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Objective To assess the impact of positive surgical margins (PSMs) on long-term outcomes after radical prostatectomy (RP), including metastasis, castrate-resistant prostate cancer (CRPC), and prostate cancer-specific mortality (PCSM). Patients and Methods Retrospective study of 4 051 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort treated by RP from 1988 to 2013. Proportional hazard models were used to estimate hazard ratios (HRs) of PSMs in predicting biochemical recurrence (BCR), CRPC, metastases, and PCSM. To determine if PSMs were more predictive in certain patients, analyses were stratified by pathological Gleason score, stage, and preoperative prostate-specific antigen (PSA) level. Results The median (interquartile range) follow-up was 6.6 (3.2-10.6) years and 1 127 patients had >10 years of follow-up. During this time, 302 (32%) men had BCR, 112 (3%) developed CRPC, 144 (4%) developed metastases, and 83 (2%) died from prostate cancer. There were 1 600 (40%) men with PSMs. In unadjusted models, PSMs were significantly associated with all adverse outcomes: BCR, CRPC, metastases and PCSM (all P ≤ 0.001). After adjusting for demographic and pathological characteristics, PSMs were associated with increased risk of only BCR (HR 1.98, P < 0.001), and not CRPC, metastases, or PCSM (HR ≤1.29, P > 0.18). Similar results were seen when stratified by pathological Gleason score, stage, or PSA level, and when patients who underwent adjuvant radiotherapy were excluded. Conclusions PSMs after RP are not an independent risk factor for CRPC, metastasis, or PCSM overall or within any subset. In the absence of other high-risk features, PSMs alone may not be an indication for adjuvant radiotherapy.

