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OBJECTIVE: To evaluate the relationship between pre-operative PSA value, 68Ga-prostate-specific-membrane-antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa). PATIENTS AND METHODS: The study included 164 patients diagnosed with ≤2 pelvic lymph-node recurrence(s) of PCa documented on 68Ga-PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high-volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (1.5 ng/ml). Clinical recurrence (CR)-free survival after sLND was calculated using multivariable analyses and plotted over pre-operative PSA value. RESULTS: Median [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre-operative PSA value, with highest rates for patients with pre-operative PSA > 1.5 ng/ml (pelvic-only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre-operative PSA was associated with PSA response (p

The numbers needed to image to identify pelvic lymph node and/or distant metastases in newly diagnosed prostate cancer (PCa) patients according to risk level are unknown.Relying on Surveillance, Epidemiology, and End Results (2010-2016), we tabulated rates and proportions of patients with (a) lymph node or (b) distant metastases according to National Comprehensive Cancer Network (NCCN) risk level and calculated the number needed to image (NNI) for both endpoints. Multivariable logistic regression analyses were performed.Of 145,939 newly diagnosed PCa patients assessable for analyses of pelvic lymph node metastases (cN1), 4559 (3.1%) harbored cN1 stage: 13 (0.02%), 18 (0.08%), 63 (0.3%), 512 (2.8%), and 3954 (14.9%) in low, intermediate favorable, intermediate unfavorable, high, and very high-risk levels. These resulted in NNI of 4619, 1182, 319, 35, and 7, respectively. Of 181,109 newly diagnosed PCa patients assessable for analyses of distant metastases (M1Our observations perfectly validated the NCCN recommendations for imaging in newly diagnosed high and very high-risk PCa patients. However, in unfavorable intermediate-risk PCa patients, in whom bone and soft tissue imaging is recommended, the NNI might be somewhat elevated to support routine imaging in clinical practice.

Multiparametric MRI (mpMRI) has demonstrated high diagnostic accuracy for clinically significant PCa (csPCa). However, the accuracy of this test in men that received a previous prostatic surgery is still controversial. We aimed at assessing the effect of previous prostatic surgery on the detection of csPCa in a tertiary referral center.We relied on a cohort of 311 men with a positive mpMRI (prostate imaging - reporting and data system [PI-RADS] ≥ 3) who underwent a targeted (TBx) plus concomitant systematic random biopsy (SBx) at a single tertiary referral center between 2017 and 2020. The study outcome was to compare the detection of csPCa (Gleason score ≥ 3 + 4) between the two groups (no previous prostate surgery [Group 1] vs. previous prostate surgery [Group 2]). Multivariable logistic regression analysis (MVA) was used to assess the relationship between previous prostate surgery and the detection of csPCa at TBx, after taking into account potential clinical confounders.Overall, 24 (8%) patients received a previous prostate surgery before undergoing mpMRI. Median prostate-specific antigen density was 0.15 versus 0.08 ng/ml/cc, in Group 1 versus 2, respectively. The most frequent finding at mpMRI was in Group 1 versus 2, PI-RADS 4 (55%) versus PI-RADS 3 and 4 (42% each). The majority of patients were biopsy naïve in both Groups 1 (66%) and 2 (71%). The overall detection of csPCa in Group 1 versus 2 was 83% versus 75%, respectively. Differently, the detection of csPCa at TBx in Groups 1 versus 2 was 76% versus 71%, respectively. At MVA, previous prostate surgery (odds ratio: 0.65; p = 0.02) was significantly associated with lower csPCa detection at TBx, after accounting for potential confounders.The presence of previous prostate surgery significantly decreases the accuracy of mpMRI in detecting csPCa. These results should be taken into account when assessing patients with a history of prostatic surgery and a suspicious lesion at mpMRI, to better select those who might avoid an unnecessary biopsy.

Contemporary seminal vesicle invasion (SVI) rates in National Cancer Comprehensive Network (NCCN) high-risk prostate cancer (PCa) patients are not well known but essential for treatment planning. We examined SVI rates according to individual patient characteristics for purpose of treatment planning.Within Surveillance, Epidemiology, and End Results (SEER) database (2010-2015), 4975 NCCN high-risk patients were identified. In the development cohort (SEER geographic region of residence: South, North-East, Mid-West, n = 2456), we fitted a multivariable logistic regression model predicting SVI. Its accuracy, calibration, and decision curve analyses (DCAs) were then tested versus previous models within the external validation cohort (SEER geographic region of residence: West, n = 2519).Out of 4975 patients, 28% had SVI. SVI rate ranged from 8% to 89% according to clinical T stage, prostate-specific antigen (PSA), biopsy Gleason Grade Group and percentage of positive biopsy cores. In the development cohort, these variables were independent predictors of SVI. In the external validation cohort, the current model achieved 77.6% accuracy vs 73.7% for Memorial Sloan Kettering Cancer Centre (MSKCC) vs 68.6% for Gallina et al. Calibration was better than for the two alternatives: departures from ideal predictions were 6.0% for the current model vs 9.8% for MSKCC vs 38.5% for Gallina et al. In DCAs, the current model outperformed both alternatives. Finally, different nomogram cutoffs allowed to discriminate between low versus high SVI risk patients.More than a quarter of NCCN high-risk PCa patients harbored SVI. Since SVI positivity rate varies from 8% to 89%, the currently developed model offers a valuable approach to distinguish between low and high SVI risk patients.

