro region during this time period., Results: Of the adult male population in the region, 18.1% had undergone PSA testing. Among men over 85 years old 21% where PSA tested. In our cohort, 62.1% were repeat PSA testers. Of men with a PSA level ≤1µg/l 53.8% had undergone repeat testing. Prostate cancer was found in 2.7% and 4.8% of the repeat and single testers, respectively., Conclusion: Every fifth man in the male background population was PSA tested. Repeated PSA testing was common despite low PSA values. As repeated PSA testing was common, especially among older men who will not be included in organized testing, special measures to change the testing patterns in this group may be required.

Background: Androgen deprivation therapy (ADT) is a non-curative but essential treatment of prostate cancer with severe side effects. Therefore, both over- and underuse should be avoided. We investigated adherence to guidelines for ADT following radical prostatectomy through Swedish population-based data. Material and methods: We used the database Uppsala/Örebro PSA cohort (UPSAC) to study men with localised or locally advanced prostate cancer at diagnosis (clinical stage T1-T3, N0-NX, M0-MX, and prostate-specific antigen (PSA) <50 ng/ml) who underwent radical prostatectomy 1997-2012. 114 men were treated with ADT and selected as cases; 1140 men with no ADT at the index date were selected as controls within 4-year strata of year of radical prostatectomy. All men with a biochemical recurrence and a PSA doubling time <12 months and/or a Gleason score of 8-10 were considered to have an indication for ADT according to the European Association of Urology (EAU) guidelines. Results: No indication for ADT was found in 37% of the cases. Among these, 88% had clinical stage T1-2 at diagnosis, 57% had a biopsy Gleason score 2-6, 98% had an expected remaining lifetime over 10 years, 12% received castration, and 88% received antiandrogen monotherapy. 2% of controls were found to have an indication for ADT, and 96% of these had an expected remaining lifetime over 10 years. Conclusion: Our results indicate that overtreatment with ADT after radical prostatectomy is common, whereas undertreatment is unusual. Interventions to improve adherence to guidelines are needed to avoid unnecessary side-effects and long treatment durations with ADT.

Background: Active surveillance (AS) is an accepted means of managing low-risk prostate cancer. Because of the rarity of downstream events, data from existing AS cohorts cannot yet address how differences in surveillance intensity affect metastasis and mortality. This study projected the comparative benefits of different AS schedules in men diagnosed with prostate cancer who had Gleason score (GS) ≤6 disease and risk profiles similar to those in North American AS cohorts., Methods: Times of GS upgrading were simulated based on AS data from the University of Toronto, Johns Hopkins University, the University of California at San Francisco, and the Canary Pass Active Surveillance Cohort. Times to metastasis and prostate cancer death, informed by models from the Scandinavian Prostate Cancer Group 4 trial, were projected under biopsy surveillance schedules ranging from watchful waiting to annual biopsies. Outcomes included the risk of metastasis, the risk of death, remaining life-years (LYs), and quality-adjusted LYs., Results: Compared with watchful waiting, AS biopsies reduced the risk of prostate cancer metastasis and prostate cancer death at 20 years by 1.4% to 3.3% and 1.0% to 2.4%, respectively; and 5-year biopsies reduced the risk of metastasis and prostate cancer death by 1.0% to 2.4% and 0.6% to 1.6%, respectively. There was little difference between annual and 5-year biopsy schedules in terms of LYs (range of differences, 0.04-0.16 LYs) and quality-adjusted LYs (range of differences, -0.02 to 0.09 quality-adjusted LYs)., Conclusions: Among men diagnosed with GS ≤6 prostate cancer, obtaining a biopsy every 3 or 4 years appears to be an acceptable alternative to more frequent biopsies. Reducing surveillance intensity for those who have a low risk of progression reduces the number of biopsies while preserving the benefit of more frequent schedules., (© 2019 American Cancer Society.)