Objectives: To examine the association between body mass index (BMI) and aggressive biochemical recurrence (BCR) using the Shared Equal Access Regional Cancer Hospital (SEARCH) database., Material and Methods: We identified 4123 men with complete data treated by radical prostatectomy between 1988 and 2015. We tested the association between BMI and BCR using Cox models, and among men with BCR, prostate-specific antigen doubling time (PSADT) was compared across BMI categories using linear regression. Models were adjusted for age, race, prostate-specific antigen, biopsy Gleason score, clinical stage, year and surgical centre., Results: Overall, 922 men (22%) were of normal weight (BMI <25 kg/m 2 ), 1863 (45%) were overweight (BMI 25-29.9 kg/m 2 ), 968 (24%) were obese (BMI 30-34.9 kg/m 2 ), and 370 (9%) were moderately or severely obese (BMI ≥35 kg/m 2 ). After adjustment for multiple clinical characteristics, higher BMI was significantly associated with higher risk of BCR (P = 0.008). Among men with BCR, men in the four BMI categories had similar multivariable-adjusted PSADT values (increasing BMI categories: 20.9 vs 21.3 vs 21.0 vs 14.9 months; P = 0.48)., Conclusion: While we confirmed that higher BMI was associated with BCR, we found no link between BMI and PSADT at the time of recurrence. Our data suggest obese men do not have more aggressive recurrences. Future studies are needed to test whether obesity predicts response to salvage therapies., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Objective: To evaluate biochemical recurrence (BCR) patterns amongst men undergoing radical prostatectomy (RP) with specimens having negative (NSM), positive (PSM), and close surgical margins (CSM) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort, as PSM after RP are a significant predictor of biochemical failure and possible disease progression, with CSM representing a diagnostic challenge for surgeons., Patients and Methods: Men undergoing RP between 1988 and 2015 with known final pathological margin status were evaluated. The cohort was divided into three groups based on margin status; NSM, PSM, and CSM. CSM were defined by distance of tumour ≤1 mm from the surgical margin. BCR was defined as a prostate-specific antigen (PSA) level of >0.2 ng/mL, two values at 0.2 ng/mL, or secondary treatment for an elevated PSA level. Predictors of BCR, metastases, and mortality were analysed using Cox proportional hazard models., Results: Of 5515 men in the SEARCH database, 4337 (79%) men met criteria for inclusion in the analysis. Of these, 2063 (48%) had NSM, 1902 (44%) had PSM, and 372 (8%) had CSM. On multivariable analysis, relative to NSM, men with CSM had a higher risk of BCR (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.25-1.82; P < 0.001) but a decreased risk of BCR when compared to those men with PSM (HR 2.09, 95% CI 1.86-2.36; P < 0.001). Metastases, prostate cancer-specific mortality and all-cause mortality did not differ based on margin status alone., Conclusions: Management of men with CSM is a diagnostic challenge, with a disease course that is not entirely benign. The evaluation of other known risk factors probably provides greater prognostic value for these men and may ultimately better select those who may benefit from adjuvant therapy., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Objective: To assess whether obesity is associated with progression to metastasis, prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM), in patients with non-metastatic castration-resistant prostate cancer (non-mCRPC). At the population level, obesity is associated with prostate cancer mortality; however, some studies have found that higher body mass index (BMI) is associated with better long-term prostate cancer outcomes amongst men with mCRPC., Patients and Methods: We identified 1 192 patients with non-mCRPC from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BMI was calculated from height and weight abstracted from the medical records at the time closest to but prior to CRPC diagnosis and categorised as underweight (<21 kg/m 2 ), normal weight (21-24.9 kg/m 2 ), overweight (25-29.9 kg/m 2 ), and obese (≥30 kg/m 2 ). Competing risks regression and Cox models were used to test associations between obesity and progression to metastasis, PCSM, and ACM, accounting for confounders., Results: Overall, 51 (4%) men were underweight, 239 (25%) were normal weight, 464 (39%) were overweight, and 438 (37%) were obese. In adjusted analysis, higher BMI was significantly associated with reduced ACM (hazard ratio [HR] 0.98, P = 0.012) but not PCSM (HR 1.00, P = 0.737) or metastases (HR 0.99, P = 0.225). Likewise, when BMI was treated as a categorical variable in adjusted models, obesity was not associated with PCSM (HR 1.11, P = 0.436) or metastases (HR 1.06, P = 0.647), but was associated with decreased ACM (HR 0.79, P = 0.016) compared to normal weight. No data were available on treatments received after CRPC diagnosis., Conclusions: Amongst patients with non-mCRPC obesity was associated with better overall survival. Although this result mirrors evidence from men with mCRPC, obesity was not associated with prostate cancer outcomes. Larger studies are needed to confirm these findings., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Objectives: To examine whether prostate-specific antigen doubling time (PSADT) correlates with metastases, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) and to identify PSADT thresholds that can be used clinically for risk stratification in men with M0 castration-resistant prostate cancer (CRPC)., Materials and Methods: We collected data on 441 men with M0 CRPC in 2000-2015 at five Veterans Affairs hospitals. Cox models were used to test the association between log-transformed PSADT and the development of metastasis, ACM and PCSM. To identify thresholds, we categorized PSADT into 3-month groups and then combined groups with similar hazard ratios (HRs)., Results: The median (interquartile range) follow-up was 28.3 (14.7-49.1) months. As a continuous variable, PSADT was associated with metastases, ACM and PCSM (HR 1.40-1.68, all P < 0.001). We identified the following PSADT thresholds: <3 months; 3-8.9 months; 9-14. months; and ≥15 months. As a categorical variable, PSADT was associated with metastases, ACM and PCSM (all P < 0.001). Specifically, PSADT <3 months was associated with an approximately ninefold increased risk of metastases (HR 8.63, 95% CI 5.07-14.7) and PCSM (HR 9.29, 95% CI 5.38-16.0), and a 4.7-fold increased risk of ACM (HR 4.71, 95% CI 2.98-7.43) on multivariable analysis compared with PSADT ≥15 months. The median times to metastasis for patients with PSADT <3, 3-8.9, 9-14.9 and ≥15 months were 9, 19, 40 and 50 months, respectively., Conclusion: Prostate-specific antigen doubling time was a strong predictor of metastases, ACM and PCSM in patients with M0 CRPC. As with patients at earlier disease stages, <3, 3-8.9, 9-14.9 and ≥15 months are reasonable PSADT thresholds for risk stratification in men with M0 CRPC. These thresholds can be used for selecting high-risk men for clinical trials., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Objective: To evaluate change in platelet count as an indicator of response to primary tyrosine kinase inhibitor (TKI) therapy for metastatic renal cell carcinoma (mRCC)., Patients and Methods: We conducted a multicentre retrospective analysis of patients with mRCC undergoing primary TKI therapy from May 2005 to August 2014. Change in platelet count was defined as post-treatment platelet count after the first cycle of treatment minus the pretreatment platelet count. Response Evaluation Criteria in Solid Tumours were used to define partial response (PR), stable disease (SD) and progressive disease (PD). Analysis was conducted between subgroups with stable/increased (+ΔPlt) and decreased (-ΔPlt) counts. The primary outcome was overall survival (OS), determined using Kaplan-Meier analysis. Multivariable analysis was conducted for risk factors associated with PD., Results: A total of 115 patients with mRCC were analysed, of whom 19 (16.6%) had a +ΔPlt and 96 (83%) a -ΔPlt. More patients with a +ΔPlt had a Karnofsky score <80 (42.1 vs 14.6%; P = 0.005) and >2 metastatic sites (78.9 vs 51%; P = 0.041). More patients with +ΔPlt than with -ΔPlt had PD (89.4 vs 19.1%; P < 0.001) and more of those with -ΔPlt than with +ΔPlt had SD/PR (80.9 vs 10.6%; P < 0.001). Multivariable analysis showed that +ΔPlt (odds ratio [OR] 5.36, P < 0.001), Karnofsky score < 80 (OR 2.96, P = 0.002) and >2 metastatic sites at presentation (OR 1.87, P = 0.013) were risk factors for PD. Kaplan-Meier analysis showed a lower 5-year OS in patients with +ΔPlt than in those with -ΔPlt (23 vs 53%; P < 0.0001). +ΔPlt had a sensitivity of 48.6%, a specificity of 97.4%, a positive predictive value of 89.5% and a negative predictive value of 80.9% for PD., Conclusions: Patients with a -ΔPlt were more likely to respond to TKI therapy and had longer OS. +ΔPlt above baseline had a high specificity for PD after primary TKI. Further investigation is required to determine the utility of ΔPlt., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Objectives: To test the external validity of a previously developed risk table, designed to predict the probability of a positive bone scan among men with non-metastatic (M0) castration-resistant prostate cancer (CRPC), in a separate cohort., Patients and Methods: We retrospectively analysed 429 bone scans of 281 patients with CRPC, with no known previous metastases, treated at three Veterans Affairs Medical Centers. We assessed the predictors of a positive scan using generalized estimating equations. Area under the curve (AUC), calibration plots and decision-curve analysis were used to assess the performance of our previous model to predict a positive scan in the current data., Results: A total of 113 scans (26%) were positive. On multivariable analysis, the only significant predictors of a positive scan were log-transformed prostate-specific antigen (PSA): hazard ratio (HR) 2.13; 95% confidence interval (CI) 1.71-2.66 (P < 0.001) and log-transformed PSA doubling time (PSADT): HR 0.53; 95% CI 0.41-0.68 (P < 0.001). Among men with a PSA level <5 ng/mL, the rate of positive scans was 5%. The previously developed risk table had an AUC of 0.735 to predict positive bone scan with excellent calibration, and provided additional net benefit in the decision-curve analysis., Conclusion: We have validated our previously developed table to predict the risk of a positive bone scan among men with M0/Mx CRPC. Use of this risk table may allow better tailoring of patients' scanning to identify metastases early, while minimizing over-imaging. Regardless of PSADT, positive bone scans were rare in men with a PSA <5 ng/mL., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Objective: To determine whether there are subsets of men with pathological high grade prostate cancer (Gleason score 8-10) with particularly high or low 2-year biochemical recurrence (BCR) risk after radical prostatectomy (RP) when stratified into groups based on combinations of pathological features, such as surgical margin status, extracapsular extension (ECE) and seminal vesicle invasion (SVI)., Materials and Methods: We identified 459 men treated with RP with pathological Gleason score 8-10 prostate cancer in the SEARCH database. The men were stratified into five groups based on pathological characteristics: group 1, men with negative surgical margins (NSMs) and no ECE; group 2, men with positive surgical margin (PSMs) and no ECE; group 3, men with NSMs and ECE; group 4, men with PSMs and ECE; and group 5, men with SVI. Cox proportional hazards models and the log-rank test were used to compare BCR among the groups., Results: At 2 years after RP, pathological group was significantly correlated with BCR (log-rank, P < 0.001) with patients in group 5 (+SVI) having the highest BCR risk (66%) and those in group 1 (NSMs and no ECE) having the lowest risk (14%). When we compared groups 2, 3, and 4, with each other, there was no significant difference in BCR among the groups (~50% 2-year BCR risk; log-rank P = 0.28). Results were similar when adjusting for prostate-specific antigen, age, pathological Gleason sum and clinical stage, or after excluding men who received adjuvant therapy., Conclusions: In patients with high grade (Gleason score 8-10) prostate cancer after RP, the presence of either PSMs, ECE or SVI was associated with an increased risk of early BCR, with a 2-year BCR risk of ≥50%. Conversely, men with organ-confined margin-negative disease had a very low risk of early BCR despite Gleason score 8-10 disease., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Objectives: To determine if men with adverse pathology but undetectable ultrasensitive (<0.01 ng/mL) PSA are at high-risk for biochemical recurrence (BCR), or if there is a subset of patients at low-risk for whom the benefit of adjuvant radiation therapy might be limited., Patients and Methods: We evaluated 411 patients treated with RP from 2001 to 2013 without adjuvant radiation who had an undetectable (<0.01 ng/mL) PSA level after RP but with adverse pathology [positive surgical margins (PSMs), extraprostatic extension (EPE), and/or seminal vesicle invasion (SVI)]. Multivariable Cox regression analyses tested the relationship between pathological characteristics and BCR to identify groups of men at highest risk of early BCR., Results: On multivariable analysis, only pathological Gleason 7 (4 + 3), Gleason ≥8, and SVI independently predicted BCR (P = 0.019, P < 0.001, and P = 0.001, respectively), although on two-way analysis men with Gleason 7 (4 + 3) did not have significantly higher rates of BCR compared with patients with Gleason ≤6 (log-rank, P = 0.074). Men with either Gleason ≥8 (with PSMs or EPE) or SVI (15% of the cohort) defined a high-risk group vs men without these characteristics (3-year BCR risk of 50.4% vs 11.9%, log-rank, P < 0.001)., Conclusions: Among men with adverse pathology but an undetectable (<0.01 ng/mL) PSA level after RP, the benefits of adjuvant radiation are probably limited except for men with Gleason 8-10 (with PSMs or EPE) or SVI who are at high-risk of early BCR., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Objective: To examine the incidence of and risk factors for development of hyperlipidaemia in patients undergoing radical nephrectomy (RN) or partial nephrectomy (PN) for renal cortical neoplasms, as hyperlipidaemia is a major source of morbidity in chronic kidney disease (CKD)., Patients and Methods: We conducted a two-centre retrospective analysis of 905 patients (mean age 57.5 years, mean follow-up 78 months), who underwent RN (n = 610) or PN (n = 295) between July 1987 and June 2007. Demographics, preoperative and postoperative hyperlipidaemia were recorded. De novo hyperlipidaemia was defined as that ocurring ≥6 months after surgery in cases where laboratory values met National Cholesterol Education Program Adult Treatment Panel III definitions. The Kaplan-Meier method was used to assess freedom from de novo hyperlipidaemia. Multivariable analysis was conducted to determine the risk factors for de novo hyperlipidaemia., Results: There were no significant differences with respect to demographics, preoperative glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) (P = 0.123) and hyperlipidaemia (P = 0.144). Tumour size (cm) was significantly larger in the RN group vs the PN group (7.0 vs 3.7; P < 0.001). Significantly greater postoperative GFR <60 mL/min/1.73 m(2) was noted in the RN group (45.7 vs 18%, P < 0.001). Significantly, more de novo hyperlipidaemia developed in the RN group than in the PN group (23 vs 6.4%; P < 0.001). The mean time to development of hyperlipidaemia was longer for PN than for RN (54 vs 44 months; P = 0.03). Five-year freedom from de novo hyperlipidaemia probability was 76% for RN vs 96% for PN (P < 0.001). Multivariable analysis showed that RN (odds ratio [OR] 2.93; P = 0.0107), preoperative GFR <60 mL/min/1.73 m(2) (OR 1.98; P = 0.037) and postoperative GFR <60 mL/min/1.73 m(2) (OR 7.89; P < 0.001) were factors associated with hyperlipidaemia development., Conclusion: Patients who underwent RN had a significantly higher incidence of and shorter time to development of de novo hyperlipidaemia. RN and pre- and postoperative eGFR <60 mL/min/1.73 m(2) were associated with development of hyperlipidaemia. Further follow-up and prospective investigation are necessary to confirm these findings., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objective: To investigate the effect of statin use after radical prostatectomy (RP) on biochemical recurrence (BCR) in patients with prostate cancer who never received statins before RP., Patients and Methods: We conducted a retrospective analysis of 1146 RP patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analyses were used to examine differences in risk of BCR between post-RP statin users vs nonusers. To account for varying start dates and duration of statin use during follow-up, post-RP statin use was treated as a time-dependent variable. In a secondary analysis, models were stratified by race to examine the association of post-RP statin use with BCR among black and non-black men., Results: After adjusting for clinical and pathological characteristics, post-RP statin use was significantly associated with 36% reduced risk of BCR (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.47-0.87; P = 0.004). Post-RP statin use remained associated with reduced risk of BCR after adjusting for preoperative serum cholesterol levels. In secondary analysis, after stratification by race, this protective association was significant in non-black (HR 0.49, 95% CI 0.32-0.75; P = 0.001) but not black men (HR 0.82, 95% CI 0.53-1.28; P = 0.384)., Conclusion: In this retrospective cohort of men undergoing RP, post-RP statin use was significantly associated with reduced risk of BCR. Whether the association between post-RP statin use and BCR differs by race requires further study. Given these findings, coupled with other studies suggesting that statins may reduce risk of advanced prostate cancer, randomised controlled trials are warranted to formally test the hypothesis that statins slow prostate cancer progression., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objective: To examine the association between diabetes and metastasis risk after radical prostatectomy (RP) and to determine if race or obesity modifies this relationship., Patients and Methods: Patients comprised 2058 US veterans with prostate cancer (PCa) enrolled in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database and treated with RP between 1988 and 2010. The association of diabetes with metastasis risk or secondary treatment rates was examined using Cox proportional hazards, adjusting for preoperative and, separately, clinical and postoperative findings. The effect modification by race (black vs white) and obesity (body mass index [BMI] ≥30 vs <30 kg/m(2) ) was tested via interaction terms., Results: Men with diabetes had higher BMIs and were more likely to be non-white (all P ≤ 0.001). On multivariable analysis, diabetes was not associated with metastasis risk (P ≥ 0.45), but, among men with diabetes, longer diabetes duration was associated with higher metastasis risk (P ≤ 0.035). When stratified by obesity, diabetes was linked with higher metastasis risk in obese but not in non-obese men (P-interaction ≤ 0.037), but there was no significant interaction with race (P-interaction ≥ 0.56). Diabetes also predicted more aggressive secondary treatment among obese men but less aggressive treatment among non-obese men (hazard ratio 1.39 vs 0.63, P-interaction = 0.006). Where applicable, results were similar for both pre- and postoperative models., Conclusions: Diabetes was not associated with metastasis risk overall. Stratification by obesity yielded significant differences, with diabetes linked to a fourfold higher metastasis risk in obese men, despite predicting more aggressive secondary treatment. Longer diabetes duration was also associated with increased metastasis risk., (© 2013 BJU International.)