To compare overall mortality (OM), cancer-specific mortality (CSM), and other cause mortality (OCM) rates between radical prostatectomy (RP) versus radiotherapy (RT) in clinical node-positive (cN1) prostate cancer (PCa).Within Surveillance, Epidemiology, End Results (SEER) (2004-2016), we identified 4685 cN1 PCa patients, of whom 3589 (76.6%) versus 1096 (24.4%) were treated with RP versus RT. After 1:1 propensity score matching (PSM), Kaplan-Meier plots and Cox regression models tested the effect of RP versus RT on OM, while cumulative incidence plots and competing-risks regression (CRR) models addressed CSM and OCM between RP and RT patients. All analyses were repeated after the inverse probability of treatment weighting (IPTW). For CSM and OCM analyses, the propensity score was used as a covariate in the regression model.Overall, RT patients were older, harbored higher prostate-specific antigen values, higher clinical T and higher Gleason grade groups. PSM resulted in two equally sized groups of 894 RP versus 894 RT patients. After PSM, 5-year OM, CSM, and OCM rates were, respectively, 15.4% versus 25%, 9.3% versus 17%, and 6.1% versus 8% for RP versus RT (all p 0.001) and yielded respective multivariate hazard ratios (HRs) of 0.63 (0.52-0.78, p 0.001), 0.66 (0.52-0.86, p 0.001), 0.71 (0.5-1.0, p = 0.05), all favoring RP. After IPTW, Cox regression models yielded HR of 0.55 (95% confidence interval [CI] = 0.46-0.66) for OM, and CRR yielded HRs of 0.49 (0.34-0.70) and 0.54 (0.36-0.79) for, respectively, CSM and OCM, all favoring RP (all p 0.001).RP may hold a CSM advantage over RT in cN1 PCa patients.

Introduction: Over the last decade, multiple clinical trials demonstrated improved survival after chemotherapy for metastatic prostate cancer (mPCa). However, real-world data validating this effect within large-scale epidemiological data sets are scarce. We addressed this void. Materials and Methods: Men with de novo mPCa were identified and systemic chemotherapy status was ascertained within the Surveillance, Epidemiology, and End Results database (2004–2016). Patients were divided between historical (2004–2013) versus contemporary (2014–2016). Chemotherapy rates were plotted over time. Kaplan–Meier plots and Cox regression models with additional multivariable adjustments addressed overall and cancer-specific mortality. All tests were repeated in propensity-matched analyses. Results: Overall, 19,913 patients had de novo mPCa between 2004 and 2016. Of those, 1838 patients received chemotherapy. Of 1838 chemotherapy-exposed patients, 903 were historical, whereas 905 were contemporary. Chemotherapy rates increased from 5% to 25% over time. Median overall survival was not reached in contemporary patients versus was 24 months in historical patients (hazard ratio [HR]: 0.55, p

Background To test the effect of urological primary cancers (bladder, kidney, testis, upper tract, penile, urethral) on overall mortality (OM) after secondary prostate cancer (PCa). Methods Within the Surveillance, Epidemiology and End Results (SEER) database, patients with urological primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion with primary PCa controls. OM was compared between secondary and primary PCa patients and stratified according to primary urological cancer type, as well as to time interval between primary urological cancer versus secondary PCa diagnoses. Results We identified 5,987 patients with primary urological and secondary PCa (bladder, n = 3,287; kidney, n = 2,127; testis, n = 391; upper tract, n = 125; penile, n = 47; urethral, n = 10) versus 531,732 primary PCa patients. Except for small proportions of Gleason grade group and age at diagnosis, PCa characteristics between secondary and primary PCa were comparable. Conversely, proportions of secondary PCa patients which received radical prostatectomy were smaller (29.0 vs. 33.5%), while no local treatment rates were higher (34.2 vs. 26.3%). After 1:4 matching, secondary PCa patients exhibited worse OM than primary PCa patients, except for primary testis cancer. Here, no OM differences were recorded. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis. Conclusions After detailed matching for PCa characteristics, secondary PCa patients exhibit worse survival, except for testis cancer patients. The survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary urological cancer diagnosis.

Recently, an increase in the rates of high-risk prostate cancer (PCa) was reported. We tested whether the rates of and low, intermediate, high and very high-risk PCa changed over time. We also tested whether the number of prostate biopsy cores contributed to changes rates over time.Within the Surveillance, Epidemiology and End Results (SEER) database (2010-2015), annual rates of low, intermediate, high-risk according to traditional National Comprehensive Cancer Network (NCCN) and high versus very high-risk PCa according to Johns Hopkins classification were tabulated without and with adjustment for the number of prostate biopsy cores.In 119,574 eligible prostate cancer patients, the rates of NCCN low, intermediate, and high-risk PCa were, respectively, 29.7%, 47.8%, and 22.5%. Of high-risk patients, 39.6% and 60.4% fulfilled high and very high-risk criteria. Without adjustment for number of prostate biopsy cores, the estimated annual percentage changes (EAPC) for low, intermediate, high and very high-risk were respectively -5.5% (32.4%-24.9%, p .01), +0.5% (47.6%-48.4%, p = .09), +4.1% (8.2%-9.9%, p .01), and +8.9% (11.8%-16.9%, p .01), between 2010 and 2015. After adjustment for number of prostate biopsy cores, differences in rates over time disappeared and ranged from 29.8%-29.7% for low risk, 47.9%-47.9% for intermediate risk, 8.9%-9.0% for high-risk, and 13.6%-13.6% for very high-risk PCa (all p .05).The rates of high and very high-risk PCa are strongly associated with the number of prostate biopsy cores, that in turn may be driven by broader use magnetic resonance imaging (MRI).