Objective: Knowledge about factors influencing choice of and adherence to active surveillance (AS) for prostate cancer (PC) is scarce. We aim to identify which factors most affected choosing and adhering to AS and to quantify their relative importance., Design, Setting and Participants: In 2015, we sent a questionnaire to all Swedish men aged ≤70 years registered in the National Prostate Cancer Register of Sweden who were diagnosed in 2008 with low-risk PC and had undergone prostatectomy, radiotherapy or started on AS., Outcome Measurements and Statistical Analysis: Logistic regression was used to calculate ORs with 95% CIs for factors potentially affecting choice and adherence to AS., Results: 1288 out of 1720 men (75%) responded, 451 (35%) chose AS and 837 (65%) underwent curative treatment. Of those starting on AS, 238 (53%) diverted to treatment within 7 years. Most men (83%) choose AS because 'My doctor recommended AS'. Factors associated with choosing AS over treatment were older age (OR 1.81, 95% CI 1.29 to 2.54), a Charlson Comorbidity Index >2 (OR 1.50, 95% CI 1.06 to 2.13), being unaccompanied when notified of the cancer diagnosis (OR 1.45, 95% CI 1.11 to 1.89). Men with a higher prostate-specific antigen (PSA) at the time of diagnosis were less likely to adhere to AS (OR 0.26, 95% CI 0.10 to 0.63). The reason for having treatment after initial AS was 'the PSA level was rising' in 55% and biopsy findings in 36%., Conclusions: A doctor's recommendation strongly affects which treatment is chosen for men with low-risk PC. Rising PSA values were the main factor for initiating treatment for men on AS. These findings need be considered by healthcare providers who wish to increase the uptake of and adherence to AS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent., Methods and Analysis: A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, ≤T2a, prostate-specific antigen (PSA) <15 ng/mL, PSA density ≤0.2 ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10 mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled., Ethics and Dissemination: Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals., Trial Registration Number: NCT02914873., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate if results in terms of absolute risk in mature randomised trials are relevant for contemporary decision-making. To do so, we compared the outcome for men in the radical prostatectomy (RP) arm of the Scandinavian Prostate Cancer Group Study number 4 (SPCG-4) randomised trial with matched men treated in a contemporary era before and after compensation for the grade migration and grade inflation that have occurred since the 1980s., Patients and Methods: A propensity score-matched analysis of prostate cancer mortality and all-cause mortality in the SPCG-4 and matched men in the National Prostate Cancer Register (NPCR) of Sweden treated in 1998-2006 was conducted. Cumulative incidence of prostate cancer mortality and all-cause mortality was calculated. Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for a matching on original Gleason Grade Groups (GGG) and second, matching with GGG increased one unit for men in the NPCR., Results: Matched men in the NPCR treated in 2005-2006 had half the risk of prostate cancer mortality compared to men in the SPCG-4 (HR 0.46, 95% CI 0.19-1.14). In analysis of men matched on an upgraded GGG in the NPCR, this difference was mitigated (HR 0.73, 95% CI 0.36-1.47)., Conclusions: Outcomes after RP for men in the SPCG-4 cannot be directly applied to men in the current era, mainly due to grade inflation and grade migration. However, by compensating for changes in grading, similar outcomes after RP were seen in the SPCG-4 and NPCR. In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Background: Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term follow-up is sparse., Methods: We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model., Results: By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer)., Conclusions: Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer. (Funded by the Swedish Cancer Society and others.).

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., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Men with prostate cancer experience adjuvant androgen deprivation therapy (ADT) differently., Objective: To evaluate the effect of ADT on quality of life (QoL), patients' experience of clinical check-ups, and differences in cancer information as explanatory factors., Design, Setting, and Participants: A study-specific questionnaire was sent to all men randomized in the SPCG-4 trial to radical prostatectomy (RP) or watchful waiting (WW) still alive (400/695) and a control group of 281 men., Intervention: ADT., Outcome Measurements and Statistical Analysis: Self-assessed QoL, worry at clinical check-ups, and amount of information received. Estimated relative risks with associated 95% confidence intervals (CI) for risk comparisons between groups using a log-binomial regression., Results and Limitations: The SPCG-4 men had median follow-up of 12.2 yr and median age of 77.0 yr; 26% in the RP group and 40% in the WW group received ADT treatment. High QoL for men without ADT was 36% for the RP group, 44% for the WW group, and 45% for the control group. High QoL for men with ADT was 30% for the RP group and 20% for the WW group. Among men with ADT, those in the WW group received significantly less information about the disease than men in the RP group. Receiving no or little information about prostate cancer was reported by 17% of patients in the RP group and 39% in the WW group among men receiving ADT (relative risk 0.44, 95% CI 0.22-0.89). At clinical check-ups, men treated with ADT had significantly higher levels of worry, regardless of study group, than men without ADT. Limitations include the lack of longitudinal data and a low number of men receiving ADT in the RP group., Conclusions: Men on WW without ADT reported high QoL comparable to that for men without prostate cancer. ADT treatment in the WW group was associated with the lowest scores for all psychological parameters, and these men reported that they were least informed about prostate cancer and its consequences., Patient Summary: Good communication and information from caregivers are associated with less negative