Unlabelled: Study Type - Therapy (prospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Erectile dysfunction (ED) is a form of endothelial dysfunction that is prevalent in patients with chronic kidney disease (CKD). We hypothesized that partial nephrectomy (PN) would limit development of ED compared with radical nephrectomy (RN), primarily due to renal function preservation, and found that patients undergoing RN had significantly higher de novo ED compared with a contemporary, well-matched cohort undergoing PN; in addition to RN, hypertension, CKD and diabetes mellitus were associated with developing ED. To our knowledge, this is the first study demonstrating an increased risk of ED after RN compared with PN., Objectives: •  To evaluate prevalence and risk factors for development of erectile dysfunction (ED) in patients who underwent radical nephrectomy (RN) and partial nephrectomy (PN). •  ED is a form of endothelial dysfunction that is prevalent in patients with chronic kidney disease (CKD). PN confers superior renal functional preservation compared with RN; however, the impact on ED is unclear., Methods: •  This was a retrospective study of 432 patients (264 RN/168 PN, mean age 58 years, mean follow-up 5.8 years) who underwent surgery for renal tumours between January 1998 and December 2007. •  The primary outcome was rate of de novo ED postoperatively. Secondary outcomes included development of CKD (estimated GFR < 60 mL/min/1.73 m(2) ) and response to phosphodiesterase-5 inhibitors. •  Multivariate analysis was performed to determine risk factors for de novo ED postoperatively., Results: •  RN and PN groups had similar demographics and comorbidities. •  Tumour size (cm) was larger for RN (RN 7.0 vs PN 3.7, P < 0.001) and more preoperative ED existed in PN vs RN (P= 0.042). No differences were observed for preoperative CKD, hyperlipidaemia and diabetes mellitus. •  Postoperatively, higher rates of de novo ED (29.5% vs 9.5%, P < 0.001) and CKD (33.0% vs 9.8%, P < 0.001) developed in RN vs PN cohorts, respectively. •  Of men with ED, 63% responded to phosphodiesterase inhibitors, without significant difference between the two groups (P= 0.896). •  Multivariate analysis demonstrated de novo ED to be associated with RN (odds ratio [OR] 3.56, P < 0.001), hypertension (OR 2.32, P= 0.014), preoperative (OR 8.77, P < 0.001) and postoperative (OR 2.64, P= 0.001) CKD, and postoperative diabetes mellitus (OR 2.93, P < 0.001)., Conclusions: •  Patients undergoing RN had significantly higher de novo ED compared with a contemporary, well-matched cohort undergoing PN. In addition to RN, hypertension, CKD and diabetes mellitus were associated with developing ED. •  Further investigation on effects of surgically induced nephron loss on ED is requisite., (© 2012 BJU INTERNATIONAL.)

