Defining Intermediate Risk Prostate Cancer Suitable for Active Surveillance.

PURPOSE: Active surveillance of intermediate risk prostate cancer is controversial. Many active surveillance programs are limited to men with Grade Group 1 (Gleason 6) disease and prostate specific antigen less than 10 ng/ml. However, recent guidelines state that active surveillance can be considered in cases of limited Grade Group 2 (Gleason 3 + 4) despite limited data on outcomes. We compared prostatectomy outcomes between prostate cancer subgroups of intermediate risk vs low risk. MATERIALS AND METHODS: We performed an observational study in the National Prostate Cancer Register of Sweden, which includes 98% of prostate cancer cases nationwide. From 2009 to 2012 radical prostatectomy was performed in 5,087 men with low risk prostate cancer (Grade Group 1, prostate specific antigen less than 10 ng/ml and cT2 or less) and intermediate risk prostate cancer (Grade Group 2, prostate specific antigen 10 to 20 ng/ml or T2). We compared upgrading and up staging between the groups based on the CAPRA (Cancer of the Prostate Risk Assessment) scores and published active surveillance criteria. Results were validated in an independent data set of cases diagnosed from 2013 to 2016. RESULTS: Men with Grade Group 1, prostate specific antigen 10 to 15 ng/ml and prostate specific antigen density less than 0.15 ng/ml/cm did not significantly differ in upgrading or adverse pathology findings compared to men with low risk prostate cancer. Prostate specific antigen greater than 15 ng/ml or Grade Group 2 was associated with a significantly greater risk of aggressive prostate cancer. Men with low risk CAPRA scores (0 to 2) and Grade Group 2 disease were at almost threefold increased risk of upgrading and twofold increased risk of adverse pathology compared to men with low risk CAPRA, Grade Group 1 disease. CONCLUSIONS: Expanding the prostate specific antigen threshold to 15 ng/ml for Grade Group 1 prostate cancer would allow more men to elect active surveillance. This is unlikely to compromise outcomes, particularly if prostate specific antigen density is low. In contrast, caution should be exercised in offering active surveillance to men with prostate specific antigen greater than 15 ng/ml or Grade Group 2 prostate cancer.

Work-up and treatment of prostate cancer before and after publication of the first national guidelines on prostate cancer care in Sweden.

BACKGROUND AND OBJECTIVES: In 2007, the Swedish National Board of Health and Welfare published the first Swedish guidelines on prostate cancer (PCa) to improve care and decrease geographical and social inequalities. The aim of this analysis was to assess how these guidelines affected PCa care. MATERIALS AND METHODS: Work-up and treatment for men diagnosed with PCa between 1998 and 2014 were assessed by use of data in the Prostate Cancer data Base Sweden (PCBaSe) with information from the National Prostate Cancer Register (NPCR) and other healthcare registries and demographic databases. RESULTS: Overall, there were modest improvements in the performance for 14 selected quality indicators, with some notable exceptions. There was a strong increase in the use of active surveillance for very low-risk PCa, up from 56% in 2009 to 92% in 2014, and use of bone imaging for high-risk PCa up from 50% in 2008 to 77% in 2014. There were large differences in work-up and treatment of PCa between healthcare providers with modest decreases over time. The differences between counties were larger than differences according to socioeconomic status with one exception: use of curative treatment for high-risk PCa was more common in men with high income, highest versus lowest tertile, OR 2.74 (95% CI, 1.85-4.06). CONCLUSION: The modest improvements in PCa care after the publications of national guidelines indicate that if these are to make an impact on care, feedback to each point of care on their performance as well as local quality improvement programs implementing the guidelines are needed.

Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population-based setting: a report from the Swedish MDS register.