Objective: To assess the relationship between the volume of the index lesion (IL) measured at multiparametric magnetic resonance imaging (mpMRI; MRIvol) and at radical prostatectomy (RPvol), stratifying it according to Prostate Imaging-Reporting and Data System (PI-RADS) score. Patients and Methods: We identified 332 men with a positive mpMRI (single lesion with PI-RADS ≥3) who underwent systematic plus targeted biopsy and subsequent RP at two tertiary referral centres between 2013 and 2018. All mpMRIs were reviewed by experienced radiologists using PI-RADS scores. The study outcome was to assess the relationship between MRIvol (based on planimetry from MRI sequence best showing tumour) and RPvol (based on tumour involved area of each RP pathology slice). To achieve this endpoint, we performed a multivariable linear regression analysis (LRA) to predict RPvol using PI-RADS, prostate-specific antigen level, prostate volume, age, digital rectal examination, Gleason score at MRI-targeted biopsy, biopsy history and time from mpMRI to RP as covariates. Non-parametric locally estimated scatterplot smoothing (LOESS) function was used to graphically explore the relationship between MRIvol and RPvol, stratifying for PI-RADS score. Results: Overall, 24%, 49% and 27% of men had visible PI-RADS 3, 4 and 5 lesions at mpMRI. The median (interquartile range [IQR]) MRIvol and RPvol were 0.67(0.29–1.76)mL and 1.39(0.58–4.23)mL. At LRA, MRIvol was significantly correlated with a RPvol underestimation (slope: 2.4, 95% confidence interval [CI] 0.1–46.3). The non-parametric LOESS analysis showed a non-linear relationship between MRIvol and RPvol. Significant underestimation was reported across all volumes with the highest differences between MRIvol and RPvol in the low volume range (

Objective To understand the barriers and facilitators to single instillation of intravesical chemotherapy (SI-IVC) use following resection of non-muscle-invasive bladder cancer (NMIBC) in Scotland and England using a behavioural theory-informed approach. Materials and methods In a cross-sectional descriptive study of practices at seven hospitals, we investigated care pathways, policies, and interviewed 30 urology staff responsible for SI-IVC. We used the Theoretical Domains Framework (TDF) to organise our investigation and conducted deductive thematic analyses, while inductively coding emergent beliefs. Results Barriers to SI-IVC were present at different organisational levels and professional roles. In four hospitals there was a policy to not instil SI-IVC in theatre. Six hospitals' staff reported delays in MMC ordering and/or local storage. Lack of training, skills and perceived workload affected motivation. Facilitators included access to modern instilling devices (four hospitals) and incorporating reminders operation pro-forma (four hospitals). Performance targets (with audit and feedback) within a national governance framework was present in Scotland but not England. Differences in coordinated leadership, sharing best practices, and disliking being perceived as underperforming, were evident in Scotland. Conclusions High-certainty evidence shows that SI-IVC such as Mitomycin C (MMC), following NMIBC resection reduces recurrences. This evidence underpins international guidance. Numbers of eligible patients receiving SI-IVC is variable indicating suboptimal practice. Improving SI-IVC adherence requires modifications to theatre instilling policies, delivery and storage of MMC, staff training, and documentation. Centralising care with bladder cancer expert leadership and best practices sharing, with performance targets, likely led to improvements in Scotland. National quality improvement, incorporating audit and feedback, with additional implementation strategies targeted to professional role could improve adherence and patient outcomes elsewhere. This process should be controlled to clarify implementation intervention effectiveness.

The use of pembrolizumab has been largely accepted in several advanced types of cancers. PURE 01 study (NCT02736266) enrolled consecutively 143 patients with muscle-invasive bladder cancer who received 3 cycles of pembrolizumab 200 mg every 3 weeks before planned radical cystectomy (RC). Clinical, pathological and laboratory data were collected to investigate the relationship between renal function, immunotherapy and cancer-related outcomes. Serum creatinine and estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-equation 2009 were reported at baseline and after every cycle of pembrolizumab; the T stage from clinical classification TNM (cTNM) was stated before the treatment. Our analysis did not demonstrate a significant impairment of eGFR after any cycle of pembrolizumab, neither in the overall cohort nor in subgroups considering the T stages or the CKD G-categories according to K-DIGO 2012 classification. In conclusion, in neoadjuvant setting before RC our results suggest that pembrolizumab administration is safe for renal function preservation.