Unlabelled: Study Type - Prognosis (cohort series). Level of Evidence 2a. What's known on the subject? and What does the study add? The incidence and prevalence of obesity in the USA and Europe is increasing. Higher body mass index is associated with a lower risk of overall prostate cancer diagnosis but also with an increased risk of high grade prostate cancer. Obese men undergoing primary therapy with radical prostatectomy or external beam radiation are more likely to experience a biochemical recurrence after treatment compared with normal weight men. Finally, obesity is associated with increased prostate-cancer-specific mortality. We hypothesized that obese men on androgen deprivation therapy may be at increased risk for prostate cancer progression. Previous studies have shown that obese men have lower levels of testosterone compared with normal weight men. Additionally, one previous study found that obese men have higher levels of testosterone on androgen deprivation therapy. Men with higher levels of testosterone on androgen deprivation therapy are at increased risk of prostate cancer progression. We found that men with higher body mass index were at increased risk of progression to castration-resistant prostate cancer, development of metastases and prostate-cancer-specific mortality. When we adjusted for various clinicopathological characteristics, obese men were at increased risk of progression to castration-resistant prostate cancer and development of metastases. The results of our study help generate hypotheses for further study regarding the mechanisms between obesity and aggressive prostate cancer., Objective: • To investigate whether obesity predicts poor outcomes in men starting androgen deprivation therapy (ADT) before metastasis, since previous studies found worse outcomes after surgery and radiation for obese men., Methods: • A retrospective review was carried out of 287 men in the SEARCH database treated with radical prostatectomy between 1988 and 2009. • Body mass index (BMI) was categorized to <25, 25-29.9 and ≥ 30 kg/m2. • Proportional hazards models were used to test the association between BMI and time to castration-resistant prostate cancer (PC), metastases and PC-specific mortality adjusting for demographic and clinicopathological data., Results: • During a median 73-month follow-up after radical prostatectomy, 403 men (14%) received early ADT. • Among 287 men with complete data, median BMI was 28.3 kg/m2. • Median follow-up from the start of ADT was 52 months during which 44 men developed castration-resistant PC, 34 developed metastases and 24 died from PC. • In multivariate analysis, higher BMI was associated with a trend for greater risk of progression to castration-resistant PC (P= 0.063), a more than threefold increased risk of developing metastases (P= 0.027) and a trend toward worse PC-specific mortality (P= 0.119). • Prognostic biomarkers did not differ between BMI groups., Conclusions: • Among men treated with early ADT, our results suggest that obese men may have increased risk of PC progression. • These data support the general hypothesis that obesity is associated with aggressive PC, although validation of these findings and further study of the mechanisms linking obesity and poor PC outcomes are required., (© 2011 BJU INTERNATIONAL.)