psychological effects at prostate cancer progression., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Information about how men with prostate cancer (PC) experience their medical care and factors associated with their overall satisfaction with care (OSC) is limited., Objective: To investigate OSC and factors associated with OSC among men with low-risk PC., Design, Setting, and Participants: Men registered in the National Prostate Cancer Register of Sweden as diagnosed in 2008 with low-risk PC at the age of ≤70 yr who had undergone radical prostatectomy (RP), radiotherapy (RT), or started on active surveillance (AS) were invited in 2015 to participate in this nationwide population-based survey (n=1720)., Outcome Measurements and Statistical Analysis: OSC data were analysed using ordinal logistic regression. Odds ratios (ORs) were calculated for comparisons between the highest and lowest possible response categories., Results and Limitations: A total of 1288 men (74.9%) responded. High OSC was reported by 958 (74.4%). Factors associated with high OSC were high participation in decision-making (OR 4.18, 95% confidence interval [CI] 2.61-6.69), receiving more information (OR 11.1, 95% CI 7.97-15.6), high-quality information (OR 7.85, 95% CI 5.46-11.3), access to a nurse navigator (OR 1.80, 95% CI 1.44-2.26), and better functional outcomes (defined as 25 points higher on the EPIC-26 questionnaire; OR 1.34, 95% CI 1.21-1.48). OSC was not affected by whether a doctor or specialist nurse conducted follow-up (OR 0.84, 95% CI 0.66-1.07). These findings were similar across treatment groups. Men who had undergone RP or RT reported high OSC more often than men on AS (78.2% vs 84.0% vs 72.6%), high participation in decision-making (70.5% vs 64.5% vs 49.2%), and having received more information (40.5% vs 45.8% vs 28.6%), and were less likely to believe they would die from PC (3.8% vs 3.9% vs 8.0%). Limitations include the nonrandomised retrospective design and potential recall bias., Conclusions: Information and participation in decision-making, as well as access to a nurse navigator, are key factors for OSC, regardless of treatment. Men on AS need more information about their treatment and need to participate more in decision-making. OSC was as high among men who had nurse-led follow-up as among men who had doctor-led follow-up., Patient Summary: Information about how men with low-risk prostate cancer experience their medical care is limited. In this nationwide population-based study we found that information and participation in decision-making as well as access to a nurse navigator are key factors for satisfaction regardless of treatment. Men who are being closely watched for prostate cancer without immediate curative treatment need more information than they now receive and need to participate more in decision-making than they currently do., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Symptoms of terminal cancer have previously been reported as undertreated. The aim of this study was to assess the use of palliative medications before death from prostate cancer., Methods: This Swedish register study included men who died from 2009 to 2012 with prostate cancer as the underlying cause of death. We assessed the proportion who collected a prescription of androgen deprivation therapy, non-steroidal anti-inflammatory drugs, paracetamol, opioids, glucocorticoids, antidepressants, anxiolytics and sedative-hypnotics and the differences in treatment related to age, time since diagnosis, educational level, close relatives and comorbidities. Data were collected from 3 years before death from prostate cancer., Results: We included 8326 men. The proportion who received opioids increased from 30% to 72% during the last year of life, and 67% received a strong opioid at the time of death. Antidepressants increased from 13% to 22%, anxiolytics from 9% to 27% and sedative-hypnotics from 21% to 33%. Men without close relatives and older men had lower probability to receive opioids (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.47-0.66 for >85 years versus <70 years) and (OR 0.78, 95% CI: 0.66-0.92 for unmarried without children versus married with children)., Conclusion: Our results represent robust epidemiological data from Sweden for comparison of palliative care quality between countries. The findings indicate that men without close relatives and older men are disadvantaged with respect to the treatment of cancer pain and need closer attention from health care providers and highlight the importance to identify psychological distress in terminal prostate cancer., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to evaluate the additional value of magnetic resonance imaging-targeted biopsy (MRI-TB) to standard transrectal ultrasound-guided biopsy (SB) for detection of clinically significant prostate cancer (PCa). An additional aim was to compare the biopsy results to MRI evaluation using a Likert scale., Materials and Methods: Patients with newly diagnosed localized PCa (n = 53) by clinical routine SB were prospectively included. The majority of the patients were scheduled for curative therapy before enrollment. The patients underwent multiparametric MRI (mpMRI) at 3 T using an endorectal coil followed by two MRI-TBs, using ultrasound with cognitive fusion. All included patients underwent MRI-TB, even those who had low to very low suspicion of significant PCa on mpMRI. The detection rate of significant cancer on SB versus SB + MRI-TB was compared in the 53 included patients and with whole-mounted histopathology as reference in 34 cases. Comparison of the biopsy results to MRI evaluation and interreader agreement calculation of five-point Likert score evaluation were performed., Results: In total, 32 significant (Gleason ≥7) PCa were detected by SB, while SB + MRI-TB detected an additional five significant PCa. MRI-TB alone detected 20 and missed 17 significant PCa. Ten of the significant PCa cases missed by MRI-TB had a Likert score of 3 or lower. Interreader agreement using the Likert scale was high, with a kappa value of 0.77 (95% confidence interval 0.63-0.92, p < 0.0001)., Conclusion: Detection of significant PCa increased by adding MRI-TB to SB. This may not be of enough clinical value to justify the use of targeted biopsies in this patient group.