Objectives To develop and externally validate a risk calculator for prediction of any cancer recurrence in patients with penile squamous cell carcinoma (pSCC) and inguinal lymph node metastases (ILNM), as to date no validated prognostic tool is available for patients with pSCC and ILNM. Patients and methods The development cohort included 234 patients from seven referral centres. The external validation cohort included 273 patients from two additional referral centres. Cox regression identified predictors of any recurrence, which were used to develop a risk calculator. The risk-calculator grouped the development and the validation cohorts according to the individual risk of any recurrence at 24 months (24m-R). Adjuvant treatment effects were tested on overall survival (OS) according to the derived tertiles, within the development and validation cohorts. Results Positive surgical margins, pN3 , and ILNM ratio were associated with higher recurrence rate. The 2-year OS rates were lower for patients with high (>37%) and intermediate (19-37%) compared to low ( 0.1). Conclusion Adjuvant treatment planning is crucial in patients with pSCC with ILNM, where only weak evidence is available. The current tool proved to successfully stratify patients according to their individual risk, potentially allowing better tailoring of adjuvant treatments.

Background and Objectives: To investigate other-cause mortality (OCM) rates over time according to several baseline characteristics in bladder cancer (BCa) patients treated with radical cystectomy (RC). Methods: Within the Surveillance, Epidemiology, and End Results database (1988-2011), we identified 7702 T1-2N0M0 urothelial BCa patients treated with RC. Temporal trends and multivariable Cox regression (MCR) analyses assessed 5-year OCM. Data were stratified according to the year of diagnosis (1988-1995 vs 1996-2000 vs 2001-2004 vs 2005-2008 vs 2009-2011), age group (75 years), sex, race, marital status, and socioeconomic status. Results: Overall, OCM rates decreased from 13.9% in 1988-1995 to 8.6% in 2009-2011. The greatest decrease was recorded in elderly (>75) patients (32%-16%, slope: −0.55% per year; P =.01), followed by patients aged 60 to 75 (21%-5%, slope: −0.35% per year; P =.01), unmarried patients (16%-10%, slope: −0.26% per year; P

Objectives To identify predictors of poor overall survival (OS) amongst patients with penile squamous cell carcinoma (pSCC) with clinical inguinal lymphadenopathy (cN+), in order to define the best candidates for neoadjuvant chemotherapy (NAC). Patients and methods Using an international, multicentre database of 924 patients with pSCC, we identified 334 men who harboured cN+ with available clinical and follow-up data. Lymph node involvement was defined either by the presence of palpable inguinal node disease or by preoperative computed tomography (CT) assessment. Fluorine-18 fluorodeoxyglucose positron-emission tomography (18 F-FDG-PET)/CT scan was performed based on clinical judgment of the treating physician. Regression-tree analysis generated a risk stratification tool for prediction of 24-month overall mortality (OM). Kaplan-Meier explored the OS benefit related to the use of NAC according to the regression-tree-stratified subgroups. Results Overall, 120 (35.9%), 152 (45.5%), and 62 (18.6%) patients harboured cN1, cN2, and cN3 disease. 18 F-FDG-PET/CT was performed in 48 (14.4%) patients, and 16 (4.8%) had inguinal and pelvic nodal PET detection. The median OS was 107 months, with a 24-month OS of 66%. At regression-tree analysis (area under the curve = 70%), patients with cN3 and cN2 with PET/CT-detected inguinal and pelvic nodal activity had a higher risk of 24-month OM (>50%). NAC was associated with improved 24-month OS rates (54% vs 33%) only in this subgroup of patients (P = 0.002), which was also confirmed after multivariable adjustment (hazard ratio 0.28, 95% confidence interval 0.13-0.62; P = 0.002). Conclusion Patients with pSCC with cN3 or cN2 and inguinal and pelvic 18F-FDG-PET/CT scan detected disease had higher 24-month OM rates according to our regression-tree model. NAC was associated with improved OS only in these subgroups of patients. Our novel decision model may help to stratify cN+ patients, and identify those who most likely will benefit from NAC prior to radical surgical resection.

Objectives: To analyze contemporary multimodality treatment rates, defined as radical cystectomy plus chemotherapy and/or radiotherapy, for pT2–3 any N-stage M0 non-urothelial carcinoma of urinary bladder patients. Additionally, we tested for the effect of multimodality treatment versus radical cystectomy alone on cancer-specific mortality. Methods: Within the Surveillance, Epidemiology and End Results database (2004–2015), 887 pT2–3 any N-stage M0 non-urothelial carcinoma of urinary bladder patients treated with radical cystectomy were identified. Kaplan–Meier plots, and univariable and multivariable Cox regression analyses focused on cancer-specific mortality rates. Results: Squamous cell carcinoma was recorded in 499 (56.3%) patients, neuroendocrine carcinoma in 246 (27.7%) and adenocarcinoma in 142 (16.0%). The highest proportion of multimodality treatment patients was recorded in neuroendocrine carcinoma (69.1%), relative to adenocarcinoma (34.5%) and squamous cell carcinoma (26.4%). A statistically significant annual increase was recorded in multimodality treatment rates in neuroendocrine carcinoma patients (46.7–74.2%, P&nbsp

