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Background: Conclusive evidence of superiority in oncological outcome for robot-assisted laparoscopic prostatectomy (RALP) over retropubic radical prostatectomy (RRP) is lacking., Objective: To compare RALP and RRP regarding recurrent disease and to report the mortality rate 6 yr after surgery., Design Setting and Participants: A total of 4003 men with localized prostate cancer were enrolled between 2008 and 2011 in Laparoscopic Prostatectomy Robot Open (LAPPRO)- a prospective, controlled, nonrandomized trial performed at 14 Swedish centers., Outcome Measurements and Statistical Analysis: Data were collected at visits and by patient questionnaires at 3, 12, and 24 mo, and through a structured telephone interview at 6 yr. Cause of death was retrieved from the National Cause of Death Register in Sweden. The modified Poisson regression approach was used for analyses., Results and Limitations: After adjustment for patient-, tumor-, and surgeon-related confounders, no statistically significant difference was observed between RALP and RRP in biochemical recurrence rate (14 vs 16%, relative risk [RR] 0.77, 95% confidence interval [CI] 0.56-1.06) or in not cured endpoint (22% vs 23%, RR 0.82, 95% CI 0.6-1.11). Stratified by D'Amico risk group, a significant benefit for RALP existed for recurrent disease in high-risk patients (RR 0.47, 95% CI 0.26-0.86, p  = 0.02). All-cause mortality was 3% ( n  = 96). Prostate cancer-specific mortality was 0.6% ( n  = 21) overall, 0.3% ( n  = 8) after RALP, and 1.5% ( n  = 13) after RRP. The nonrandomized design is a limitation., Conclusions: No significant difference was observed for cancer recurrence rate between RALP and RRP 6 yr after surgery. However, in a subgroup analysis, we found a significant benefit for RALP regarding recurrence rate in the high-risk group. Larger studies with longer follow-up are needed to make a firm conclusion and to evaluate a possible survival benefit., Patient Summary: In general, the oncological outcome is comparable between robotic and open radical prostatectomy 6 yr after surgery. For high-risk patients, our findings indicate that there is an advantage for robotics, but further studies with longer follow-up time is needed to make a firm conclusion., (© 2020 Published by Elsevier B.V. on behalf of European Association of Urology.)

Purpose: We investigated whether men with biopsy verified, low grade cancer and a family history of lethal or advanced prostate cancer are at particularly high risk for harboring undetected high grade disease., Materials and Methods: Upgrading and up staging of prostate cancer are common after prostatectomy. In a nationwide population based cohort we identified 6,854 men with low risk prostate cancer who underwent radical prostatectomy. Among these men 1,739 (25%) had a history of prostate cancer in a first-degree relative and 289 (4%) had a first-degree relative with lethal or advanced prostate cancer., Results: Compared to men with no familial occurrence of prostate cancer, the odds ratio for the risk of up staging among men with a familial occurrence of high risk or lethal prostate cancer was 1.06 (95% CI 0.76-1.47). The corresponding odds ratio for upgrading was 1.17 (0.91-1.50)., Conclusions: We found no association between family history of prostate cancer and up staging or upgrading after radical prostatectomy.

Background: This study investigated prostate cancer (PC)-specific survival and overall survival (OS) in a population-based castration-resistant PC (CRPC) cohort. Methods: Data from Stockholm Prostate-Specific Antigen (PSA) and Biopsy Register patients with increasing PSA despite gonadotropin-releasing hormone treatment or surgical castration ( n  = 1,712) included PSA values and biopsies from 2003 to 2015 and were linked to the National Prostate Cancer Register and Prescribed Drug Register. Kaplan-Meier method estimated PC-specific survival and OS, stratified by metastasis at PC diagnosis, and Cox regression estimated hazard ratios (HRs) for Gleason score and T-stage at PC diagnosis and for age and calendar period at CRPC onset by metastasis status at diagnosis. Results: Median OS after CRPC onset was 23.2 months (95% CI = 21.0-25.9) among patients without metastases (M0) at primary diagnosis, and 13.2 months (11.3-14.5) among patients with metastases (M1). Median PC-specific survival from CRPC onset was 30.3 (27.5-34.1) months and 13.3 (12.1-15.8) months for M0 and M1 patients, respectively. Biopsy Gleason score ≥ 8 was associated with higher all-cause mortality than ≤6 (HR = 2.07 [95% CI = 1.43-3.01]) and PC-specific mortality (2.07 [1.27-3.40]) after CRPC among patients with M0 disease. Patients developing CRPC from 2012 onward had lower all-cause mortality (HR = 0.71 [95% CI = 0.60-0.85] [M0]; 0.60 [0.47-0.77] [M1]) and PC-specific mortality (0.73 [0.57-0.94] [M0]; 0.62 [0.46-0.84] [M1]) compared with those prior to 2012. Conclusions: M1 disease at PC diagnosis was associated with worse survival after CRPC onset versus M0. Higher Gleason score at diagnosis was associated with higher mortality after CRPC onset in M0 patients at diagnosis.