Objective: To examine the incidence of and risk factors for the development of anaemia and erythropoiesis-stimulation agent (ESA) treatment in patients undergoing radical nephrectomy (RN) and partial nephrectomy (PN) because anaemia is a significant cause of morbidity in chronic kidney disease., Patients and Methods: The study comprised a retrospective review of 905 patients (610 RN/295 PN; mean age, 57.5 years; mean follow-up, 6.4 years) who underwent surgery for renal tumours at two institutions from July 1987 to June 2007. Demographics, disease characteristics and pre- and postoperative (i.e. renal function, metabolic parameters, anaemia and ESA treatment) were recorded. Data were analyzed within subgroups based on treatment (RN vs PN). Multivariate analysis was conducted to determine the risk factors for developing anaemia after surgery., Results: Tumour size (cm) was significantly larger for RN (RN 7.0 vs PN 3.7; P < 0.001). No significant differences were noted with respect to demographics and preoperative anaemia (RN 16.4% vs PN 18.6%; P = 0.454) and ESA-treatment (RN 0.7% vs PN 1.4%; P = 0.499). After surgery, significantly less de novo anaemia (PN 4.1% vs RN 17.5%; P < 0.001) and ESA utilization (PN 2.7% vs RN 13.4%; P < 0.001) occurred in the PN cohort. Multivariate analysis showed that age ≥60 years (odds ratio, OR, 1.62; P = 0.008), African American ethnicity (OR, 2.30; P < 0.001), smoking (OR, 1.60; P = 0.013), glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) (OR, 4.09; P < 0.001), ≥1+ proteinuria (OR, 2.19; P < 0.03), metabolic acidosis (OR, 4.08; P = 0.007) and RN (OR, 2.58; P < 0.001) were significantly associated with de novo anaemia., Conclusions: Patients who underwent RN had a significantly higher prevalence of anaemia and ESA-treatment compared to a well-matched cohort that underwent PN. In addition to RN, age ≥60 years, African American ethnicity, history of smoking, GFR < 60 mL/min/1.73 m(2), proteinuria and metabolic acidosis were associated with developing anaemia., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objectives: • To better understand the natural history of weight change with androgen-deprivation therapy (ADT), we investigated the effect of ADT on body weight among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. • Men undergoing ADT lose lean muscle but gain fat mass, contributing to an overall gain in weight., Patients and Methods: • We identified 132 men in SEARCH who received ADT after radical prostatectomy. • 'Weight change' was defined as the difference in weight before starting ADT (6 months before ADT) and the on-ADT weight (between 6 and 18 months after starting ADT). • In a subanalysis, baseline characteristics of weight-gainers and -losers were analysed using univariate and multivariate analysis to test association with weight change., Results: • In all, 92 men (70%) gained weight, and 40 (30%) either lost or maintained a stable weight. • On average, weight on ADT was 2.2 kg higher than the weight before ADT, with the mean change for weight-gainers and -losers being +4.2 kg and -2.4 kg, respectively. • This compared with no significant weight change in the year before starting ADT (paired t-test, change -0.7 kg, P= 0.19) or in the second year on ADT (paired t-test, change -0.5 kg, P= 0.46) for 84 men in whom these additional weight values were recorded. • There was no significant association between any of the features examined and weight change on univariate and multivariate analysis., Conclusion: • In this longitudinal study, ADT was accompanied by significant weight gain (+2.2 kg). This change occurred primarily in the first year of therapy, with men neither losing nor gaining additional weight thereafter., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: To evaluate the incidence and risk factors for bladder neck contracture (BNC) in men treated with robot-assisted laparoscopic radical prostatectomy (RALP) and open radical prostatectomy (ORP), as BNC is a well-described complication of ORP and may be partially attributable to technique., Patients and Methods: The University of California San Francisco Urologic Oncology Database was queried for patients undergoing RALP or ORP from 2002 to 2008. Patient demographics, prostate cancer-specific information, surgical data, and follow-up were collected. For each surgical approach, multivariate Cox proportional hazards regression was performed to evaluate associations of demographics and clinical characteristics with BNC. Time to BNC after RP was evaluated using life table and Kaplan-Meier methods., Results: From 2002 to 2008, 988 patients underwent RP as primary treatment and had at least 12 months of follow-up. Of these men, 695 underwent ORP and 293 underwent RALP. The mean (sd) age was 59.3 (6.80) years and 91% of men were Caucasian. D'Amico risk groups at diagnosis were low (38%), intermediate (38%), and high (24%). The BNC incidence was 2.2% (22 cases) overall, 1.4% (four) for RALP, and 2.6% (18) for ORP (P= 0.12). Patients with BNC were diagnosed a median (range) of 4.7 (1-15) months after surgery. At 18 months after surgery, the BNC-free rate was 97% for ORP and 99% for RALP (log-rank P= 0.13). The most common presenting complaint was slow stream, followed by urinary retention. In Cox proportional hazards regression analysis, earlier year of surgery, older age at diagnosis and higher PSA level at diagnosis were significantly associated with BNC among ORP patients. In the RALP group, none of the covariates were associated with BNC., Conclusions: The overall incidence of BNC was low in both RALP and ORP groups. Technical factors such as enhanced magnification and a running bladder anastomosis may explain the lower BNC incidence in the RALP group., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Objective: To investigate efficacy of neoadjuvant tyrosine kinase-inhibitor therapy (TKI) before imperative nephron-sparing surgery (NSS), as NSS in patients with large locally advanced or centrally located tumours can be challenging, and TKI therapy might result in a reduction of primary tumour burden and increase the feasibility of NSS., Patients and Methods: This was a multicentre retrospective review and prospective pilot study of patients undergoing neoadjuvant sunitinib before planned NSS from February 2006 to February 2009. All patients underwent confirmatory biopsy for clear cell renal cell carcinoma. Patients received two 28-day cycles of sunitinib before NSS. Demographics/tumour characteristics, tumour response (by the Response Evaluation Criteria In Solid Tumors), outcomes and complications were analysed., Results: Twelve patients (seven men and five women; mean age 60.1 years, tumours on 14 renal units) were given TKI before NSS for imperative indications. The mean pretreatment tumour diameter was 7.1 cm; all patients had a decrease in size of the primary tumour after TKI, with a mean reduction in maximum diameter of 1.5 cm (21.1%). Four of 14 and 10 of 14 primary tumours had a partial response and stable disease after TKI. NSS was achievable in all 14 kidneys. Four patients had a concurrent metastasectomy. The mean warm ischaemia time was 22.5 min; postoperative dialysis was not required in any patients. Final pathology revealed negative tumour margins in all 14 tumours. The mean creatinine and estimated glomerular filtration rate (before/after NSS) were 1.34/1.40 mg/dL (P = 0.431) and 57.7/53.4 mL/min/1.73 m(2) (P = 0.475), respectively. At a mean follow-up of 23.9 months, 10 of the 12 patients were alive, one died from metastatic RCC and none required dialysis. Three of the 14 renal units developed delayed urinary leaks, all in patients who also received postoperative sunitinib. All leaks resolved with conservative measures., Conclusions: Neoadjuvant TKI followed by NSS is safe and feasible, with all patients achieving a reduction in maximum tumour diameter, and with NSS being achievable with negative margins and with no requirement for postoperative dialysis. Further investigation is required., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Objectives: To define a level of persistently elevated prostate-specific antigen (PSA) after radical prostatectomy (RP) that equates with high-risk for disease progression, and to identify preoperative predictors of PSA persistence among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database., Patients and Methods: A total of 901 men treated with RP between 2001 and 2008 were separated into groups based upon PSA nadir within 6 months after RP. We explored the association between nadir groups and time to biochemical recurrence (BCR) using multivariate Cox proportional hazards and determined the preoperative predictors of PSA persistence using logistic regression., Results: Relative to men with undetectable PSA levels, those with a PSA nadir of 0.03 (hazard ratio [HR] 3.88, P < 0.001), 0.04 (HR 4.87, P < 0.001), 0.05-0.09 (HR 12.69, P < 0.001), 0.1-0.19 (HR 13.17, P < 0.001), and 0.2 ng/mL (HR 13.23, P < 0.001) were at increased risk of BCR while men with a nadir of 0.01 (HR 1.36, P = 0.400) and 0.02 (HR 1.64, P = 0.180) were not. Using the PSA persistence definition of a PSA nadir > or = 0.03 ng/mL, 230 men (26%) had persistence. The independent preoperative predictors of PSA persistence were higher body mass index (BMI, P = 0.002), pathological Gleason score (relative to 2-6: 4 + 3-10, P = 0.001) and preoperative PSA level (P < 0.001)., Conclusions: Men with a PSA nadir > or = 0.03 ng/mL after RP were at higher risk for BCR. Using a PSA persistence definition of a PSA nadir > or = 0.03 ng/mL, persistence was predicted by known factors associated with aggressive disease (tumour grade, PSA level and BMI). Validation of the present definition in different populations using later end-points remains necessary to assess its prognostic usefulness.