Background and objectives To examine the effect of conditional survival on 5-year cancer-specific survival (CSS) probability after radical nephroureterectomy (RNU) in a contemporary cohort of patients with non-metastatic urothelial carcinoma of the upper urinary tract (UTUC). Methods Within the Surveillance, Epidemiology and End Results database (2004-2015), 6826 patients were identified. Conditional 5-year CSS estimates were assessed after event-free follow-up duration. Multivariable Cox regression (MCR) models predicted cancer-specific mortality (CSM) according to event-free follow-up length. Results Overall, 956 (14.0%) were T1 low grade(LG)N0 , 1305 (19.1%) T1 high grade(HG)N0 , 1215 (17.8%) T2 N0 , 2249 (32.9%) T3 N0 and 1101 (16.1%) T4 N0 /Tany N1-3 . From baseline, 93.4% to 94.2% in T1 LGN0 provided 5-year CSS and, respectively, 86.2% to 95.3% in T1 HGN0 , 77.5% to 87.8% in T2 N0 , 63.0% to 91.1% in T3 N0 , and 38.8% to 88.2% in T4 N0 /Tany N1-3 . In MCR models, relative to T1 LGN0 , T1 HGN0 (Hazard ratio [HR] 1.7), T2 N0 (HR 3.0), T3 N0 (HR: 5.2), and T4 N0 /Tany N1-3 (HR 11.9) were independent predictors of higher CSM. Conditional HRs decreased to levels equivalent to T1 LGN0 at 3 years vs 5 years of event-free survival for T1 HGN0 and all other groups, respectively. Conclusions A direct relationship exists between event-free follow-up and survival probability after RNU. From a clinical perspective, such survival estimates may have particular importance during preoperative counseling.

Background: To investigate the effect of frailty on short-term postoperative outcomes and total hospital charges (THCs) in patients with non-metastatic upper urinary tract carcinoma, treated with radical nephroureterectomy (RNU). Methods: Within the National Inpatient Sample (NIS) database we identified 11 258 RNU patients (2000-2015). We used the Johns Hopkins frailty-indicator to stratify patients according to frailty status. Time trends and multivariable logistic, Poisson and linear regression models were applied. Results: Overall, 1801 (16.0%) patients were frail, 4664 (41.4%) were older than 75 years and 1530 (13.6%) had Charlson comorbidity index ≥2. Rates of frail patients increased over time, from 7.3% to 24.9% (P

Background: the pathological stage of prostate cancer with high-risk prostate-specific antigen (PSA) levels, but otherwise favorable and/or intermediate risk characteristics (clinical T-stage, Gleason Grade group at biopsy [B-GGG]) is unknown. We hypothesized that a considerable proportion of such patients will exhibit clinically meaningful GGG upgrading or non-organ confined (NOC) stage at radical prostatectomy (RP). Materials and methods: within the Surveillance, Epidemiology, and End Results: database (2010-2015) we identified RP-patients with cT1c-stage and B-GGG1, B-GGG2, or B-GGG3 and PSA 20-50 ng/ml. Rates of GGG4 or GGG5 and/or rates of NOC stage (>= pT3 and/or pN1) were analyzed. Subsequently, separate univariable and multivariable logistic regression models tested for predictors of NOC stage and upgrading at RP. Results Of 486 assessable patients, 134 (28%) exhibited B-GGG1, 209 (43%) B-GGG2, and 143 (29%) B-GGG3, respectively. The overall upgrading and NOC rates were 11% and 51% for a combined rate of upgrading and/or NOC stage of 53%. In multivariable logistic regression models predicting upgrading, only B-GGG3 was an independent predictor (odds ratio [OR]: 5.29; 95% confidence interval [CI]: 2.21-14.19; p < 0.001). Conversely, 33%-66% (OR: 2.36; 95% CI: 1.42-3.95; p = 0.001) and >66% of positive biopsy cores (OR: 4.85; 95% CI: 2.84-8.42; p < 0.001), as well as B-GGG2 and B-GGG3 were independent predictors for NOC stage (all p, Stiftung Giersch; Projekt DEAL

OBJECTIVE To examine the incidence and time trends of secondary bladder cancer (BCa) and rectal cancer (RCa) after brachytherapy (BT) relative to radical prostatectomy (RP). MATERIALS AND METHODS Within the Surveillance, Epidemiology and End Results (SEER) database (1988-2015), we identified patients with localized PCa as an only or first primary cancer, who underwent BT or RP. Cumulative incidence plots and multivariable competing-risks regression (CRR) models were used. Sensitivity analyses focused on patients' age and year of diagnosis intervals and tested the effect of an unmeasured confounder. RESULTS Of 318 058 patients with localized prostate cancer (PCa), 55 566 (18.4%) underwent BT. After propensity score-matching, 20-year secondary BCa incidence was 6.0% in patients who had undergone BT vs 2.4% in those who had undergone RP (P CONCLUSIONS: Brachytherapy predominantly increases the risk of secondary BCa and, to a lesser extent, that of RCa. Follow-up of such patients is therefore required. It is encouraging that both secondary BCa, and RCa rates, in particular, have recently decreased, RCa.