Background: While urinary bladder cancer is consistently more common in men worldwide, women have poorer prognosis. The aim of this study was to outline sex differences in prognostic factors and clinical management and to explore whether these can explain the poorer urinary bladder cancer outcome in women., Patients and Methods: We performed a population-based cohort study including all patients diagnosed with urothelial bladder cancer between 1997 and 2014 at age 18 to 89 who had data recorded in the Swedish Urinary Bladder Cancer Register (n = 36,344). Female-to-male odds ratios for clinical management parameters were estimated by logistic regression. To quantify sex differences in bladder cancer-specific survival, we estimated empirical survival proportions and mortality rates as well as applied flexible parametric models to estimate female-to-male hazard ratios and survival proportions over follow-up. Adjusted models included age, year, World Health Organization grade, stage, marital status, education, health care region, birth country, and comorbidity., Results: Except for an adverse stage distribution in women, we found no evidence of unequal clinical management. Among those diagnosed with bladder cancer, women had a higher bladder cancer mortality (adjusted hazard ratio, 1.15; 95% confidence interval, 1.08-1.23) driven by muscle-invasive tumors (adjusted hazard ratio, 1.24; 95% confidence interval, 1.14-1.34). The female survival disadvantage was confined to the first 2 years after diagnosis., Conclusion: The excess bladder cancer mortality in women is limited to those diagnosed with muscle-invasive tumors and cannot be explained by the examined clinicopathologic factors. Further investigations of sex differences in therapeutic procedures and outcomes, including complications, of muscle-invasive bladder cancer, must be performed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Numerous pretreatment risk classification tools are available for prostate cancer. Which tool is best in predicting prostate cancer death is unclear., Objective: To systematically compare the prognostic performance of the most commonly used pretreatment risk stratification tools for prostate cancer., Design, Setting, and Participants: A nationwide cohort study was conducted, including 154 811 men in Prostate Cancer data Base Sweden (PCBaSe) 4.0 diagnosed with nonmetastatic prostate cancer during 1998-2016 and followed through 2016., Outcome Measurements and Statistical Analysis: We compared the D'Amico, National Institute for Health and Care Excellence (NICE), European Association of Urology (EAU), Genito-Urinary Radiation Oncologists of Canada (GUROC), American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), and Cambridge Prognostic Groups (CPG) risk group systems; the Cancer of the Prostate Risk Assessment (CAPRA) score; and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram in predicting prostate cancer death by estimating the concordance index (C-index) and the observed versus predicted cumulative incidences at different follow-up times., Results and Limitations: A total of 139 515 men were included in the main analysis, of whom 15 961 died from prostate cancer during follow-up. The C-index at 10 yr of follow-up ranged from 0.73 (95% confidence interval [CI]: 0.72-0.73) to 0.81 (95% CI: 0.80-0.81) across the compared tools. The MSKCC nomogram (C-index: 0.81, 95% CI: 0.80-0.81), CAPRA score (C-index: 0.80, 95% CI: 0.79-0.81), and CPG system (C-index: 0.78, 95% CI: 0.78-0.79) performed the best. The order of performance between the tools remained in analyses stratified by primary treatment and year of diagnosis. The predicted cumulative incidences were close to the observed ones, with some underestimation at 5 yr. It is a limitation that the study was conducted solely in a Swedish setting (ie, case mix)., Conclusions: The MSKCC nomogram, CAPRA score, and CPG risk grouping system performed better in discriminating prostate cancer death than the D'Amico and D'Amico-derived systems (NICE, GUROC, EAU, AUA, and NCCN). Use of these tools may improve clinical decision making., Patient Summary: There are numerous pretreatment risk classification tools that can aid treatment decision for prostate cancer. We systematically compared the prognostic performance of the most commonly used tools in a large cohort of Swedish men with prostate cancer. The Memorial Sloan Kettering Cancer Center nomogram, Cancer of the Prostate Risk Assessment score, and Cambridge Prognostic Groups performed best in predicting prostate cancer death. The use of these tools may improve treatment decisions., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Men often undergo repeat prostate biopsies because of suspicion of missed cancer. We assessed if (i) methylation of selected genes in prostate tissue vary with aging and (ii) methylation alterations in repeat biopsies predict missed prostate cancer., Methods: We conducted a case-control study among men who underwent at least two negative prostate biopsies followed by a sampling either positive (cases n = 111) or negative (controls n = 129) for prostate cancer between 1995 and 2014 at the University Hospital (Turin, Italy). Two pathology wards were included for replication purposes. We analyzed methylation of GSTP1, APC, PITX2, C1orf114, GABRE, and LINE-1 in the first two negative biopsies. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of the association between genes methylation and prostate cancer., Results: Age at biopsy and time interval between the two negative biopsies were not associated with methylation levels of the selected genes in neither cases nor controls. GSTP1 methylation in the first and in the second negative biopsy was associated with prostate cancer detection [OR per 1% increase: 1.14 (95% CI 1.01-1.29) for the second biopsy and 1.21 (95% CI 1.07-1.37) for the highest methylation level (first or second biopsy)]. A threshold > 10% for GSTP1 methylation corresponded to a specificity of 0.98 (positive likelihood ratio 7.87). No clear association was found for the other genes. Results were consistent between wards., Conclusions: Our results suggest that GSTP1 methylation in negative prostate biopsies is stable over time and can predict missed cancer with high specificity.

Background: It is unclear whether preoperative staging using Magnetic Resonance Imaging (MRI) reduces the risk of positive margins in prostate cancer. We aimed to assess the effect on surgical margins and degree of nerve sparing of a pelvic MRI presented at a preoperative MRI conference., Methods: Single institution, observational cohort study including 1037 men that underwent robot assisted radical prostatectomy between October 2013 and June 2015. Of these, 557 underwent a preoperative MRI combined with a preoperative MRI conference and 410 did not. With whole-mount prostate specimen histopathology as gold standard we assessed the ability of MRI in finding the index tumor and the sensitivity and specificity for extra prostatic extension. We calculated relative risks for positive surgical margins and non-nerve sparing procedure, adjusting for preoperative risk factors using stabilized inverse-probability weighting., Results: MRI detected the index tumor in 80% of the cases. Non-organ confined disease (pT3) at histology was present in the MRI and the non-MRI group in 42% and 24%, respectively. Rate of positive surgical margins comparing the MRI and non-MRI groups was 26.7% and 33.7%, respectively, relative risk 0.79 [95% CI 0.65-0.96], weighted relative risk (wRR) 0.69 [95% CI 0.55-0.86]. The wRR of extensive positive surgical margins was 0.45 [95% CI 0.31-0.67]. Undergoing MRI was also associated with an increased risk of being operated with a non-nerve sparing technique (wRR, 1.84 [95% CI 1.11-3.03])., Conclusions: Our study suggests that preoperative prostate MRI in combination with a preoperative MRI conference affects the degree of nerve-sparing surgery and reduces positive surgical margins.

Context: Until recently, there has been a lack of evidence-based treatment alternatives in men with nonmetastatic castrate-resistant prostate cancer (NM-CRPC). However, new evidence-based treatment alternatives are emerging., Objective: We aimed to describe time-to-event outcomes in NM-CRPC patients based on evidence from both prospective and retrospective studies. Second, we aimed to describe predictors of these outcomes in the same patient population., Evidence Acquisition: A systematic review was conducted to identify clinical studies (both prospective and retrospective) in NM-CRPC patients. All published Kaplan-Meier curves were digitized, and individual participant data were extracted using a published and validated R code. The following outcomes were considered: overall survival (OS), bone metastasis-free survival (BMFS), time to bone metastasis (TTBM), metastasis-free survival, time to metastasis, time to progression (TTP), progression-free survival, and time to prostate-specific antigen (PSA) progression. Second, we described all predictor/outcome relationships., Evidence Synthesis: Median survival times, in months, for OS, BMFS, TTBM, and TTP in placebo arms of randomized clinical trials are 45.3 (95% confidence interval [CI]: 43.5-46.8), 31.5 (95% CI: 28-33.4), 28.8 (95% CI: 25.2-31.6), and 22.2 (95% CI: 19.3-24.8), respectively. In general, reported outcomes in retrospective studies seemed to be longer than those reported in clinical trials. Baseline PSA nadir levels, PSA doubling time, PSA velocity, and alkaline phosphatase velocity are reliable predictors of time-to-event outcomes in NM-CRPC patients, whereas Gleason score is not., Conclusions: NM-CRPC is a long-standing condition where effective treatments to slow down disease progression historically have been lacking. Compared with prospective studies, retrospective studies have had limited ability to correctly identify NM-CRPC patients and estimate time to different outcomes in NM-CRPC patients., Patient Summary: For patients with nonmetastatic castration-resistant prostate cancer (NM-CRPC), currently no effective treatments resulting in longer survival compared with watchful waiting are available. On average, without additional treatment, half of these patients survive <45 mo after NM-CRPC diagnosis., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