The myelodysplastic syndromes (MDS) have highly variable outcomes and prognostic scoring systems are important tools for risk assessment and to guide therapeutic decisions. However, few population-based studies have compared the value of the different scoring systems. With data from the nationwide Swedish population-based MDS register we validated the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) and the World Health Organization (WHO) Classification-based Prognostic Scoring System (WPSS). We also present population-based data on incidence, clinical characteristics including detailed cytogenetics and outcome from the register. The study encompassed 1329 patients reported to the register between 2009 and 2013, 14% of these had therapy-related MDS (t-MDS). Based on the MDS register, the yearly crude incidence of MDS in Sweden was 2·9 per 100 000 inhabitants. IPSS-R had a significantly better prognostic power than IPSS (P < 0·001). There was a trend for better prognostic power of IPSS-R compared to WPSS (P = 0·05) and for WPSS compared to IPSS (P = 0·07). IPSS-R was superior to both IPSS and WPSS for patients aged ≤70 years. Patients with t-MDS had a worse outcome compared to de novo MDS (d-MDS), however, the validity of the prognostic scoring systems was comparable for d-MDS and t-MDS. In conclusion, population-based studies are important to validate prognostic scores in a 'real-world' setting. In our nationwide cohort, the IPSS-R showed the best predictive power.

Nationwide population-based study on the use of novel antiandrogens in men with prostate cancer in Sweden.

OBJECTIVES: The aim of this study was to examine the use of abiraterone and enzalutamide, two oral novel antiandrogens (NOVAs), in men with prostate cancer (PCa) in Sweden. MATERIALS AND METHODS: This cross-sectional study investigated filled prescriptions for NOVAs recorded in the Swedish Prescribed Drug Register between July 2015 and April 2016. Associations between age, comorbidity, educational level, marital status and county of residence and filled prescriptions were analyzed in the National Prostate Cancer Register (NPCR) and other health population-based registers, using multivariable logistic regression. RESULTS: Of 91,209 men, 1650 (2%) had at least one prescription filled for NOVAs, of whom 1350 (82%) had high-risk or metastatic PCa at diagnosis.. Of 1914 men with M1 disease and a high probability of castration-resistant prostate cancer (CRPC), 22% had a prescription for NOVAs at a median 3 years after the date of diagnosis. At multivariable logistic regression analysis,, the likelihood of NOVA use was lower in older men [age >80 vs <70 years: odds ratio (OR) 0.23, 95% confidence interval (CI) 0.15-0.35] and in men with lower educational level (high vs low education: OR 1.64, 95% CI 1.23-2.20). There was up to a five-fold difference in the use of NOVAs between county councils. CONCLUSIONS: Less than one-third of potentially eligible men with CRPC received NOVAs in 2015-2016. There were large differences in use according to age and region of residence, indicating that efforts are needed to improve equal access to novel cancer drugs.

Temporal trends in incidence and outcome of hydatidiform mole: a retrospective cohort study.

BACKGROUND: Reported incidence rates of hydatidiform mole (HM) show wide geographic and temporal variations, making reliable international comparisons difficult. The aim of the current study was to examine temporal trends in the incidence of HM and post-molar gestational trophoblastic neoplasia (GTN) in Stockholm County. MATERIAL AND METHODS: Data of all women with a diagnosis of HM in Stockholm County 1991-2010 was collected. The incidence of HM was assessed both in relation to number of births and viable conceptions (births and pregnancy terminations). The risk of post-molar GTN was analysed for all HM, as well as for the subtypes complete (CHM) and partial hydatidiform mole (PHM). Temporal trends were analysed by stratifying the study period into five-year intervals. RESULTS: The overall incidence rate of HM was 2.08/1000 deliveries and 1.48/1000 viable conceptions. A significant temporal increase in the incidence rate of HM, as well as in the total number and proportion of PHM, was seen. Among 956 women with HM, 77 (8%) progressed into post-molar GTN. There was evidence of a slight, but non-significant increase in the risk of malignancy in the two last five-year periods under study. CONCLUSIONS: We found evidence of a significant temporal increase in the incidence rate of HM, which could not fully be explained by an increase in maternal age over time. Changes in diagnostic methods probably contributed to the increased incidence rate of PHM. The risk of post-molar GTN remained constant over time.