Objective: To re-calibrate the previously published Duke Prostate Center (DPC) nomogram for the prediction of biochemical recurrence (BCR) after radical prostatectomy (RP) to not only predict overall BCR but also the clinically more relevant endpoint of an aggressive recurrence (i.e. a BCR with a postoperative PSA doubling time (PSADT) of <9 months)., Patients and Methods: Using the established point-scale system based upon the previously published DPC nomogram, we re-calibrated this point system to predict not just BCR, but also aggressive BCR within 2599 men treated with RP from the DPC database. PSADT was computed on all patients meeting the recurrence definition who had a minimum of two PSA values, separated by at least 3 months, and < or =2 years after recurrence. External validation was performed using data from 1695 men treated with RP within the Shared Equal Access Regional Cancer Hospital (SEARCH) database by calculating the concordance index c and by plotting calibration curves., Results: The median follow-up for patients with no BCR was 56 and 47 months for DPC and SEARCH, respectively. In the DPC modelling cohort and the SEARCH validation cohort, 645 (25%) and 557 (33%) men had BCR, while 83 (3.2%) and 71 (4.2%) patients had an aggressive recurrence. In external validation, predictive accuracy for an aggressive BCR was high (c = 0.83) and the nomogram showed good calibration., Conclusions: We re-calibrated an existing nomogram to not only predict overall BCR after RP but also aggressive recurrence after RP. Our new tool can provide valuable information for patient counselling and patient selection for adjuvant therapy trials.

Study Type: Diagnosis (exploratory cohort)., Level of Evidence: 2b., Objective: To clarify the relationship between estimated blood loss (EBL) and biochemical recurrence, assessed by prostate-specific antigen (PSA) level, as blood loss is a long-standing concern associated with radical prostatectomy (RP), and no studies to date have examined the association between blood loss and cancer control., Patients and Methods: In all, 1077 patients were identified in the Shared Equal-Access Regional Cancer Hospital database who underwent retropubic RP (between 1998 and 2008) and had EBL and follow-up data available. We examined the relationship between EBL and recurrence using multivariate Cox regression analyses., Results: Increased EBL was correlated with PSA recurrence in a multivariate-adjusted model (P = 0.01). When analysed by 500-mL EBL categories, those with an EBL of <1500 mL had a similar risk of recurrence. However, the risk of PSA recurrence tended to increase for an EBL of 1500-3499 mL, before decreasing again for patients with an EBL of > or =3500 mL. Men with an EBL of 2500-3499 mL had more than twice the risk of recurrence than men with an EBL of <1500 mL (P = 0.02). EBL was not associated with adverse tumour stage, grade or margin status., Conclusions: There was a significant correlation between EBL at the time of RP and biochemical recurrence. We hypothesized that this association might be due to transfusion-related immunosuppression, excessive blood obscuring the operative field, EBL being a marker of aggressive disease, or EBL being a marker of poor surgical technique. However, our data did not completely fit any one of these hypotheses, and thus the ultimate cause for the increased risk of recurrence remains unclear and requires further study.