Objective: To determine whether there are differences in prostate-specific antigen (PSA) levels at diagnosis or changes in PSA levels between US and European populations of men with and without prostate cancer (PCa)., Subjects and Methods: We analysed repeated measures of PSA from six clinically and geographically diverse cohorts of men: two cohorts with PSA-detected PCa, two cohorts with clinically detected PCa and two cohorts without PCa. Using multilevel models, average PSA at diagnosis and PSA change over time were compared among study populations., Results: The annual percentage PSA change of 4-5% was similar between men without cancer and men with PSA-detected cancer. PSA at diagnosis was 1.7 ng/mL lower in a US cohort of men with PSA-detected PCa (95% confidence interval 1.3-2.0 ng/mL), compared with a UK cohort of men with PSA-detected PCa, but there was no evidence of a different rate of PSA change between these populations., Conclusion: We found that PSA changes over time are similar in UK and US men diagnosed through PSA testing and even in men without PCa. Further development of PSA models to monitor men on active surveillance should be undertaken in order to take advantage of these similarities. We found no evidence that guidelines for using PSA to monitor men cannot be passed between US and European studies., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

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., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: In countries with widespread prostate cancer screening there has been strong stage migration, but little is known about changes within clinical risk categories. Such data are important for the proper interpretation of studies that recruited cases in an earlier era. The purpose of this study was to examine stage migration between and within clinical risk categories., Material and Methods: Using the population-based National Prostate Cancer Register (NPCR) of Sweden, changes in the distribution of prostate-specific antigen (PSA), Gleason score, tumor stage and volume overall between and within clinical risk categories were examined in 120 228 prostate cancer cases diagnosed from 1998 to 2011., Results: Between 1998 and 2011, there was a two-fold increase in the proportion of low-risk prostate cancer (stage T1/T2, Gleason score 2-6 and PSA <10 ng/ml), from 14% to 28%, and more than a two-fold decrease in the proportion of metastatic disease, from 25% to 11%. The proportion of men in the low-risk category with T1c tumors increased two-fold, from 36% to 71%, and PSA levels between 4 and 6 ng/ml increased from 24% to 38%; T2 tumors decreased from 39% to 20% and PSA between 8 and 10 ng/ml decreased from 24% to 15%. The proportion of men with less than 25% of cores involved with cancer increased from 41% to 52% between 2003-2006 and 2007-2011., Conclusions: Low-risk cases today have substantially lower tumor volume and PSA levels than low-risk cases diagnosed in 1998, indicating that outcomes in studies that recruited cases in previous decades represent worst case scenarios.