Nationwide, population-based study of post radical prostatectomy urinary incontinence correction surgery.

OBJECTIVES: To assess the use of post radical prostatectomy (RP) urinary incontinence (PPI) surgery and to investigate factors related to its use. METHODS: Cohort study in Prostate Cancer database Sweden (PCBaSe) of men who underwent primary RP between 1998 and 2012. PPI correction procedures were identified in the Patient Registry. Hazard ratios (HR) and 95% confidence intervals (CIs) of PPI surgeries were estimated. RESULTS: Seven hundred eighty-two out of 26 280 (3%) men underwent PPI surgery at a median time of 3 years after RP. There was an eightfold increase in the absolute number of PPI surgeries during 2000-2014 and a threefold increase in the number per 1000 RPs performed. Factors associated with high use PPI surgery were age >70, HR 1.96 (1.54-2.50), and high hospital RP volume (>100 RPs/year), HR 0.81 (0.66-0.99). There was a 10-fold difference in use of PPI surgery per 1000 RPs between the county with the highest versus lowest use. In a subgroup of men with Patient-Reported Outcome Measures (PROM); severe PPI was reported by 7% of men and 24% of them underwent PPI surgery. CONCLUSIONS: Three percent of all men received PPI surgery, with a 10-fold variation among health care providers. Only a quarter of men with severe PPI underwent PPI surgery, suggesting that PPI surgery remains underutilized.

Meta-Analysis of the Association Between Phosphodiesterase Inhibitors (PDE5Is) and Risk of Melanoma.

The US Food and Drug Administration recently announced the need to evaluate the association between PDE5is and melanoma. We performed a meta-analysis on the association between PDE5i and melanoma using random effects models and examined whether it met Hill's criteria for causality. A systematic search of Medline, EMBASE, and the Cochrane Library from 1998 to 2016 identified three case-control studies and two cohort studies, including a total of 866 049 men, of whom 41 874 were diagnosed with melanoma. We found a summary estimate indicating an increased risk of melanoma in PDE5i users (relative risk = 1.11, 95% confidence interval = 1.02 to 1.22). However, the association was only statistically significant among men with low PDE5i exposure (not high exposure) and with low-stage melanoma (not high stage), indicating a lack of dose response and biological gradient. PDE5i use was also associated with basal cell cancer, suggesting a lack of specificity and likely confounding by ultraviolet exposure. Thus, although this meta-analysis found a statistically significant association between PDE5i and melanoma, it did not satisfy Hill's criteria for causality.

Long-term adverse effects after retropubic and robot-assisted radical prostatectomy. Nationwide, population-based study.

BACKGROUND AND OBJECTIVES: Surgery for prostate cancer is associated with adverse effects. We studied long-term risk of adverse effects after retropubic (RRP) and robot-assisted radical prostatectomy (RARP). METHODS: In the National Prostate Cancer Register of Sweden, men who had undergone radical prostatectomy (RP) between 2004 and 2014 were identified. Diagnoses and procedures indicating adverse postoperative effects were retrieved from the National Patient Register. Relative risk (RR) of adverse effects after RARP versus RRP was calculated in multivariable analyses adjusting for year of surgery, hospital surgical volume, T stage, Gleason grade, PSA level at diagnosis, patient age, comorbidity, and educational level. RESULTS: A total of 11 212 men underwent RRP and 8500 RARP. Risk of anastomotic stricture was lower after RARP than RRP, RR for diagnoses 0.51 (95%CI = 0.42-0.63) and RR for procedures 0.46 (95%CI = 0.38-0.55). Risk of inguinal hernia was similar after RARP and RRP but risk of incisional hernia was higher after RARP, RR for diagnoses 1.48 (95%CI = 1.01-2.16), and RR for procedures 1.52 (95%CI = 1.02-2.26). CONCLUSIONS: The postoperative risk profile for RARP and RRP was quite similar. However, risk of anastomotic stricture was lower and risk of incisional hernia higher after RARP.