In this paper, we describe the Prognostic Factors for Mortality in Prostate Cancer (ProMort) study and use it to demonstrate how the weighted likelihood method can be used in nested case-control studies to estimate both relative and absolute risks in the competing-risks setting. ProMort is a case-control study nested within the National Prostate Cancer Register (NPCR) of Sweden, comprising 1,710 men diagnosed with low- or intermediate-risk prostate cancer between 1998 and 2011 who died from prostate cancer (cases) and 1,710 matched controls. Cause-specific hazard ratios and cumulative incidence functions (CIFs) for prostate cancer death were estimated in ProMort using weighted flexible parametric models and compared with the corresponding estimates from the NPCR cohort. We further drew 1,500 random nested case-control subsamples of the NPCR cohort and quantified the bias in the hazard ratio and CIF estimates. Finally, we compared the ProMort estimates with those obtained by augmenting competing-risks cases and by augmenting both competing-risks cases and controls. The hazard ratios for prostate cancer death estimated in ProMort were comparable to those in the NPCR. The hazard ratios for dying from other causes were biased, which introduced bias in the CIFs estimated in the competing-risks setting. When augmenting both competing-risks cases and controls, the bias was reduced., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In Sweden, human tissue samples obtained from diagnostic and surgical procedures have for decades been routinely stored in a formalin-fixed, paraffin-embedded, form. Through linkage with nationwide registers, these samples are available for molecular studies to identify biomarkers predicting mortality even in slow-progressing prostate cancer. However, tissue fixation causes modifications of nucleic acids, making it challenging to extract high-quality nucleic acids from formalin fixated tissues., Methods: In this study, the efficiency of five commercial nucleic acid extraction kits was compared on 30 prostate biopsies with normal histology, and the quantity and quality of the products were compared using spectrophotometry and Agilent's BioAnalyzer. Student's t-test's and Bland-Altman analyses were performed in order to investigate differences in nucleic acid quantity and quality between the five kits. The best performing extraction kits were subsequently tested on an additional 84 prostate tumor tissues. A Spearman's correlation test and linear regression analyses were performed in order to investigate the impact of tissue age and amount of tissue on nucleic acid quantity and quality., Results: Nucleic acids extracted with RNeasy® FFPE and QIAamp® DNA FFPE Tissue kit had the highest quantity and quality, and was used for extraction from 84 tumor tissues. Nucleic acids were successfully extracted from all biopsies, and the amount of tumor (in millimeter) was found to have the strongest association with quantity and quality of nucleic acids., Conclusions: To conclude, this study shows that the choice of nucleic acid extraction kit affects the quantity and quality of extracted products. Furthermore, we show that extraction of nucleic acids from archival formalin-fixed prostate biopsies is possible, allowing molecular studies to be performed on this valuable sample collection.

Background: To investigate the reliability with which healthcare professionals with different levels of expertise are able to impart the exact location of prostate cancer (PCA) after (A) reading written magnetic resonance imaging (MRI) reports, (B) attending MRI presentations in multidisciplinary team meetings (MDT), and (C) examining 3D printed prostate models, which represents a new technology to describe the location of PCA lesions., Methods: We used three different PCA cases to assess the three information tools. Construct validation was performed using two healthcare groups with different levels of expertise: (1) Nine expert urologists in PCA, and (2) nine medical students. After each information tool, the study participants plotted the tumor location in a 2-dimensional prostate diagram. A scoring system was established to evaluate the drawings in terms of accuracy of plotting tumor position. Data are shown as median scores with interquartile range., Results: Within the expert group, no significant difference was seen in the overall scoring results between the information tools (p = 0.34). Medical students performed significantly worse with MDT information (p = 0.03). Experts performed better in all three information tools compared to students, resulting in a significantly 25% higher overall total score (25.0[22.3-26.7] vs. 20.0[15.0-24.0], p<0.001). The difference was largest after MDT information, with experts showing a 49% better scoring (p<0.001), and second largest with the 3D printed models, showing a 17% better scoring of the experts (p = 0.07). No difference was found in the written MRI report scoring results between experts and students., Conclusions: 3D printed models provided better orientation guide to medical students compared to MDT MRI presentations. This indicates that the 3D printed models might be easier to understand than the current gold standard MDT conferences. Therefore, 3D models may play an increasingly important role in providing guidance for orientation for less experienced individuals, such as surgical trainees., Competing Interests: The authors have declared that no competing interests exist.

Purpose Prostate cancer among first-degree relatives is a strong risk factor for diagnosis of prostate cancer, and the contribution of heritable factors in prostate cancer etiology is high. We investigated how the concordance of non-low-risk prostate cancer among brothers is affected by their genetic relation. Methods We identified 4,262 pairs of brothers with prostate cancer in the Prostate Cancer Database Sweden. Their cancers were categorized as low risk (Gleason score ≤ 6; clinical stage T1-2, Nx/N0, Mx/M0; and prostate-specific antigen ≤ 10 ng/mL) or non-low risk. The odds ratio (OR) for concordance of non-low-risk cancer was calculated with logistic regression for the different types of fraternity (monozygotic twins, dizygotic twins, full brothers, and half-brothers) Results Among monozygotic twins who both were diagnosed with prostate cancer, the OR for both brothers being in the non-low-risk category was 3.82 (95% CI, 0.99 to 16.72) after adjusting for age and year of diagnosis. Among full brothers, the corresponding adjusted OR was 1.21 (95% CI, 1.04 to 1.39). When the analysis was restricted to brothers who both were diagnosed within 4 years, the results were similar. Conclusion Non-low-risk prostate cancer has a heritable pattern suggesting shared genetic factors, with the highest concordance among monozygotic twins. Our results suggest that a man whose brother has been diagnosed with a non-low-risk prostate cancer is at a clinically relevant increased risk of developing an aggressive prostate cancer himself.

Osteonecrosis of the jaws (ONJ) has been associated to antiresorptive treatment and is an increasing problem all over the world. ONJ is a severe adverse effect of antiresorptive treatment with bisphosphonate and denosumab used for treatment of osteoporosis, metastases from certain malignant conditions and as an adjuvant treatment in postmenopausal women with breast cancer, and of treatment with certain chemotherapeutic drugs. In this paper the epidemiology, symptoms, diagnostic features, clinical findings, and treatment are reviewed. Guidelines are presented for dental treatment, surgery and referral of patients on antiresorptive treatment.

Background: Screening for prostate cancer using prostate-specific antigen (PSA) alone leads to un-necessary biopsying and overdiagnosis. PSA density is easily accessible, but early evidence on its use for biopsy decisions was conflicting and use of PSA density is not commonly recommended in guidelines., Methods: We analyzed biopsy outcomes in 5291 men in the population-based STHLM3 study with PSA ≥ 3 ng/ml and ultrasound-guided prostate volume measurements by using percentages and regression models. PSA density was calculated as total PSA (ng/ml) divided by prostate volume (ml). Main endpoint was clinically significant cancer (csPCa) defined as Gleason Score ≥ 7., Results: The median PSA-density was 0.10 ng/ml 2 (IQR 0.075-0.14). PSA-density was associated with the risk of finding csPCa both with and without adjusting for the additional clinical information age, family history, previous biopsies, total PSA and free/total PSA (OR 1.06; 95% CI:1.05-1.07 and OR 1.07, 95% CI 1.06-1.08). Discrimination for csPCa was better when PSA density was added to a model with additional clinical information (AUC 0.75 vs. 0.73, P < 0.05). The proportion of men with Gleason Score 6 (ISUP 1) was similar across stratas of PSA-density. Omitting prostate biopsy for men with PSA-density ≤0.07 ng/ml 2 would save 19.7% of biopsy procedures, while missing 6.9% of csPCa. PSA-density cutoffs of 0.10 ng/ml 2 and 0.15 ng/ml 2 resulted in detection of 77% (729/947) and 49% (461/947) of Gleason Score ≥7 tumors., Conclusions: PSA-density might inform biopsy decisions, and spare some men from the morbidity associated with a prostate biopsy and diagnosis of low-grade prostate cancer.