Purpose: Transrectal ultrasound guided biopsy is the gold standard for detecting prostate cancer but international reports suggest that increasing risks are associated with the procedure. We estimated incidence and risk factors for infection after prostate biopsy as well as 90-day mortality using a nationwide Swedish sample., Material and Methods: We performed a population based study of 51,321 men from PCBaSe between 2006 and 2011. Primary outcome measures were dispensed prescriptions of antibiotics for urinary tract infection and hospitalization with a discharge diagnosis of urinary tract infection. Multivariable logistic regression was used to examine risk factors for infection in men who underwent prostate biopsy., Results: During the 6 months before biopsy the background incidence of urinary tract infection was approximately 2%. Within 30 days after biopsy 6% of the men had a dispensed prescription for urinary tract antibiotics and 1% were hospitalized with infection. The strongest risk factors for an antibiotic prescription were prior infection (OR 1.59, 95% CI 1.45-1.73), high Charlson comorbidity index (OR 1.25, 95% CI 1.11-1.41) and diabetes (OR 1.32, 95% CI 1.17-1.49). Risk of an antibiotic prescription after biopsy decreased from 2006 to 2011 (OR 0.79, 95% CI 0.70-0.90) but the risk of hospital admission increased (OR 2.14, 95% CI 1.58-2.94). No significant increase was observed in 90-day mortality., Conclusions: Severe infections with hospitalization after prostate biopsy are increasing in Sweden. The risk of post-biopsy infection is highest in men with a history of urinary tract infection and those with significant comorbidities., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Aim: Many men diagnosed with localised prostate cancer will eventually be treated with androgen deprivation therapy (ADT). ADT is associated with adverse effects and its timing is controversial. Data on patterns of use are scarce. We describe patterns of ADT use, defined as castration (medical and surgical) or antiandrogen monotherapy initiated after primary treatment, in a population-based cohort., Methods and Materials: Data were extracted from the population-based Prostate Cancer data Base Sweden (PCBaSe). Totally 45,147 men diagnosed between 1997 and 2009 with clinical stage T1-2, N0-NX, M0-MX and prostate specific antigen (PSA)<50ng/ml without primary ADT were included. Outcomes in the period 2006 through 2010 were analysed using a period analysis approach., Results: The cumulative incidence of castration at 10years after diagnosis was 11.6% (95% confidence interval (CI), 11.0-12.2%). The corresponding proportion of antiandrogen monotherapy was 10.8% (95% CI, 10.2-11.4%). Castration was the dominant therapy among men on deferred treatment. The probability of receiving castration rather than antiandrogen monotherapy increased with age. Estimated median durations of castration ranged from 4years in the deferred treatment high-risk group to 17years in the prostatectomy low-risk group. The main limitation was the lack of information on progression to metastatic disease and PSA at the time for initiation of ADT., Conclusion: When initiated early after curative treatment, the duration of castration can be decades. The findings indicate that more accurate tools are necessary to guide which men should be selected for ADT as secondary treatment., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: We investigated hospital readmission frequency during the 90 days after radical prostatectomy and assessed the readmission risk associated with potentially related variables., Materials and Methods: Using the population based, nationwide PCBaSe (Prostate Cancer data Base Sweden) we identified men diagnosed with incident prostate cancer between 2000 and 2011 who underwent radical prostatectomy as primary treatment. We used logistic regression analysis to examine the association of the risk of 90-day postoperative readmission with surgical method, calendar period, tumor risk category, hospital case load and patient characteristics., Results: During 90 postoperative days 2,317 of the 24,122 men (10%) identified were nonelectively readmitted, specifically 10% after retropubic, 9% after robot-assisted and 11% after laparoscopic radical prostatectomy. The range in readmission frequency among hospitals was 0% to 35%. Higher readmission risk was associated with the early calendar period (2009 to 2011 vs 2000 to 2002 OR 0.71, 95% CI 0.61-0.83), greater age (70 or greater vs less than 60 years OR 1.17, 95% CI 1.00-1.36), higher risk category (high vs low OR 1.78, 95% CI 1.57-2.03), high comorbidity (Charlson comorbidity index 3 or greater vs 0 OR 1.77, 95% CI 1.29-2.44) and low hospital surgical volume (150 or greater vs fewer than 30 radical prostatectomies per year OR 0.70, 95% CI 0.60-0.81)., Conclusions: Readmission rates after different radical prostatectomy methods were similar, ranging from 9% to 11%, with wide variation among hospitals. Readmission rates can be used as an indicator of perioperative care quality but potential confounders must be adjusted to avoid bias., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Radical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain., Methods: Between 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy., Results: During 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04)., Conclusions: Extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.).

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

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., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Erectile dysfunction is a common side effect following radical prostatectomy mainly due to damage of the pelvic autonomic nerve fibers (cavernous nerves). Intraoperative electrical stimulation of the cavernous nerves while measuring changes in penile girth has previously been shown to provide the surgeon with feedback of nerve integrity., Aim: To test the feasibility of recording changes in glans penis blood flow by Laser Doppler flowmetry from cavernous nerve stimulation., Methods: Fifteen patients with localized prostate cancer undergoing radical prostatectomy had electrical stimulation of the proximal and distal parts of the neurovascular bundles after prostate removal. The stimulation consisted of 30-40 seconds biphasic constant current (10-30 mA) with 0.5 millisecond pulse duration., Main Outcome Measures: Stimulus induced changes in penile blood flow was recorded from a Laser Doppler probe attached to the glans penis. Changes in penile girth were simultaneously recorded from a mercury-in rubber strain gauge. Erectile function was evaluated three months after surgery., Results: Ten patients had stimulus induced increase in Laser Doppler flow unilaterally (N=7) or bilaterally (N=3). Out of 10 patients, 6 reported some preserved erectile function postoperatively at 3 months follow-up (indicating 6 true and 4 false positives). Three patients had no Doppler response from stimulation and had no postoperative erectile function postoperatively (indicating three true negatives). Two patients were excluded from the study due to bad signal quality in the Laser Doppler signal. In the majority of patients, stimulation produced increase in penile girth sensed by the strain gauge., Conclusion: This preliminary report provides evidence that Laser Doppler Flowmetry is able to detect increased penile blood flow from intraoperative electrical stimulation of the neurovascular bundles. However, further improvement in the recording technique is required. Laser Doppler Flowmetry may also be feasible to confirm autonomic nerve sparing in women undergoing pelvic surgery., (© 2012 International Society for Sexual Medicine.)