A combinatorial screen of the CLOUD uncovers a synergy targeting the androgen receptor.

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

Testosterone Replacement Therapy and Risk of Favorable and Aggressive Prostate Cancer.

Purpose The association between exposure to testosterone replacement therapy (TRT) and prostate cancer risk is controversial. The objective was to examine this association through nationwide, population-based registry data. Methods We performed a nested case-control study in the National Prostate Cancer Register of Sweden, which includes all 38,570 prostate cancer cases diagnosed from 2009 to 2012, and 192,838 age-matched men free of prostate cancer. Multivariable conditional logistic regression was used to examine associations between TRT and risk of prostate cancer (overall, favorable, and aggressive). Results Two hundred eighty-four patients with prostate cancer (1%) and 1,378 control cases (1%) filled prescriptions for TRT. In multivariable analysis, no association was found between TRT and overall prostate cancer risk (odds ratio [OR], 1.03; 95% CI, 0.90 to 1.17). However, patients who received TRT had more favorable-risk prostate cancer (OR, 1.35; 95% CI, 1.16 to 1.56) and a lower risk of aggressive prostate cancer (OR, 0.50; 95% CI, 0.37 to 0.67). The increase in favorable-risk prostate cancer was already observed within the first year of TRT (OR, 1.61; 95% CI, 1.10 to 2.34), whereas the lower risk of aggressive disease was observed after > 1 year of TRT (OR, 0.44; 95% CI, 0.32 to 0.61). After adjusting for previous biopsy findings as an indicator of diagnostic activity, TRT remained significantly associated with more favorable-risk prostate cancer and lower risk of aggressive prostate cancer. Conclusion The early increase in favorable-risk prostate cancer among patients who received TRT suggests a detection bias, whereas the decrease in risk of aggressive prostate cancer is a novel finding that warrants further investigation.

Socioeconomic factors and penile cancer risk and mortality; a population-based study.

OBJECTIVE: To investigate possible associations between socioeconomic status (SES) and penile cancer risk, stage at diagnosis, and mortality. PATIENTS/SUBJECTS AND METHODS: A population-based register study including men in Sweden diagnosed with penile cancer between 2000 and 2012 (1676 men) and randomly chosen controls (9872 men). Data were retrieved from the National Penile Cancer Register (NPECR) and several other population-based healthcare and sociodemographic registers. Educational level, disposable income, marital status, and number of individuals in the household, were assessed as indicators of SES. The risk of penile cancer and penile cancer death in relation to SES were estimated using logistic regression and proportional hazards models, respectively. Cumulative cause-specific mortality (CSM) estimates by SES were calculated using the Kaplan-Meier method. RESULTS: A low educational level and low disposable income were associated with an increased risk of invasive penile cancer. Furthermore, low educational level was associated with more advanced primary tumour stage. Divorced and never married men had a generally increased risk of penile cancer and were diagnosed with more advanced primary tumour stages. However, neither educational level nor marital status was associated with lymph node or distant metastases. Also, men in single-person households had an increased risk of both non-invasive and invasive disease. In men with invasive penile cancer, there were no significant associations of indicators of SES and CSM. CONCLUSIONS: Low educational level, low disposable income, being divorced or never married, and living in a single-person household, all increase the risk of advanced stage penile cancer, but not lymph node or distant metastases. The assessed indicators of SES did not influence penile CSM. In conclusion, our findings indicates that SES influences the risk and stage of penile cancer, but not survival.

Uptake of Active Surveillance for Very-Low-Risk Prostate Cancer in Sweden.