Background: Robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) treatment has been widely adopted with limited evidence for long-term (>5 yr) oncologic efficacy., Objective: To evaluate long-term oncologic outcomes following RARP., Design, Setting, and Participants: Prospective cohort study of 885 patients who underwent RARP as monotherapy for PCa between 2002 and 2006 in a single European centre and followed up until 2016., Intervention: RARP as monotherapy., Outcome Measurements and Statistical Analysis: Biochemical recurrence (BCR)-free survival (BCRFS), salvage therapy (ST)-free survival (STFS), prostate cancer-specific survival (CSS), and overall survival (OS) were estimated using the Kaplan-Meier method, and event-time distributions were compared using the log-rank test. Variables predictive of BCR and ST were identified using Cox proportional hazards models., Results and Limitations: We identified 167 BCRs, 110 STs, 16 PCa-related deaths, and 51 deaths from other/unknown causes. BCRFS, STFS, CSS, and OS rates were 81.8%, 87.5%, 98.5%, and 93.0%, respectively, at median follow-up of 10.5 yr. On multivariable analysis, the strongest independent predictors of both BCR and ST were preoperative Gleason score, pathological T stage, positive surgical margins (PSMs), and preoperative prostate-specific antigen. PSM >3mm/multifocal but not ≤3mm independently affected the risk of both BCR and ST. Study limitations include a lack of centralised histopathologic reporting, lymph node and post-operative tumour volume data in a historical cohort, and patient-reported outcomes., Conclusions: RARP appears to confer effective long-term oncologic efficacy. The risk of BCR or ST is unaffected by ≤3mm PSM, but further follow-up is required to determine any impact on CSS., Patient Summary: Robot-assisted surgery for prostate cancer is effective 10 yr after treatment. Very small (<3mm) amounts of cancer at the cut edge of the prostate do not appear to impact on recurrence risk and the need for additional treatment, but it is not yet known whether this affects the risk of death from prostate cancer., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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., (© 2017 The Authors. Journal of Surgical Oncology Published by Wiley Periodicals, Inc.)

Purpose To determine the effect of comorbidity on prostate cancer (PCa)-specific mortality across treatment types. Patients and Methods These are the results of a population-based observational study in Sweden from 1998 to 2012 of 118,543 men who were diagnosed with PCa with a median follow-up of 8.3 years (interquartile range, 5.2 to 11.5 years) until death from PCa or other causes. Patients were categorized by patient characteristics (marital status, educational level) and tumor characteristics (serum prostate-specific antigen, tumor grade and clinical stage) and by treatment type (radical prostatectomy, radical radiotherapy, androgen deprivation therapy, and watchful waiting). Data were stratified by Charlson comorbidity index (0, 1, 2, or ≥ 3). Mortality from PCa and other causes and after stabilized inverse probability weighting adjustments for clinical patient and tumor characteristics and treatment type was determined. Kaplan-Meier estimates and Cox proportional hazards regression models were used to calculate hazard ratios. Results In the complete unadjusted data set, we observed an effect of increased comorbidity on PCa-specific and other-cause mortality. After adjustments for patient and tumor characteristics, the effect of comorbidity on PCa-specific mortality was lost but maintained for other-cause mortality. After additional adjustment for treatment type, we again failed to observe an effect for comorbidity on PCa-specific mortality, although it was maintained for other-cause mortality. Conclusion This large observational study suggests that comorbidity affects other cause-mortality but not PCa-specific- mortality after accounting for patient and tumor characteristics and treatment type. Regardless of radical treatment type (radical prostatectomy or radical radiotherapy), increasing comorbidity does not seem to significantly affect the risk of dying from PCa. Consequently, differences in oncologic outcomes that were observed in population-based comparative effectiveness studies of PCa treatments may not be a result of the varying distribution of comorbidity among treatment groups.

Background: Given current drug policy reforms to decriminalize or legalize cannabis in numerous countries worldwide, the current study assesses the relation between cannabis use and the development of testicular cancer. Methods: The study included a population-based sample ( n = 49,343) of young men ages 18-21 years who underwent conscription assessment for Swedish military service in 1969-1970. The conscription process included a nonanonymous questionnaire eliciting information about drug use. Conscription information was linked to Swedish health and administrative registry data. Testicular cancers diagnosed between 1970 and 2011 were identified by International Classification of Diseases-7/8/9/10 testicular cancer codes in the Swedish National Patient Register, the Cancer Register, or the Cause of Death Register. Cox regression modeling was used to estimate the hazards associated with cannabis use and time to diagnosis of testicular cancer. Results: No evidence was found of a significant relation between lifetime "ever" cannabis use and the subsequent development of testicular cancer [ n = 45,250; 119 testicular cancer cases; adjusted HR (aHR), 1.42; 95% confidence interval (CI), 0.83-2.45]. "Heavy" cannabis use (defined as usage of more than 50 times in lifetime, as measured at conscription) was associated with the incidence of testicular cancer ( n = 45,250; 119 testicular cancer cases; aHR 2.57; 95% CI, 1.02-6.50). Conclusions: The current study provides additional evidence to the limited prior literature suggesting cannabis use may contribute to the development of testicular cancer. Impact: Emerging changes to cannabis drug policy should consider the potential role of cannabis use in the development of testicular cancer. Cancer Epidemiol Biomarkers Prev; 26(11); 1644-52. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: There is increasing low-quality evidence rationalizing the use of radical therapy for men at high risk of disseminated prostate cancer., Objective: To investigate, using high-quality epidemiologic data, whether initial radical therapy in men at high risk of disseminated prostate cancer improves survival., Design, Setting, and Participants: An observational population-based Swedish study from 1996 to 2010 of men at high risk of disseminated prostate cancer (prostate-specific antigen [PSA] >50) initially treated by radical therapy (radiation therapy [n=630] or radical prostatectomy [n=120]) or androgen deprivation therapy (n=17 602), and followed for up to 15 yr., Outcome Measurements and Statistical Analysis: Prostate-cancer and other-cause mortality was estimated for the treatment groups. We also matched the two cohorts for grade, T stage, M stage, Charlson score, year of diagnosis, age, and PSA, and found androgen deprivation therapy patient matches for 575 of the radical therapy patients, and then repeated comparative effectiveness analyses., Results and Limitation: Prostate-cancer mortality was substantially greater in the androgen deprivation therapy group compared with the radically treated one, in unmatched (9062/17 602 vs 86/750) and matched (177/575 vs 71/575) cohorts. Among matched cohorts, initial androgen deprivation therapy was associated with nearly three-fold higher hazard of prostate-cancer death compared with initial radical therapy (2.87; 95% confidence interval 2.16-3.82). Multiple sensitivity analyses suggested that the findings were robust, although the general limitations of nonrandomized studies remain. Further, the study cohort may have included men with both systemic and nonsystemic disease, as a sole eligibility criterion of PSA >50 was used., Conclusions: This large and comprehensive population-based study suggests that initial radical therapy in men at high risk of disseminated prostate cancer improves survival., Patient Summary: This large Swedish study suggests that men with prostate cancer that has spread beyond the prostate benefit from treating the prostate itself with radiation therapy or surgery rather than treating the disease with hormones alone., (Copyright © 2017 European Association of Urology. All rights reserved.)