Objectives: To examine intraoperative and postoperative morbidity and mortality, as well as the impact on length of stay and total hospital charges of minimally invasive nephroureterectomy compared with open nephroureterectomy in patients with upper tract urothelial carcinoma. Methods: Within the National Inpatient Sample (2008–2013), we identified patients with non-metastatic upper tract urothelial carcinoma treated with either minimally invasive nephroureterectomy or open nephroureterectomy. We relied on inverse probability of treatment weighting to reduce the effect of inherent differences between open nephroureterectomy versus minimally invasive nephroureterectomy. Multivariable logistic regression, multivariable Poisson regression models and multivariable linear regression models were used. Results: Between 2008 and 2013, we identified 3897 patients treated with either minimally invasive nephroureterectomy (1093 [28%]) or open nephroureterectomy (2804 [72%]). In multivariable logistic regression models, minimally invasive nephroureterectomy resulted in lower rates of overall (odds ratio 0.71, P&nbsp

Objectives To create a model that predicts side-specific seminal vesicle invasion using clinical, biopsy and multiparametric magnetic resonance imaging data. Methods We analyzed data from 544 patients who underwent robot-assisted radical prostatectomy at a single institution. To develop a side-specific predictive model, we ultimately considered four variables: prostate-specific antigen, highest ipsilateral biopsy Gleason grade, highest ipsilateral percentage core involvement and seminal vesicle invasion on multiparametric magnetic resonance imaging. A binary multivariable logistic regression model was fitted to predict seminal vesicle invasion. A nomogram was then built based on the coefficients of the resulting logit function. The leave-one-out cross validation method was used for internal validation, and the decision curve analysis for the evaluation of the net clinical benefit. Results We relied on 804 side-specific cases after excluding negative biopsy observations (n = 284). Seminal vesicle invasion was reported on multiparametric magnetic resonance imaging in 41 (5%) cases, and on final pathology in 64 (8%) cases. All variables in the model emerged as predictors of seminal vesicle invasion (all P ≤ 0.001) and were subsequently considered to build a nomogram. The area under the curve of multiparametric magnetic resonance imaging alone in predicting seminal vesicle invasion was 59.1%; whereas one of the clinical variables only was 85.1%. The area under the curve of the nomogram resulting from their combination was 86.5%. After internal validation, this resulted in 84.7%. The model achieved good calibration and the decision curve analysis showed its clinical benefit, especially when compared with relying only on multiparametric magnetic resonance imaging prediction of seminal vesicle invasion. Conclusions A nomogram based on clinical and multiparametric magnetic resonance imaging data can predict seminal vesicle invasion and serve as a tool to urologists for surgical planning.

BACKGROUND To test whether local treatment (LT), namely radical prostatectomy (RP) or brachytherapy (BT) still confers a survival benefit versus no local treatment (NLT), when adjusted for baseline PSA (bPSA). To further examine whether the effect of LT might be modulated according to bPSA and M1 substages. METHODS Of 13 906 mPCa patients within the SEER (2004-2014), 375 underwent RP, 175 BT, and 13 356 NLT. Multivariable competing risks regression (MVA CRR) analyses after 1:2 propensity score matching assessed the impact of LT versus NLT on cancer specific mortality (CSM). Interaction analyses tested the association between treatment type and bPSA within different M1 substages. RESULTS MVA CRR analyses revealed lower CSM rates for LT (RP [HR: 0.55, CI: 0.44-0.70, P

Purpose: To assess the effect of pelvic lymph node dissection (PLND) extent on cancer-specific mortality (CSM) in prostate cancer (PCa) patients without lymph node invasion (LNI) treated with radical prostatectomy (RP). Methods: Within the Surveillance, Epidemiology, and End results (SEER) database (2004-2014), we identified patients with D'Amico intermediate- or high-risk characteristics who underwent RP with PLND, without evidence of LNI. First, multivariable logistic regression models tested for predictors of more extensive PLND, defined as removed lymph node count (NRN) ≥75th percentile. Second, Kaplan-Meier analyses and multivariable Cox regression models tested the effect of NRN ≥75th percentile on CSM. Finally, survival analyses were repeated using continuously coded NRN. Results: In 28147 RP and PLND patients without LNI, 67.3% versus 32.7% exhibited D'Amico intermediate- or high-risk characteristics. The median NRN was 6 (IQR 3-10), the 75th percentile defined patients with NRN ≥11. Patients with NRN ≥11 had higher rate of cT2/3 stage (29.8 vs 26.1%), GS ≥8 (25.7 vs 22.4%), and respectively more frequently exhibited D'Amico high-risk characteristics (34.6 vs 32.1%). In multivariable logistic regression models predicting the probability of more extensive PLND (NRN ≥11), higher biopsy GS, higher cT stage, higher PSA, more recent year of diagnosis, and younger age at diagnosis represented independent predictors. At 72 months after RP, CSM-free rates were 99.5 versus 98.1% for NRN ≥11 and NRN ≤10, respectively and resulted in a HR of 0.50 (P=0.01), after adjustment for all covariates. Similarly, continuously coded NRN achieved independent predictor status (HR: 0.955, P=0.01), where each additional removed lymph node reduced CSM risk by 4.5%. Conclusion: More extensive PLND at RP provides improved staging information and consequently is associated with lower CSM in D'Amico intermediate- and high-risk PCa patients without evidence of LNI. Hence, more extensive PLND should be recommended in such individuals.