IMPORTANCE: Active surveillance is an important option to reduce prostate cancer overtreatment, but it remains underutilized in many countries. Models from the United States show that greater use of active surveillance is important for prostate cancer screening to be cost-effective. OBJECTIVES: To perform an up-to-date, nationwide, population-based study on use of active surveillance for localized prostate cancer in Sweden. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study in the National Prostate Cancer Register (NPCR) of Sweden from 2009 through 2014. The NPCR has data on 98% of prostate cancers diagnosed in Sweden and has comprehensive linkages to other nationwide databases. Overall, 32 518 men with a median age of 67 years were diagnosed with favorable-risk prostate cancer, including 4693, 15 403, and 17 115 men with very-low-risk (subset of the low-risk group) (clinical stage, T1c; Gleason score, ≤6; prostate-specific antigen [PSA], <10 ng/mL; PSA density <0.15 ng/mL/cm3; and <8-mm total cancer length in ≤4 positive biopsy cores), low-risk (including all men in the very-low-risk group) (T1-T2; Gleason score, ≤6; and PSA, <10 ng/mL), and intermediate-risk disease (T1-T2 with Gleason score, 7 and/or PSA, 10-20 ng/mL). EXPOSURES: Diagnosis with favorable-risk prostate cancer. MAIN OUTCOMES AND MEASURES: Utilization of active surveillance. RESULTS: The use of active surveillance increased in men of all ages from 57% (380 of 665) to 91% (939 of 1027) for very-low-risk prostate cancer and from 40% (1159 of 2895) to 74% (1951 of 2644) for low-risk prostate cancer, with the strongest increase occurring from 2011 onward. Among men aged 50 to 59 years, 88% (211 of 240) with very-low-risk and 68% (351 of 518) with low-risk disease chose active surveillance in 2014. Use of active surveillance for intermediate-risk disease remained lower, 19% (561 of 3030) in 2014. CONCLUSIONS AND RELEVANCE: Active surveillance has become the dominant management for low-risk prostate cancer among men in Sweden, with the highest rates yet reported and almost complete uptake for very-low-risk cancer. These data should serve as a benchmark to compare the use of active surveillance for favorable-risk disease around the world.

Prognostic implications of 2005 Gleason grade modification. Population-based study of biochemical recurrence following radical prostatectomy.

OBJECTIVE: To assess the impact of the 2005 modification of the Gleason classification on risk of biochemical recurrence (BCR) after radical prostatectomy (RP). PATIENTS AND METHODS: In the Prostate Cancer data Base Sweden (PCBaSe), 2,574 men assessed with the original Gleason classification and 1,890 men assessed with the modified Gleason classification, diagnosed between 2003 and 2007, underwent primary RP. Histopathology was reported according to the Gleason Grading Groups (GGG): GGG1 = Gleason score (GS) 6, GGG2 = GS 7(3 + 4), GGG3 = GS 7(4 + 3), GGG4 = GS 8 and GGG5 = GS 9-10. Cumulative incidence and multivariable Cox proportional hazards regression models were used to assess difference in BCR. RESULTS: The cumulative incidence of BCR was lower using the modified compared to the original classification: GGG2 (16% vs. 23%), GGG3 (21% vs. 35%) and GGG4 (18% vs. 34%), respectively. Risk of BCR was lower for modified versus original classification, GGG2 Hazard ratio (HR) 0.66, (95%CI 0.49-0.88), GGG3 HR 0.57 (95%CI 0.38-0.88) and GGG4 HR 0.53 (95%CI 0.29-0.94). CONCLUSION: Due to grade migration following the 2005 Gleason modification, outcome after RP are more favourable. Consequently, outcomes from historical studies cannot directly be applied to a contemporary setting. J. Surg. Oncol. 2016;114:664-670. © 2016 Wiley Periodicals, Inc.

Long-term adverse effects after curative radiotherapy and radical prostatectomy: population-based nationwide register study.