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

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., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Background: Familial prostate cancer risk estimates are inflated by clinically insignificant low-risk cancer, diagnosed after prostate-specific antigen testing. We provide age-specific probabilities of non-low- and high-risk prostate cancer., Methods: Fifty-one thousand, eight hundred ninety-seven brothers of 32 807 men with prostate cancer were identified in Prostate Cancer data Base Sweden (PCBaSe). Nelson-Aalen estimates with 95% confidence intervals (CIs) were calculated for cumulative, family history-stratified probabilities of any, non-low- (any of Gleason score ≥ 7, prostate-specific antigen [PSA] ≥ 10 ng/mL, T3-4, N1, and/or M1) and high-risk prostate cancer (Gleason score ≥ 8 and/or T3-4 and/or PSA ≥ 20 ng/mL and/or N1 and/or M1)., Results: The population probability of any prostate cancer was 4.8% (95% CI = 4.8% to 4.9%) at age 65 years and 12.9% (95% CI = 12.8% to 12.9%) at age 75 years, of non-low-risk prostate cancer 2.8% (95% CI = 2.7% to 2.8%) at age 65 years and 8.9% (95% CI = 8.8% to 8.9%) at age 75 years, and of high-risk prostate cancer 1.4% (95% CI = 1.3% to 1.4%) at age 65 years and 5.2% (95% CI = 5.1% to 5.2%) at age 75 years. For men with one affected brother, probabilities of any prostate cancer were 14.9% (95% CI = 14.1% to 15.8%) at age 65 years and 30.3% (95% CI = 29.3% to 31.3%) at age 75 years, of non-low-risk prostate cancer 7.3% (95% CI = 6.7% to 7.9%) at age 65 years and 18.8% (95% CI = 17.9% to 19.6%) at age 75 years, and of high-risk prostate cancer 3.0% (95% CI = 2.6% to 3.4%) at age 65 years and 8.9% (95% CI = 8.2% to 9.5%) at age 75 years. Probabilities were higher for men with a stronger family history. For example, men with two affected brothers had a 13.6% (95% CI = 9.9% to 17.6 %) probability of high-risk cancer at age 75 years., Conclusions: The age-specific probabilities of non-low- and high-risk cancer presented here are more informative than relative risks of any prostate cancer and more suitable to use for counseling men with a family history of prostate cancer., (Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States.)

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., (© 2015 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Purpose: Physical activity and body mass index (BMI) are involved in prostate cancer etiology; possible biologic mechanisms include their effects on hormonal levels. Our aim was to investigate the relationship between physical activity, obesity, and prostate cancer., Methods: We followed a cohort of 13,109 Swedish men for 13 years and investigated the association of self-reported physical activity and BMI at baseline with prostate cancer incidence. We further analyzed whether BMI could modulate effects of physical activity. Occupational, recreational, and total physical activity were analyzed in relation to overall, localized, and advanced prostate cancer., Results: During the study follow-up, we observed a total of 904 cases of prostate cancer (429 localized, 407 advanced, and 68 unclassified). High levels of occupational physical activity were associated with a nonsignificantly decreased risk of overall (HR 0.81, 95 % CI 0.61-1.07), localized (HR 0.75, 95 % CI 0.51-1.12), and advanced (HR 0.85, 95 % CI 0.55-1.31) prostate cancer. We found no association between high BMI and risk of prostate cancer incidence: We observed, however, a significant interaction between BMI and leisure physical activity., Conclusion: No association was confirmed between total physical activity and localized or advanced prostate cancer. The highest, relative to the lowest, level of occupational physical activity tended to be linked to a lower risk of prostate cancer, with a suggested dose-response relationship. We found no association between high BMI and risk of prostate cancer incidence; however, our analyses suggested an interaction between BMI and physical activity during recreational time that merits further investigation in future studies.

Hypothyroidism in patients with metastatic renal cell carcinoma (mRCC) during treatment with the tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib is a well-established side effect. Furthermore, the potential role of hypothyroidism as predictive marker of outcome has been studied but with conflicting results. The aim of the present meta-analysis was to assess the predictive value of hypothyroidism for progression-free (PFS) and overall survival (OS) in patients with mRCC during TKI therapy. We searched PubMed and the electronic abstract databases of the major international congresses' proceedings to identify all eligible studies that reported a correlation between the development of hypothyroidism during TKI treatment and outcome in patients with mRCC. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS and OS were obtained from these publications and pooled in a meta-analysis. Eleven studies with a total of 500 patients fulfilled the inclusion criteria. We found no statistical significant difference in PFS between patients who developed hypothyroidism during sunitinib therapy and unaffected patients (HR, 0.82; 95% CI, 0.59-1.13; P = .22; 6 studies; 250 patients). The HR for OS was 0.52 (95% CI, 0.31-0.87; P = .01) for patients who developed hypothyroidism during sunitinib therapy compared with patients who did not (4 studies; 147 patients). The development of hypothyroidism during TKI therapy is not clearly shown to be predictive of efficacy in patients with mRCC. The observed advantage in OS for the patients with acquired hypothyroidism should be interpreted with caution., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Many elderly men with high-risk nonmetastatic prostate cancer (HRnMPCa) do not receive radical treatment, despite the high mortality associated with conservative management., Objective: To investigate how age and comorbidity affect treatment of men with HRnMPCa., Design, Setting, and Participants: This was an observational nationwide register study during 2001-2012. We identified 19 190 men of <80 yr of age diagnosed with HRnMPCa in the National Prostate Cancer Register of Sweden and 95 948 age-matched men without prostate cancer in the register of the total population., Outcome Measurements and Statistical Analysis: The outcome was the proportion of men with HRnMPCa receiving radical treatment (radical prostatectomy or radiotherapy). Vital status and the Charlson comorbidity index (CCI) were obtained from nationwide registers. The 10-yr survival of men without prostate cancer, stratified by age and CCI, was used as a measure of the life expectancy of the men with prostate cancer., Results and Limitations: The proportions receiving radical treatment varied with life expectancy among men younger than 70 yr, whereas use of these treatments did not match the long life expectancy of men in their seventies with CCI 0-1. Only 10% of men aged 75-80 yr with CCI 0 received radical treatment despite 52% probability of 10-yr life expectancy, compared with approximately half of the men younger than 70 yr with a similar life expectancy. The use of radical treatment for HRnMPCa increased with time in all Swedish counties, but a threefold difference between counties remained in 2009-2012 for patients aged 70-80 yr with CCI 0-1. Uncertain external validity is a study limitation, and the impact of physician versus patient preferences on treatment selection could not be assessed., Conclusions: Otherwise healthy men in their seventies with HRnMPCa were less likely to receive radical treatment than younger men with a similar life expectancy, although increasing use of radical treatment was observed during the study period. Our findings highlight the need for improved methods for clinical decision-making, including improved assessment of life expectancy., Patient Summary: We performed a nationwide register study that showed that many healthy men in their seventies live for at least another 10 yr. Despite this long life expectancy, men in their seventies with high-risk nonmetastatic prostate cancer were often not treated with radical prostatectomy or radiotherapy, possibly because their life expectancy was underestimated. Our study highlights the need for improved clinical decision-making, which should incorporate an assessment of the patient's life expectancy., (Copyright © 2014 European Association of Urology. All rights reserved.)