Objective: To assess the association between 5α-reductase inhibitor (5-ARI) use in men with lower urinary tract symptoms and prostate cancer risk., Design: Nationwide, population based case-control study for men diagnosed with prostate cancer in 2007-09 within the Prostate Cancer data Base Sweden 2.0., Setting: The National Prostate Cancer Register, National Patient Register, census, and Prescribed Drug Register in Sweden, from which we obtained data on 5-ARI use before date of prostate cancer diagnosis., Participants: 26,735 cases and 133,671 matched controls; five controls per case were randomly selected from matched men in the background population. 7815 men (1499 cases and 6316 controls) had been exposed to 5-ARI. 412 men had been exposed to 5-ARI before the diagnosis of a cancer with Gleason score 8-10., Main Outcome Measures: Risk of prostate cancer calculated as odds ratios and 95% confidence intervals by conditional logistic regression analyses., Results: Risk of prostate cancer overall decreased with an increasing duration of exposure; men on 5-ARI treatment for more than three years had an odds ratio of 0.72 (95% confidence interval 0.59 to 0.89; P<0.001 for trend). The same pattern was seen for cancers with Gleason scores 2-6 and score 7 (both P<0.001 for trend). By contrast, the risk of tumours with Gleason scores 8-10 did not decrease with increasing exposure time to 5-ARI (for 0-1 year of exposure, odds ratio 0.96 (95% confidence interval 0.83 to 1.11); for 1-2 years, 1.07 (0.88 to 1.31); for 2-3 years, 0.96 (0.72 to 1.27); for >3 years, 1.23 (0.90 to 1.68); P=0.46 for trend)., Conclusions: Men treated with 5-ARI for lower urinary tract symptoms had a decreased risk of cancer with Gleason scores 2-7, and showed no evidence of an increased risk of cancer with Gleason scores 8-10 after up to four years' treatment.

Purpose: Risk of suicide is increased among men with prostate cancer. We investigated this association among men with low-risk cancer, usually detected by prostate specific antigen (PSA)-testing., Patients and Methods: Relative risk (RR) of suicide was calculated by use of Poisson regression analysis within the Prostate Cancer data Base Sweden (PCBaSe) 2.0, a nation-wide, population-based database, comparing 105,736 men diagnosed with prostate cancer between 1997-2009 to 528,658 matched prostate cancer-free men., Results: During the first 6 months after diagnosis, there were 38 suicides among men with prostate cancer; incidence rate 0.73 per 1000 person-years (PY) and 30 suicides in the comparison cohort; 0.11 per 1000 PY, corresponding to a RR of suicide of 6.5 (95% confidence interval (CI) 4.0-10). Risk was highest among men with distant metastases, incidence rate 1.25 per 1000 PY, RR 10 (95% CI 5.1-21) but risk was also increased for men with low-risk tumours, incidence rate difference 0.45 per 1000 PY and RR 5.2 (95% CI 2.3-12) and across categories of socioeconomic status and comorbidity. Eighteen months after diagnosis, risk of suicide had decreased to 0.27 per 1000 PY, RR 1.0 (95% CI 0.68-1.5) for low-risk prostate cancer but remained increased among men with metastases, 0.57 per 1000 PY, RR 1.8 (95% CI 1.1-2.9)., Conclusion: Although the increase in absolute risk of suicide was modest, our findings reflect the severe psychological stress that prostate cancer patients may experience after diagnosis. The increased risk of suicide observed in men with prostate cancer, including low-risk, calls for increased awareness., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction: Register-based studies have shown large survival differences among prostate cancer patients in the Nordic countries. The aim of this study was to determine the background of such differences in Denmark, Iceland and Sweden., Material and Methods: Patients with prostate cancer were identified through population-based cancer registers in the three countries. Clinical findings at diagnosis were retrieved from hospital records. In Sweden, clinical information was gathered from regional population-based prostate cancer registers. Country-specific