OBJECTIVE: The aim of this study was to assess the risk of serious adverse effects after radiotherapy (RT) with curative intention and radical prostatectomy (RP). MATERIALS AND METHODS: Men who were diagnosed with prostate cancer between 1997 and 2012 and underwent curative treatment were selected from the Prostate Cancer data Base Sweden. For each included man, five prostate cancer-free controls, matched for birth year and county of residency, were randomly selected. In total, 12,534 men underwent RT, 24,886 underwent RP and 186,624 were controls. Adverse effects were defined according to surgical and diagnostic codes in the National Patient Registry. The relative risk (RR) of adverse effects up to 12 years after treatment was compared to controls and the risk was subsequently compared between RT and RP in multivariable analyses. RESULTS: Men with intermediate- and localized high-risk cancer who underwent curative treatment had an increased risk of adverse effects during the full study period compared to controls: the RR of undergoing a procedures after RT was 2.64 [95% confidence interval (CI) 2.56-2.73] and after RP 2.05 (95% CI 2.00-2.10). The risk remained elevated 10-12 years after treatment. For all risk categories of prostate cancer, the risk of surgical procedures for urinary incontinence was higher after RP (RR 23.64, 95% CI 11.71-47.74), whereas risk of other procedures on the lower urinary tract and gastrointestinal tract or abdominal wall was higher after RT (RR 1.67, 95% CI 1.44-1.94, and RR 1.86, 95% CI 1.70-2.02, respectively). CONCLUSION: The risk of serious adverse effects after curative treatment for prostate cancer remained significantly elevated up to 12 years after treatment.

Immediate versus delayed prostatectomy: Nationwide population-based study (.).

OBJECTIVE: The aim of this study was to compare the outcome of immediate versus delayed radical prostatectomy (RP) in men with low-grade prostate cancer. MATERIALS AND METHODS: The study included a nationwide population-based cohort in the National Prostate Cancer Register of Sweden, of 7608 men with clinically localized, biopsy Gleason score 6 prostate cancer who underwent immediate or delayed RP in 1997-2007. Multivariable models compared RP pathology, use of salvage radiotherapy and prostate cancer mortality based on timing of RP (< 1, 1-2 or >2 years after diagnosis). Median follow-up was 8.1 years. RESULTS: Men undergoing RP more than 2 years after diagnosis had a higher risk of Gleason upgrading [odds ratio 2.93, 95% confidence interval (CI) 2.34-3.68] and an increased risk of salvage radiotherapy [hazard ratio (HR) 1.90, 95% CI 1.41-2.55], but no significant increase in prostate cancer-specific mortality (HR 1.85, 95% CI 0.57-5.99). In competing risk analysis, 7 year prostate cancer-specific cumulative mortality was similar, at less than 1%, for immediate RP and active surveillance regardless of later intervention. Limitations of this study include the lack of data on follow-up biopsies and the limited follow-up time. CONCLUSION: Men undergoing RP more than 2 years after diagnosis had more adverse pathological features and second line therapy, highlighting the trade-off in deferring immediate curative therapy. However, men with delayed RP constitute a minority with higher risk cancer among the much larger group of low-risk men initially surveilled, and the overall risk of prostate cancer mortality at 7 years was similarly low with immediate RP or active surveillance.

Small bowel obstruction and abdominal pain after robotic versus open radical prostatectomy.

Objective The aim of this study was to examine whether intraperitoneal robot-assisted surgery leads to small bowel obstruction (SBO), possibly caused by the formation of intra-abdominal adhesions. Materials and methods In total, 7256 men treated by intraperitoneal robot-assisted radical prostatectomy (RARP) and 9787 men treated by retropubic radical prostatectomy (RRP) in 2005-2012 were identified in the Prostate Cancer data Base Sweden (PCBaSe). Multivariable Cox proportional hazards models were used to calculate the risk of readmission for SBO, SBO-related surgery and admissions due to abdominal pain up to 5 years postoperatively. Results During the first postoperative year, the risk of readmission for SBO was higher after RARP than after RRP [hazard ratio (HR) 1.92, 95% confidence interval (CI) 1.14-3.25] but after 5 years there was no significant difference (HR 1.28, 95% CI 0.86-1.91), and there was no difference in the risk of SBO surgery during any period. The risk of admission for abdominal pain was significantly increased after RARP during the first year (HR 2.24, 95% CI 1.50-3.33) but not after 5 years (HR 1.23, 95% CI 0.92-1.63). Conclusion Intraperitoneal RARP had an increased risk of SBO and abdominal pain in the short term during the first year, but not in the long term, compared to RRP.