Objective: To evaluate the role of positive surgical margin (PSM) size/focality and location in relation to risk of biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP)., Patients and Methods: Clinicopathological data were collected from 904 patients who underwent RARP at a single European institution from 2002 to 2006. PSM status after RARP was defined as cancer cells at the inked margin, and was stratified by size/focality and location. The outcome variable was BCR, defined as a postoperative PSA level of ≥0.2 ng/mL. We modelled clinicopathological covariates including PSM size/focality and location using Cox proportional hazards regression. In subgroup analyses, we assessed the effect of PSM size and location at different pathological stages and grades of disease., Results: Compared with negative SM, a PSM of >3 mm/multifocal was associated with an increased risk of BCR in the entire cohort (hazard ratio [HR] 2.84, 95% confidence interval 1.76-4.59), while unifocal PSMs of ≤3 mm were not significantly associated with BCR. In subgroup analyses, the negative impact of >3 mm/multifocal PSM appeared greatest in those with lower postoperative stage and grade of disease. The prognostic role of PSM location was unconfirmed, although data indicated that posterolateral PSMs may be of lower significance in RARP patients. The study is limited by lack of central pathology review, and lack of statistical adjustment for tumour volume, lymph node status, and surgeon volume., Conclusion: We found that men with >3 mm/multifocal PSMs have a higher risk of BCR than those with unifocal PSMs of ≤3 mm or negative SMs, especially if they have lower risk disease. Posterolateral margins may be of little significance in a RARP population., (© 2013 The Authors. BJU International © 2013 BJU International.)

Background: An association between male fertility and risk of prostate cancer has been suggested, possibly through lower androgen levels in subfertile men. We evaluated male fertility in relation to risk of prostate cancer by assessing the frequency of fathering of dizygotic twins, a marker of high fertility, among cases of prostate cancer and controls., Methods: We performed a case-control study in Prostate Cancer data Base Sweden (PCBaSe), a nationwide, population-based cohort. PCBaSe was linked to the Swedish twin register for information on zygosity for same-sex twins and to other nationwide health care registers and demographic databases for information on socioeconomic factors, comorbidity, and tumor characteristics for 96 301 prostate cancer cases and 378 583 matched controls. To account for the influence of in vitro fertilization on dizygotic twinning, analyses were restricted to men who had fathered children before 1991, when in vitro fertilization was still uncommon in Sweden., Results: 1 112 cases and 4 538 controls had fathered dizygotic twins. Men with dizygotic twins had no increased risk of prostate cancer compared to fathers of singletons; neither for total prostate cancer odds ratio (OR) 0.95(95% CI 0.89-1.02), nor for any risk category, OR 0.97 (95% CI 0.84-1.12) for low-risk disease, and OR 1.04 (95% CI 0.90-1.22) for metastatic disease., Conclusion: The lack of association between fathering of dizygotic twins and prostate cancer risk give no support for an association between male fertility and prostate cancer risk.

Background/purpose: The incidence of infantile hypertrophic pyloric stenosis (IHPS) in Sweden decreased dramatically during the 1990s. The aim of the study was to examine IHPS risk factors and the possible change in them as the incidence declined., Methods: This is a case-control study including 3608 surgically treated IHPS cases and 17588 matched controls during 1973-2008. Cases were identified in the Swedish National Patient Register and data on possible risk factors were collected from the Swedish Medical Birth Register. The association between study variables and IHPS was analyzed using conditional logistic regression for the whole study period and separately for periods with high and low IHPS incidences., Results: Prematurity (OR, 2.54; 95% CI, 2.06-3.14), caesarean delivery (OR, 1.67; 95% CI, 1.51-1.86), maternal smoking (OR, 1.82; 95% CI, 1.53-2.16), and young maternal age (< 20yrs) (OR, 1.42; 95% CI, 1.17-1.73) were associated with an increased IHPS risk. Birth order 2 (OR, 0.78; 95% CI, 0.71-0.85) or more was associated with a lower IHPS risk. ORs for smoking increased at low incidence rate., Conclusion: We report caesarean section, prematurity, primiparity, young maternal age, and smoking as significant IHPS risk factors. The impact of smoking was higher during periods with a low incidence., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To evaluate the risk of different in-hospital complications for patients undergoing a radical cystectomy (RC), as limited nationwide population data on short- and long-term complications after RC is available, despite it being the standard treatment for localised muscle-invasive urinary bladder cancer (UBC)., Patients and Methods: In all, 7608 persons underwent a RC after UBC diagnosis, as registered in the Swedish National Patient Register between 1964 and 2008. We estimated the frequency and incidences and calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariate Cox proportional hazards models., Results: Urinary tract infection/septicaemia was the most common complication following radical cystectomy, with an incidence of 90.4 per 1,000 person years. There was a higher risk of urinary tract infection among patients who had a continent cutaneous reservoir (HR: 1.11 (0.94-1.30) or orthotopic neobladder 1.21 (1.05-1.39) than among those with ileal conduit. Similarly, continent cutaneous reservoir and orthotopic neobladder were associated with increased risks for wound and abdominal wall hernias, stones in the urinary tract, hydronephrosis and nephrostomy tube treatment, and kidney failure. In contrast, risk of bowel obstruction was lower among those with orthotopic neobladder than those with ileal conduit (HR: 0.64 (0.50-0.81)) and those with continent cutaneous reservoir (HR: 0.92 (0.73-1.16)., Conclusions: In-hospital complications after RC are numerous and continue to accumulate for many years after surgery, indicating the need for life-long follow-up of these patients. Comparison between different types of diversion should, however, be made with care because of potential confounding by indication., (© 2013 The Authors. BJU International publihsed by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Hip fractures are associated with increased mortality and are a known adverse effect of androgen deprivation therapy (ADT) for prostate cancer (PCa). It was our aim to evaluate how mortality after hip fracture is modified by PCa and ADT., Methods: PCa dataBase Sweden (PCBaSe 2.0) is based on the National PCa Register and also contains age and county-matched PCa-free men. We selected all men (n = 14,205) who had been hospitalized with a hip fracture between 2006 and 2010; 2,300 men had a prior PCa diagnosis of whom 1,518 (66%) were on ADT prior to date of fracture. Risk of death was estimated with cumulative incidence and standardized mortality ratios (SMRs) to make comparisons with the entire PCa population and the general population., Results: Cumulative incidences indicated that there was a higher risk of death following a hip fracture for PCa men on ADT than for PCa men not on ADT or PCa-free men, particularly in the first year. The SMRs showed that PCa men on ADT with a hip fracture were 2.44 times more likely to die than the comparison cohort of all PCa men (95%CI: 2.29-2.60). This risk was especially increased during the first month (5.64 (95%CI: 4.16-7.48)). In absolute terms, hip fractures were associated with 20 additional deaths per 1,000 person-years in PCa men not on ADT, but 30 additional deaths per 1,000 person-years for PCa men on ADT, compared to all PCa men., Conclusion: Hip fractures are associated with higher all-cause mortality in PCa men on ADT than in PCa men not on ADT or PCa-free men, especially within the first three months.