incidence and excess mortality rates were compared, with adjustment for prognostic factors., Results: The relative survival in the cohorts was comparable to that in previous population-based studies. Significant differences in excess mortality rates were found across countries, which diminished or disappeared after adjustment for patient characteristics, i.e. metastatic status, clinical T stage and prostate-specific antigen level. A difference in the proportion of patients with metastatic disease was the main explanation of the differences in survival among countries, while the incidence rates of metastatic cancer were similar., Discussion: Register-based studies of the relative survival of prostate cancer patients are influenced by national differences in clinical presentation at diagnosis. Differences in the proportion of patients with metastatic spread explained most of the difference in relative survival among patients in Denmark, Iceland and Sweden. Future country comparisons of relative survival should include adjustment for differences in patient characteristics, such as stage, prostate-specific antigen level and screening intensity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Prostate cancer (PCa) and surgery are both associated with increased risk of thromboembolic diseases (TED)., Objective: We assessed risk of TED among men undergoing different types of urologic surgery., Design, Setting, and Participants: Using the Prostate Cancer Database Sweden (PCBaSe) Sweden, we identified all men (n=45 065) undergoing pelvic lymph node dissection (PLND), radical prostatectomy (RP) with or without PLND, orchiectomy due to PCa, or a transurethral resection of the prostate (TURP). We identified a comparison cohort from the population., Outcome Measurements and Statistical Analysis: Main outcomes were deep venous thrombosis (DVT) and pulmonary embolism (PE) as primary diagnoses in the National Patient Register or Cause of Death Register (2002-2010). We calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable Cox proportional hazards models., Results and Limitations: All surgical procedures were associated with increased risk of TED; laparoscopic and open RP with a PLND were the most strongly associated with TED (HR for PE: 8.1 [95% CI, 2.9-23.0] and 7.8 [95% CI, 4.9-13], respectively). For surgery including a PLND, the risk increased during the second half of the first postoperative month. The HR for PE after TURP in men with PCa was 3.0 (95% CI, 1.8-5.1). Patients with a history of TED had a strongly increased risk of TED (HR for DVT: 4.5; 95% CI, 2.6-8.0). A limitation is lack of information on TED prophylaxis, but its use was standardized during the study period for RP and PLND. Other limitations are lack of information on extent of PLND and lifestyle factors., Conclusions: Surgeries for PCa, including TURP, are associated with hospitalization for TED. Patients with a history of TED and patients undergoing a PLND were at highest risk. The largest risk was observed from days 14 to 28 postoperatively. Thus, our results suggest that prophylactic measures may be beneficial during the first 4 wk in these patients., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

In the Scandinavian Prostate Cancer Group Trial Number 4 (SPCG-4), 347 men were randomly assigned to radical prostatectomy and 348 to watchful waiting. In the most recent analysis (median follow-up time = 12.8 years), the cumulative mortality curves had been stable over the follow-up. At 15 years, the absolute risk reduction of dying from prostate cancer was 6.1% following randomization to radical prostatectomy, compared with watchful waiting. Hence, 17 need to be randomized to operation to avert one death. Data on self-reported symptoms, stress from symptoms, and quality of life were collected at 4 and 12.2 years of median follow-up. These questionnaire studies show an intricate pattern of symptoms evolving after surgery, hormonal treatments, signs of tumor progression, and also from natural aging. This article discusses some of the main findings of the SPCG-4 study.