Phosphodiesterase Type 5 Inhibitor Use and Disease Recurrence After Prostate Cancer Treatment.

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.

Postoperative mortality 90 days after robot-assisted laparoscopic prostatectomy and retropubic radical prostatectomy: a nationwide population-based study.

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

Causes of death in men with localized prostate cancer: a nationwide, population-based study.

OBJECTIVE: To detail the distribution of causes of death from localized prostate cancer (PCa). PATIENTS AND METHODS: The database PCBase Sweden links the Swedish National Prostate Cancer Register with other nationwide population-based healthcare registers. We selected all 57 187 men diagnosed with localized PCa between 1997 and 2009 and their 114 374 PCa-free control subjects, matched according to age and county of residence. Mortality was calculated using competing risk regression analyses, taking into account PCa risk category, age and Charlson comorbidity index (CCI). RESULTS: In men with low-risk PCa, all-cause mortality was lower compared with that in corresponding PCa-free men: 10-year all-cause mortality was 18% for men diagnosed at age 70 years, with a CCI score of 0, and 21% among corresponding control subjects. Of these cases, 31% died from cardiovascular disease (CVD) compared with 37% of the corresponding control subjects. For men with low-risk PCa, 10-year PCa-mortality was 0.4, 1 and 3% when diagnosed at age 50, 60 and 70 years, respectively. PCa was the third most common cause of death (18%), after CVD (31%) and other cancers (30%). By contrast, PCa was the most common cause of death in men with intermediate- and high-risk localized PCa. CONCLUSIONS: Men with low-risk PCa had lower all-cause mortality than PCa-free men because of lower CVD mortality, driven by early detection selection; however, for men with intermediate- or high-risk disease, the rate of PCa death was substantial, irrespective of CCI score, and this was even more pronounced for those diagnosed at age 50 or 60 years.

Risk of malignant melanoma in men with prostate cancer: Nationwide, population-based cohort study.

An increased risk of malignant melanoma has been observed in men with prostate cancer. To assess potential shared risk factors and confounding factors, we analysed risk of melanoma in men with prostate cancer including information on tumor characteristics and demographics including socioeconomic status. In The Prostate Cancer data Base Sweden, risk of melanoma was assessed in a cohort of men with prostate cancer and in a comparison cohort of prostate-cancer free men. Data on prostate cancer risk category, melanoma stage, basal cell carcinoma, location of residency, and socioeconomic status were obtained from nationwide registers. Melanoma was diagnosed in 830/108,145 (0.78%) men with prostate cancer and in 3,699/556,792 (0.66%) prostate cancer-free men. In multivariable Cox regression models, men with prostate cancer had a significantly increased risk of melanoma (HR 1.18, 95% CI 1.09-1.27), and so had married men, men with high education and income, and men residing in southern Sweden. The strongest associations were observed for stage 0 melanoma in men with low-risk prostate cancer (HR 1.45, 1.14-1.86), high education (HR 1.87, 1.60-2.18) and top income (HR 1.61, 1.34-1.93), respectively, whereas there was no association between these factors and late-stage melanoma. Men with prostate cancer also had an increased risk of basal cell carcinoma (HR 1.18, 1.15-1.22). In conclusion, men with low-risk prostate cancer, high education, high income and residency in southern Sweden had an increased risk of early-stage melanoma.