Previous studies have shown a decreased risk of prostate cancer for childless men; however, the cause of the association remains to be elucidated. The aim of our study was to assess the risk of prostate cancer by fatherhood status, also considering potential confounding factors. In a case-control study in Prostate Cancer data Base Sweden 2.0, a nationwide, population-based cohort, data on number of children, marital status, education, comorbidity and tumor characteristics obtained through nationwide healthcare registers and demographic databases for 117,328 prostate cancer cases and 562,644 controls, matched on birth year and county of residence, were analyzed. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for prostate cancer overall and by risk category, adjusting for marital status and education. Childless men had a decreased risk of prostate cancer compared to fathers, OR = 0.83 (95% CI = 0.82-0.84), and risk was lower for low-risk prostate cancer, OR = 0.74 (95% CI = 0.72-0.77), than for metastatic prostate cancer, OR = 0.93 (95% CI = 0.90-0.97). Adjustment for marital status and education attenuated the association in the low-risk category, adjusted OR = 0.87 (95% CI = 0.84-0.91), whereas OR for metastatic cancer remained virtually unchanged, adjusted OR = 0.92 (95% CI = 0.88-0.96). Our data indicate that the association between fatherhood status and prostate cancer to a large part is due to socioeconomic factors influencing healthcare-seeking behavior including testing of prostate-specific antigen levels., (Copyright © 2013 UICC.)

Objective: This study compared survival after diagnosis of prostate cancer (PC) in men previously treated with finasteride, in men previously treated with α-adrenoceptor antagonists, in men treated with both, and in men who had received neither type of medication., Material and Methods: In total, 3791 men diagnosed with PC in northern Denmark were identified. The region's prescription database was used to identify all men prescribed finasteride and α-adrenoceptor antagonists and those who had received neither medication during the period 1989-2001. Among men with a diagnosis of PC, overall survival and disease-specific survival were assessed after diagnosis using Cox proportional hazards regression. The risk of being diagnosed with non-localized PC was estimated using conditional logistic regression., Results: The adjusted hazard ratio (HR) for PC death and overall death after treatment with finasteride was 0.93 [95% confidence interval (CI) 0.76-1.14] and 0.92 (95% CI 0.77-1.10), respectively. Treatment with α-adrenoceptor antagonists was associated with a reduced risk of PC death and overall death (HR 0.78, 95% CI 0.67-0.90, and 0.82, 95% CI 0.73-0.93, respectively. The risk of being diagnosed with non-localized PC was increased for men taking finasteride (odds ratio 1.14, 95% CI 1.01-1.29) per 100 defined daily doses., Conclusions: Treatment with finasteride prior to a diagnosis of PC did not affect PC-specific survival, but increased the risk of being diagnosed with non-localized disease. Treatment with α-adrenoceptor antagonists was associated with better cause-specific survival and lower risk of non-localized disease.

Background & Aims: Gastroesophageal reflux is common in infants during their first year of life, especially in those born preterm or small for gestational age (SGA). We assessed whether being born preterm or SGA increased the risk of developing Barrett's esophagus (BE) in adulthood., Methods: We performed a population-based case-control study of patients with BE (cases) that were diagnosed at 2 Swedish hospitals from January 1, 1986, through December 31, 2005. We identified the birth hospital of the cases; data on perinatal characteristics such as gestational age at birth and birth weight were collected from original birth records. We also obtained and collected information on the 3 singleton live births, of the same sex, born after each case at the same maternity ward (controls). In total, we analyzed data from 331 cases and 852 matched controls. We used conditional logistic regression to determine odds ratios (ORs), determined 95% confidence intervals (CIs), and adjusted for potential confounding factors., Results: Compared with infants born with a normal birth weight (3000-3999 g), infants with low birth weight (<2500 g) were at increased risk of BE (adjusted OR, 8.22; 95% CI, 2.83-23.88). This was mainly due to an effect of SGA rather than preterm birth. Specifically, compared with infants with normal birth weight for gestational age (25th-75th percentiles), the odds of BE among very SGA infants (<3rd percentile) was nearly tripled (adjusted OR, 2.95; 95% CI, 1.35-6.44)., Conclusions: On the basis of a population-based study of patients with BE in Sweden, infants born SGA have a 3-fold increase in risk for developing BE as adults, compared with infants of normal birth weight for gestational age., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Gastroesophageal reflux is a main risk factor for oesophageal adenocarcinoma (EAC). Infants born preterm or small for gestational age (SGA) regurgitate more than infants born at term, and some data support the hypothesis of an association with oesophagitis, Barrett's oesophagus and EAC. This study aimed to assess the association between risk of EAC and preterm or SGA birth., Methods: In this population-based case-control study, all incident cases of EAC in Sweden between 1st January 1998 and 31st December 2004 with retrievable birth records were eligible as cases. We sampled three matched controls per case from the birth ledger at the same delivery ward as the respective case. Data on gestational age, birth weight and other perinatal exposures were extracted from the original birth records. For comparison, we collected perinatal data for cases of cardia adenocarcinoma and oesophageal squamous cell carcinoma and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated., Results: The risk of EAC increased by 13% per week of shorter duration of gestation (OR 1.1, 95%CI 1.0-1.3), while SGA did not influence the risk. No effect of preterm birth or SGA was found on the risk of cardia adenocarcinoma or oesophageal squamous cell carcinoma., Conclusion: Preterm birth, but not SGA, might lead to an increased risk of EAC as an adult., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: Studies of cancer patient survival typically report relative survival or cause-specific survival using data from patients diagnosed many years in the past. From a risk-communication perspective, such measures are suboptimal for several reasons; their interpretation is not transparent for non-specialists, competing causes of death are ignored and the estimates are unsuitable to predict the outcome of newly diagnosed patients. In this paper, we discuss the relative merits of recently developed alternatives to traditionally reported measures of cancer patient survival., Methods: In a relative survival framework, using a period approach, we estimated probabilities of death in the presence of competing risks. To illustrate the methods, we present estimates of survival among 23,353 initially untreated, or hormonally treated men with intermediate- or high-risk localized prostate cancer using Swedish population-based data., Results: Among all groups of newly diagnosed patients, the probability of dying from prostate cancer, accounting for competing risks, was lower compared to the corresponding estimates where competing risks were ignored. Accounting for competing deaths was particularly important for patients aged more than 70 years at diagnosis in order to avoid overestimating the risk of dying from prostate cancer., Conclusions: We argue that period estimates of survival, accounting for competing risks, provide the tools to communicate the actual risk that cancer patients, diagnosed today, face to die from their disease. Such measures should offer a more useful basis for risk communication between patients and clinicians and we advocate their use as means to answer prognostic questions.