Neglected side effects after radical prostatectomy have been previously reported. In this context, the prevalence of penile morphometric alterations has never been assessed in robot-assisted radical prostatectomy series. We aimed to assess prevalence of and predictors of penile morphometric alterations (i.e. penile shortening or penile morphometric deformation) at long-term follow-up in patients submitted to either robot-assisted (robot-assisted radical prostatectomy) or open radical prostatectomy. Sexually active patients after either robot-assisted radical prostatectomy or open radical prostatectomy prospectively completed a 28-item questionnaire, with sensitive issues regarding sexual function, namely orgasmic functioning, climacturia and changes in morphometric characteristics of the penis. Only patients with a post-operative follow-up ≥ 24 months were included. Patients submitted to either adjuvant or salvage therapies or those who refused to comprehensively complete the questionnaire were excluded from the analyses. A propensity-score matching analysis was implemented to control for baseline differences between groups. Logistic regression models tested potential predictors of penile morphometric alterations at long-term post-operative follow-up. Overall, 67 (50%) and 67 (50%) patients were included after open radical prostatectomy or robot-assisted radical prostatectomy, respectively. Self-rated post-operative penile shortening and penile morphometric deformation were reported by 75 (56%) and 29 (22.8%) patients, respectively. Rates of penile shortening and penile morphometric deformation were not different after open radical prostatectomy and robot-assisted radical prostatectomy [all p > 0.5]. At univariable analysis, self-reported penile morphometric alterations (either penile shortening or penile morphometric deformation) were significantly associated with baseline international index of erectile function–erectile function scores, body mass index, post-operative erectile function recovery, year of surgery and type of surgery (all pÂ

We read with interest the article by Franklin et al.(1) discussing the predictive value of 3T multiparametric MRI and PSMA PET/CT scan for pathological outcomes at radical prostatectomy and pelvic lymph node dissection (PLND) for prostate cancer (PCa), recently published in the British Journal of Urology International. We all recognize that both multiparametric MRI (mpMRI) and PSMA PET/CT have been progressively gaining space in the diagnosis and staging of PCa and we expect that the diffusion of these exciting modalities will skyrocket up over time.

OBJECTIVE To assess the effect of lymph node dissection (LND), number of removed nodes (NRN), and number of positive nodes (NPN), on cancer-specific mortality (CSM) in contemporary vs historical patients with pT2-3 Nany M0 renal cell carcinoma (RCC) treated with radical nephrectomy (RN). PATIENTS AND METHODS Within the Surveillance, Epidemiology, and End Results database (2001-2013), we identified patients with non-metastatic pT2-3 Nany RCC who underwent RN with or without LND. Kaplan-Meier analyses and multivariable Cox regression models with propensity score weighting for inverse probability of treatment were used. RESULTS Of 25 357 patients, 24.8% underwent LND (2001-2007: 3 167 patients vs 2008-2013: 3 133 patients). The median NRN was 3 (interquartile range [IQR]: 1-7). Positive nodes were identified in 17.1%: 9.3% of pT2 and 21.6% of pT3 patients, who underwent LND. The median NPN was 2 (IQR: 1-3). In multivariable models, LND did not decrease CSM (hazard ratio [HR] 1.29; P < 0.001). LND extent, defined as NRN, did not decrease CSM (HR 0.94; P = 0.3). Finally, multivariable models testing the effect of NPN showed increased CSM in pT3 but not in pT2 patients (HR 1.29 and 1.58, P = 0.02 and P = 0.1, respectively). NRN exerted a protective effect on CSM in patients with positive nodes (HR 0.98; P = 0.007). CONCLUSION In contemporary and historical patients LND or its extent do not protect from CSM. However, the NPN increases the rate of CSM in pT3 patients. Consequently, LND and its extent appear to have little if any therapeutic value in pT2-3 Nany M0 patients, besides its prognostic impact. High-risk non-metastatic patients may represent a target population for a multi-institutional prospective trial.

Objective: To analyse the outcomes of adjuvant chemotherapy vs observation in a multicentre cohort of patients with upper tract urothelial carcinoma (UTUC) in order to clarify whether such patients benefit from adjuvant chemotherapy after radical nephroureterectomy (RNU). Patients and Methods: Data from 15 centres were collected for a total of 1544 patients, treated between 2000 and 2015. Criteria for patient selection included pT2–4N0/x stage, or lymph node-positive disease, and prior RNU. The standardized difference approach was used to compare subgroup characteristics. Overall survival (OS) was the primary endpoint. The primary analysis used 1:1 propensity score matching, with inverse probability of treatment weighting in addition to this in the secondary analysis. The latter was also performed with the inclusion of covariates, i.e. with ‘doubly robust’ estimation. A 6-month landmark analysis was performed to exclude early events. Results: A total of 312 patients received adjuvant chemotherapy and 1232 underwent observation. Despite differences between the two groups, the standardized difference was generally