Objective: To investigate the predictors of secondary treatment for recurrent prostate cancer after radical prostatectomy (RP) among subjects from the Shared Equal Access Regional Cancer Hospital (SEARCH) database., Patients and Methods: We used Kaplan-Meier curves and Cox proportional hazard models to identify factors associated with time to secondary treatment and type of secondary treatment received among 697 men who developed biochemical recurrence (BCR) after RP., Results: During a median follow-up of 45 months after BCR, 357 men received salvage treatment. The 1-, 3-, and 5-year risk of receiving any salvage treatment was 29% (95% confidence interval (CI) 26-33%), 48% (95%CI 44-52%), and 53% (95%CI 49-57%), respectively. In multivariate analysis, more recent year of recurrence, centre, shorter disease-free interval, and pathological high-grade disease (Gleason 8-10) predicted increased risk of salvage treatment (all P < 0.01). Predictors of specifically receiving radiotherapy were shorter disease-free interval, centre, and more recent year of BCR (all P < 0.001). Predictors of specifically receiving hormonal therapy were shorter disease-free interval, more recent year of BCR, centre, high Gleason score, and higher tumour stage (all P < 0.05). In a subset analysis of men with available prostate-specific antigen doubling time (PSADT) data, shorter PSADT predicted receipt of any salvage treatment as well as radiation and hormonal therapy separately. CONCLUSIONS; Among men who recur after RP, salvage treatment was associated with disease severity, centre and year of BCR; patient-specific factors (race, body mass index and age) were not predictive of secondary treatment. Although patients are being treated more aggressively in contemporary years, the affect on long-term survival is unknown.

Objective: To compare rates of lymph node dissection (LND) and nodal yields between patients treated with open radical retropubic prostatectomy (ORRP) and robot-assisted RRP (RARP) in a contemporary single-institution series., Patients and Methods: Data from 1278 consecutive patients (716 ORRP and 562 RARP) from one institution were accrued prospectively in an institutional database, and the data analysed retrospectively. Disease risk was assessed using the Cancer of the Prostate Risk Assessment (CAPRA) score. The likelihood of LND, nodal yield, and likelihood of node positivity were compared between ORRP and RARP., Results: Of patients treated with ORRP and RARP, 47.8% and 31.8% had LND, respectively, with more receiving LND over time in both surgical approaches. Men undergoing LND had a higher disease risk than those not undergoing LND (mean CAPRA score 4.3 vs 2.1, P < 0.01), and there was no difference in risk between those undergoing ORRP or RARP (mean CAPRA score 3.0 vs 2.9, P = 0.29). The mean (sd) nodal yield was 14.4 (8.7) for ORRP and 9.3 (5.4) for RARP (P < 0.01). Among patients undergoing LND, 5.8% of ORRP and 4.1% of RARP patients had positive nodes (P < 0.01)., Conclusions: The indications for LND and template dissection should be the same regardless of surgical approach. The nodal yield was adequate using both approaches; the yield was higher among ORRP than RARP patients, but the difference was not large, and is less remarkable than the wide variation in yield within each approach. Several factors might explain this variation.

Objective: To determine if prostate-specific antigen doubling time (PSADT), calculated from the first detectable PSA level after radical prostatectomy (RP) to the first PSA level of >or=0.2 ng/mL (early PSADT or ePSADT), correlated with 'standard' PSADT (henceforth PSADT) calculated using values >or=0.2 ng/mL, as a short PSADT following biochemical recurrence (BCR) after RP portends a poor prognosis and poor response to salvage treatment but this is based upon PSADT calculated using PSA values of >or=0.2 ng/mL., Patients and Methods: We used Spearman's correlation to determine the correlation between ePSADT and PSADT among 157 men in the Shared Equal Access Regional Cancer Hospital database who underwent RP between 1988 and 2005 and had a calculable ePSADT and PSADT. We systematically examined ePSADT thresholds and their positive and negative predictive values (PPV and NPV, respectively), to predict aggressive recurrences (PSADT of <9 months)., Results: ePSADT was significantly, though poorly, correlated with PSADT (r = 0.30, P < 0.001). ePSADT more accurately predicted PSADT among men with a long ePSADT. Of men with an ePSADT of >or=20 or >or=15 months, the NPV for an aggressive recurrence was 98% and 93%, respectively. However, among men with an ePSADT of <3 months, the PPV for aggressive recurrence was only 39%., Conclusions: Although ePSADT and PSADT were significantly related, the overall correlation was poor. This was highlighted by the finding that only 39% of men with the shortest ePSADT (<3 months) had a PSADT of <9 months. However, a long ePSADT correlated well with a long PSADT and is thus useful in identifying men at low risk for prostate cancer-specific mortality very early in their BCR.

Objective: To externally validate the nomogram published by Stephenson et al. (termed the 'Stephenson nomogram') to predict disease progression after salvage radiotherapy (SRT) among patients with prostate cancer from the Shared Equal Access Regional Cancer Hospital (SEARCH) database., Patients and Methods: We analysed data from 102 men treated with SRT for prostate-specific antigen (PSA) failure after prostatectomy, of whom 30 (29%) developed disease progression after SRT during a median follow-up of 50 months. The predicted 6-year progression-free survival (PFS) was compared to the actuarial PFS using calibration plots. The accuracy of the nomogram to risk-stratify men for progression was assessed by the concordance index., Results: The median PSA and PSA doubling time before SRT was 0.6 ng/mL and 10.3 months, respectively. The 6-year actuarial disease-free progression after SRT was 57% (95% confidence interval 42-69%). The overall concordance index of the Stephenson nomogram was 0.65. The nomogram predicted failure more accurately at the extremes of risk (lowest and highest) but in intermediate groups, the accuracy was less precise. Of the 11 variables used in the nomogram, only negative margins and high PSA level before SRT were significantly associated with increased disease progression., Conclusion: The Stephenson nomogram is an important tool to predict disease progression after SRT following radical prostatectomy. It adequately predicted progression in SEARCH with reasonable accuracy. Also, in SEARCH, disease progression was predicted by similar disease characteristics. However, the overall modest performance of the model in our validation cohort indicates there is still room for improvement in predictive models for disease progression after SRT.

Objective: To investigate and report the clinicopathological characteristics and outcomes after radical prostatectomy (RP) in patients with prostate cancer and previous exposure to Agent Orange (AO), particularly in relationship to race., Patients and Methods: In 1495 veterans who had undergone RP the clinicopathological characteristics, biochemical progression rates, and prostate-specific antigen (PSA) doubling time (DT) after recurrence between AO-exposed and unexposed men were compared using logistic and linear regression and Cox proportional hazards analyses, and stratified by race., Results: The 206 (14%) men with AO exposure were more likely to be black (P = 0.001), younger (P < 0.001), treated more recently (P < 0.001), have a higher body mass index (P = 0.001), have clinical stage T1 disease (P < 0.001), and have lower preoperative PSA levels (P = 0.001). After adjusting for several clinical characteristics, AO exposure was not significantly related to adverse pathological features but was significantly associated with biochemical progression risk (relative risk 1.55, 95% confidence interval 1.15-2.09, P = 0.004) and shorter PSADT (P < 0.001) after recurrence (8.2 vs 18.6 months). When stratified by race, these associations were present and similar in both races, with no significant interaction between race and AO exposure for predicting biochemical recurrence or mean adjusted PSADT (P interaction >0.20)., Conclusions: Patients with AO exposure and treated with RP were more likely to be black, present with lower risk features, have an increased risk of biochemical progression, and shorter PSADT after recurrence. When stratified by race, the association between AO exposure and poor outcomes was present in both races. These findings suggest that among selected men who choose RP, AO exposure might be associated with more aggressive prostate cancer.