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., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Although there is randomized evidence that radical prostatectomy improves survival, there are few data on how benefit varies by baseline risk., Objective: We aimed to create a statistical model to calculate the decrease in risk of death associated with surgery for an individual patient, using stage, grade, prostate-specific antigen, and age as predictors., Design, Setting, and Participants: A total of 695 men with T1 or T2 prostate cancer participated in the Scandinavian Prostate Cancer Group 4 trial (SPCG-4)., Intervention: Patients in SPCG-4 were randomized to radical prostatectomy or conservative management., Outcome Measurements and Statistical Analysis: Competing risk models were created separately for the radical prostatectomy and the watchful waiting group, with the difference between model predictions constituting the estimated benefit for an individual patient., Results and Limitations: Individualized predictions of surgery benefit varied widely depending on age and tumor characteristics. At 65 yr of age, the absolute 10-yr risk reduction in prostate cancer mortality attributable to radical prostatectomy ranged from 4.5% to 17.2% for low- versus high-risk patients. Little expected benefit was associated with surgery much beyond age 70. Only about a quarter of men had an individualized benefit within even 50% of the mean. A limitation is that estimates from SPCG-4 have to be applied cautiously to contemporary patients., Conclusions: Our model suggests that it is hard to justify surgery in patients with Gleason 6, T1 disease or in those patients much above 70 yr of age. Conversely, surgery seems unequivocally of benefit for patients who have Gleason 8, or Gleason 7, stage T2. For patients with Gleason 6 T2 and Gleason 7 T1, treatment is more of a judgment call, depending on patient preference and other clinical findings, such as the number of positive biopsy cores and comorbidities., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Prostate cancer patients have an increased risk of fractures as a consequence of skeletal metastases and osteoporosis induced by endocrine treatment. Data on incidence of fractures and risks in subgroups of men with prostate cancer are sparse. Our aim with this study is to report the risk of fractures among men with prostate cancer in a nationwide population-based study., Patients and Methods: We identified 76,600 Swedish men diagnosed with prostate cancer 1997-2006 in the Prostate Cancer Data Base (PCBaSe) Sweden and compared the occurrence of fractures requiring hospitalisation with the Swedish male population., Results: Only men treated with gonadotropin releasing-hormone (GnRH) agonists or orchiectomy had increased incidence and increased relative risk of fractures requiring hospitalisation. Men treated with GnRH agonists had 9.8 and 6.3/1000 person-years higher incidence of any fracture and hip fracture requiring hospitalisation than the general population. The corresponding increases in incidence for men treated with orchiectomy were 16 and 12/1000 person-years, respectively. Men treated with orchiectomy, GnRH agonists, and antiandrogen monotherapy, had SIR for hip fracture of 2.0 (95% Confidence Interval 1.8-2.2), 1.6 (95% CI 1.5-1.8) and 0.9 (95% CI 0.7-1.1), respectively. Men treated with a curative intent (radical prostatectomy or radiotherapy) or managed with surveillance had no increased risk of fractures. Older men had the highest incidence of fractures while younger men had the highest relative risk., Conclusion: Prostate cancer patients treated with GnRH agonists or orchiectomy have significantly increased risk of fractures requiring hospitalisation while patients treated with antiandrogen monotherapy had no increase in such fractures. In absolute terms the excess risk in men treated with GnRH agonists corresponded to almost 10 extra fractures leading to hospitalisation per 1000 patient-years. Effects on bone density should be considered for men on long-term endocrine treatment. Unwarranted use of orchiectomy and GnRH agonists should be avoided., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Aim: To explore whether the self-reported psychological distress among men with prostate cancer was to the extent that it required psychiatric treatment., Methods: PCBaSe Sweden, a merged database based on the National Prostate Cancer Register including 97% of all prostate cancers registered as well as age-matched controls. We calculated relative risks and 95% confidence intervals to compare risks of psychiatric treatment due to depression, anxiety, and post-traumatic stress disorder controlling for age and socio-economic factors. We used odds ratios to compare use or no use of antidepressants., Findings: In total 72,613 men with prostate cancer and 217,839 men without prostate cancer were included for analyses. Psychiatric hospitalisation due to depression, anxiety and post-traumatic stress disorder were significantly increased (RR 1.29, (95% CI 1.14-1.45), RR 1.42 (95% CI 1.12-1.80) and RR 1.61 (95% CI 1.16-2.24), respectively). However, hospitalisations due to anxiety were only increased in men with more advanced tumours RR 2.28 (95% CI 1.45-3.57). The use of antidepressants was increased for all men with prostate cancer RR 1.65 (95% CI 1.54-1.77) and treatment strategies RR 1.93 (95% CI 1.75-2.13)., Interpretation: Men diagnosed with prostate cancer had increased risk of psychiatric treatment for depression, post-traumatic stress disorder and use of antidepressants regardless of risk group and treatment strategy compared to age-matched controls, whilst more advanced prostate cancer was associated with severe anxiety disorders., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years., Methods: All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint., Findings: 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7-17) and a median age of 77·0 years (range 61-88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07-1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life., Interpretation: For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information., Funding: US National Institutes of Health; Swedish Cancer Society; Foundation in Memory of Johanna Hagstrand and Sigfrid Linnér., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results., Methods: From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model., Results: During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4)., Conclusions: Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment. (Funded by the Swedish Cancer Society and the National Institutes of Health.).