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.)

There are only few studies of the association between preterm birth and risk of chronic lung disease in old age. The aim of this study was to assess the association between poor fetal growth, preterm birth, sex and risk of asthma and Chronic Obstructive Pulmonary Disease (COPD) in adulthood. We have followed up a cohort of all infants born preterm (<35 weeks) or with low birth weight (<2,000 and <2,100 g for girls and boys, respectively) and an equal number of controls in a source population of 250,000 individuals born from 1925 through 1949 in Sweden (6,425 subjects in total). Cases of asthma and COPD were identified through the Swedish Patient Register and we considered cohort subjects as cases if they had a main or additional discharge diagnosis of asthma or COPD. For any obstructive airways disease, there was a statistically significant increase in risk with decreasing birth weight and gestational duration among women but not among men. Compared to women born at term, women born before 32 weeks of gestation had a hazard ratio for any obstructive airways disease and asthma of 2.77 (95% CI 1.39-5.54) and 5.67 (1.73-18.6), respectively. Low birth weight and preterm birth are risk factors for obstructive airways disease also among the old, but the importance of these risk factors differs between the sexes.

Background & Aims: The association between gastroesophageal reflux and esophageal adenocarcinoma is likely to be mediated by inflammation. Reflux is common in infancy; the esophageal mucosa of infants born preterm or small for gestational age (SGA) could be particularly vulnerable. We investigated the association between preterm or SGA birth and risk of esophagitis early in life., Methods: We analyzed data from the Swedish birth register and the Swedish patient register to identify birth characteristics of individuals with endoscopically verified esophagitis from 1973 to 2007 and to determine their outcomes (7358 cases). Five controls were selected randomly and matched with each case (N = 38,479). Multivariable conditional logistic regression models were used to provide odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounding., Results: The risk of esophagitis was increased among individuals born preterm (≤32 gestational weeks) (OR, 2.74; 95% CI, 2.15-3.49) or SGA (OR, 1.49; 95% CI, 1.32-1.68). When data were stratified by age at diagnosis and by sex, different risk patterns appeared. Among individuals diagnosed with esophagitis 9 years of age and younger, the OR for prematurity was 6.82 (95% CI, 4.65-10.03) and the OR for SGA at birth was 1.98 (95% CI, 1.55-2.52). Furthermore, the association with preterm birth was stronger among males (OR, 9.88; 95%, CI 5.93-16.45) than females (OR, 3.41; 95% CI, 1.81-6.41), whereas the association with SGA was stronger among females (OR, 2.50; 95% CI, 1.76-3.55) than males (OR, 1.64; 95% CI, 1.16-2.30). The risk of being diagnosed with esophagitis at age 20 or younger was not associated with preterm birth (OR, 1.02; 95% CI, 0.64-1.63), but was associated with being SGA at birth (OR, 1.31; 95% CI, 1.11-1.54)., Conclusions: Preterm birth is associated with esophagitis only during childhood, whereas SGA birth is associated with esophagitis during adolescence as well. The associations appear to differ between sexes., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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: 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.)

Introduction: In contrast to research in adults, there have been limited studies on testicular germ-cell cancer among boys aged <15 years. The aim of the study was to investigate the association between perinatal characteristics and childhood testicular germ-cell cancer., Methods: We identified 152 patients with childhood germ-cell cancer among boys (<15 years) born in Norway, Sweden, Finland and Denmark between 1967 and 2006 using the cancer and medical birth registries. For each case we sampled 10 population controls matched on year and country of birth. We used conditional logistic regression analysis to estimate odds ratios for cancer risk., Results: There was a weak, positive association between high (≥4000 g) birth weight and childhood testicular germ-cell cancer (adjusted OR=1.25; 95% CI: 0.83-1.90) compared with normal birth weight, and a correspondingly elevated risk for low birth weight (adjusted OR=1.41; 95% CI: 0.43-4.56). For Ponderal Index (PI) there was an increased risk for low and high values compared to those in the middle category (adjusted OR=1.64; 95% CI: 1.03-2.62 and 1.67; 95% CI: 0.93-2.99), respectively. There was no association between birth length and childhood testicular germ-cell cancer. The adjusted OR for testicular cancer among first born was 1.40; 95% CI: 0.96-2.05. Greater maternal age and less maternal education appeared to increase the risk, but the estimates were not statistically significant., Conclusion: We found a U-shaped association between fetal growth, measured as the PI, and childhood testicular germ-cell cancer. Our findings support the notion that abnormal fetal growth rate confers a risk in pediatric testicular cancer [corrected]., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment., Objective: To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent., Design, Setting, and Participants: We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis., Measurements: We followed up the patient cohort in the Cause of Death Register for ≤ 11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics., Results and Limitations: The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25-32%) for Gleason score (GS) 2-6, 41% (95% CI, 38-44%) for GS 7, 52% (95% CI, 47-57%) for GS 8, and 64% (95% CI, 59-69%) for GS 9-10. Even for men aged >85 yr at diagnosis with GS 8-10, PCa was a major cause of death: 42% (95% CI, 37-47%). Men with locally advanced disease and a PSA<4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status., Conclusions: The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: Experimental evidence indicates that prolactin might play a role in tumorigenesis of several human cancers, but data on cancer risk in hyperprolactinemia patients are sparse. The aim of this study was to investigate cancer risk in hyperprolactinemia patients. Design A population-based matched cohort study in Sweden., Methods: The hyperprolactinemia cohort consisted of patients hospitalized for hyperprolactinemia from 1987 to 1995 identified in the National Patient Register (n=585) and a hospital cohort of prolactinoma patients at Karolinska University Hospital (n=384). For each patient, ten matched individuals were identified via the Register of Population. Cancer occurrence was ascertained via the Swedish Cancer Registry. Hazard ratios (HRs) were estimated by Cox proportional hazards regression., Results: Seventy-three malignant tumors were identified in the hyperprolactinemia patients and 660 tumors in the comparison group (HR 1.31; 95% confidence interval (CI): 1.02-1.68), mainly attributed to an increased risk of upper gastrointestinal cancer in both males and females (HR 3.69; 95% CI: 1.70-8.03) and hematopoietic cancer in females (HR 3.51; 95% CI: 1.06-11.6). Twelve breast cancers occurred in the female patients, corresponding to an HR of 1.09 (95% CI: 0.60-1.99). Prostate cancer risk in hyperprolactinemia men was reduced (HR 0.40; 95% CI: 0.16-0.99)., Conclusions: An increased overall cancer risk was found in hyperprolactinemia patients, but no increased risk of breast cancer in women and a reduced risk of prostate cancer in men. These findings warrant further investigations and to be confirmed in larger studies but may indicate the importance of an active treatment strategy and follow-up of hyperprolactinemia patients.