Objective: To compare the predictive accuracy (PA) of existing models in estimating risk of biochemical recurrence (BCR) vs aggressive recurrence (BCR with a prostate-specific antigen, PSA, doubling time, DT, of <9 months)., Patients and Methods: The study included 1550 men treated with radical prostatectomy (RP) between 1988 and 2007 within the Shared Equal Access Regional Cancer Hospital database. The PA of nine different risk stratification models for estimating risk of BCR and risk of aggressive recurrence after RP was assessed using the concordance index, c., Results: The 10-year risks of BCR and aggressive recurrence were 47% and 9%, respectively. Across all nine models tested, the PA was a mean (range) of 0.054 (0.024-0.074) points higher for predicting aggressive recurrence than for predicting BCR alone (c = 0.756 vs 0.702). Similar results were obtained in four sensitivity analyses: (i) defining patients with BCR but unavailable PSADT (220) as having aggressive recurrence; (ii) defining these patients as not having aggressive recurrence; (iii) defining aggressive recurrence as a PSADT of <6 months; or (iv) defining aggressive recurrence as a PSADT of <12 months. The improvement in PA was greater for preoperative than for postoperative models (0.053 vs 0.036, P = 0.03)., Conclusion: Across nine different models the prediction of aggressive recurrence after RP was more accurate than the prediction of BCR alone. This is probably because current models mainly assess cancer biology, which correlates better with aggressive recurrence than with BCR alone. Overall, all models had relatively similar accuracy for predicting aggressive recurrence.

Objective: To test the hypothesis that the association between prostate size and risk of Gleason grade upgrading varies as a function of sampling., Patients and Methods: We examined the association between pathological prostate weight, prostate biopsy scheme and Gleason upgrading (Gleason > or =7 at radical prostatectomy, RP) among 646 men with biopsy Gleason 2-6 disease treated with RP between 1995 and 2007 within the Shared Equal Access Regional Cancer Hospital Database using logistic regression. In all, 204 and 442 men had a sextant (six or seven cores) or extended-core biopsy (eight or more cores), respectively. Analyses were adjusted for centre, age, surgery, preoperative prostate-specific antigen level, clinical stage, body mass index, race, and percentage of cores positive for cancer., Results: In all, 281 men (44%) were upgraded; a smaller prostate was positively associated with the risk of upgrading in men who had an extended-core biopsy (P < 0.001), but not among men who had a sextant biopsy (P = 0.22). The interaction between biopsy scheme and prostate size was significant (P interaction = 0.01)., Conclusions: These data support the hypothesis that the risk of upgrading is a function of two opposing contributions: (i) a more aggressive phenotype in smaller prostates and thus increased risk of upgrading; and (ii) more thorough sampling in smaller prostates and thus decreased risk of upgrading. When sampled more thoroughly, the phenotype association dominates and smaller prostates are linked with an increased risk of upgrading. In less thoroughly sampled prostates, these opposing factors nullify, resulting in no association between prostate size and risk of upgrading. These findings help to explain previously published disparate results of the importance of prostate size as a predictor of Gleason upgrading.

Objective: To indirectly test the hypothesis that prostate-specific antigen (PSA)-based screening is biased against obese men due to haemodilution of PSA, and thus results in delayed diagnosis and poorer outcome beyond the biological link between obesity and aggressive prostate cancer., Patients and Methods: We sought to examine the association between body mass index (BMI) and the outcome of radical prostatectomy (RP) separately for men with PSA-detected cancers (cT1c) or with abnormal digital rectal examination (DRE) findings (cT2/T3), and stratified by year of treatment, using two large databases. We conducted a retrospective cohort study of 1375 and 2014 men treated by RP between 1988 and 2007 using the Shared Equal Access Regional Cancer Hospital (SEARCH) and Duke Prostate Center (DPC) databases. We evaluated the association between BMI and adverse pathological features and biochemical progression, using logistic regression and Cox proportional hazards models, adjusting for several clinical characteristics, respectively. Data were examined as a whole and as stratified by clinical stage (cT1c vs cT2/T3) and year of surgery (>or=2000 vs <2000)., Results: In both cohorts a higher BMI was associated with high-grade disease (P 0.3). Among men with T1c disease, the association between BMI and biochemical progression was limited to men treated in 2000 or later (P 0.4)., Conclusions: Obese men with PSA-detected cancers and treated with RP since 2000 were at significantly greater risk of biochemical progression, while obese men treated before 2000 or diagnosed with an abnormal DRE were not at significantly greater risk of progression. These findings support the hypothesis that current PSA-based screening is less effective at finding cancers in obese men, leading to more aggressive tumours at diagnosis. Lowering the PSA threshold for biopsy among obese men might help to improve outcomes among this high-risk group.

Objectives: To determine if there is predilection for any specific anatomical location of positive surgical margins (PSMs) after radical prostatectomy (RP) for prostate cancer in obese men, as previous studies found that obesity was associated with an increased risk of PSMs., Patients and Methods: We analysed retrospectively 1434 men treated with RP between 1989 and 2007 within the Shared Equal Access Regional Cancer Hospital database. The association between increased body mass index (BMI) and overall and site-specific PSMs was assessed using multivariate logistic regression., Results: After adjusting for several preoperative clinical and pathological characteristics, a higher BMI was associated with an increased risk of PSMs both overall and at all specific anatomical locations (all P or=35 kg/m2, there was more variation, with the highest excess risk of PSMs at the bladder neck and apex., Conclusions: Obesity was associated with an increased risk of overall PSMs and at all anatomical locations. Although the excess risk of PSMs was similar across all anatomical locations, there was a suggestion of a higher risk of apical margins among the most obese men, which if validated, further supports the importance of the apical dissection in all men and suggests added difficulty in obese patients.