OBJECTIVE: To establish an external validation of the new nomogram from Gandaglia et al which provides estimates of the probability of pathological favorable disease in pre-operatively defined intermediate-risk PCa. PATIENTS AND METHODS: Overall, 2928 intermediate-risk PCa patients according to the D'Amico classification undergoing RP and bilateral lymph node dissection in seven academic centres between 2000 and 2011. Pathologically favorable PCa was defined as low-grade organ-confined disease. The Receiver Operating Characteristic (ROC) curve was obtained to quantify the overall accuracy (Area Under the Curve, AUC) of the model to predict specimen-confined (SC) disease. Calibration curve was then constructed to illustrate the relationship between the risk-estimates obtained by the model and the observed proportion of SC disease. Kaplan-Meier method was used for PSA recurrence-free survival (PSA-RFS) assessment. RESULTS: Median age was 68 years. 10.6% patients finally presented pathologically favorable disease characteristics at RP. A higher PSAD (OR = 0.01; 95%CI = 0.00-0.04; P < 0.0001) and percentage of positive cores (OR = 0.97; 95%CI = 0.96-0.98; P < 0.0001) were associated with a reduced probability of favorable disease at RP in multivariate analysis. ROC curve analysis showed strongest accuracy of the model (AUC = 0.82; 95%CI = 0.79-0.84). Favorable PCa had a significantly better PSA recurrence-free survival rates as compared to unfavorable PCa after RP (94.2% vs 74.4% at 4 years, P < 0.0001). CONCLUSIONS: This external validation of the Gandaglia nomogram shows relevant accuracy with one out of ten patients in this intermediate risk PCa group with pathologically proven organ-confined disease. This validated risk calculator can help physician to distinguish favorable intermediate risk PCa that can be treated by conservative approach or safer nerve-sparing surgery.

BACKGROUND. National Comprehensive Cancer Network (NCCN) guidelines recommend a pelvic lymph node dissection (PLND) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) if a nomogram predicted risk of lymph node invasion (LNI) is ≥2%. We examined this and other thresholds, including nomogram validation. METHODS. We examined records of 26,713 patients treated with RP and PLND between 2010 and 2013, within the Surveillance, Epidemiology, and End Results database. Nomogram thresholds of 2–5% were tested and external validation was performed. RESULTS. LNI was recorded in 4.7% of patients. Nomogram accuracy was 80.4% and maintained minimum accuracy of 75.6% in subgroup analyses, according to age, race, and nodal yield >10. With the NCCN recommended 2% nomogram threshold, PLND could be avoided in 22.3% of patients at the expense of missing 3.0% of individuals with LNI. Alternative thresholds of 3%, 4%, and 5% yielded respective PLND avoidance rates of 60.4%, 71.0%, and 79.8% at the expense of missing 17.8%, 27.2%, and 36.6% of patients with LNI. NCCN cut-off recommendation was best satisfied with a threshold of

Germ cell tumors (GCT), accounting for 95% of malignant testicular tumors, can be divided into two groups: seminoma (SGCT) and non-seminoma (NSGCT). Seminomas typically arise in men in the fourth decade of life, compromising 60% of the GCT. At diagnosis, approximately 75% present with local disease (Stage I); 15% is detected with metastatic regional lymph nodes (Stage II) and 5-10% present with juxtaregional or visceral metastasis (Stage III) . This article is protected by copyright. All rights reserved. ispartof: BJU INTERNATIONAL vol:124 issue:1 pages:35-39 ispartof: location:England status: published

BACKGROUND Controversial results have shown a significant association with either low or high total testosterone (tT) levels and high risk prostate cancer (PCa). We tested the relationship between circulating tT and grade group 5 (G5) PCa at radical prostatectomy (RP) in patients with preoperative low- to intermediate-risk disease. METHODS Serum sex hormones were assessed the day before RP in a cohort of 846 patients with low- to intermediate-risk PCa. Patients were segregated using the new 5-tiered Gleason grade groups. Restricted cubic spline functions and logistic regression analyses tested the association between sex hormones and G5 PCa. Differences in potential predictive accuracy (PA) were assessed for tT and prostate-specific antigen (PSA) levels. RESULTS Overall, 27 men (3.2%) had G5 PCa at RP, and this group had higher PSA values than patients with G1-G4 PCa (P = 0.02). The groups did not differ in terms of preoperative mean hormonal values. Both low and high circulating tT values depicted a nonlinear U-shaped correlation with G5 PCa at RP. The lowest and highest (10th and 90th percentiles) tT values and biopsy PCa grade emerged as multivariable independent predictors of G5 PCa at RP (all P

BACKGROUND A new prostate cancer (PCa) grading system (namely, Gleason score-GS- ≤6 vs. 3 + 4 vs. 4 + 3 vs. 8 vs. ≥9) was recently proposed and assessed on biochemical recurrence (BCR) showing improved predictive abilities compared to the commonly used three-tier system (GS ≤6 vs. 7 vs. ≥8). We assessed the predictive ability of the five-tier grade group (GG) system on harder clinical endpoint, namely clinical recurrence (CR). METHODS Between 2005 and 2014, 9,728 clinically localized PCa patients were treated with radical prostatectomy (RP) at two tertiary referral centers. Kaplan–Meier curves, multivariable Cox regression analyses, and concordance index (C-index) were used to assess CR after treatment according to four Gleason grade classifications at biopsy and RP: Group 1: ≤6 versus 7 versus ≥8; Group 2: ≤6 versus 3 + 4 vs. 4 + 3 versus ≥8; Group 3: ≤6 versus 7 versus 8 versus ≥9; Group 4: ≤6 versus 3 + 4 versus 4 + 3 versus 8 versus ≥9. Same analyses were repeated in patients who had BCR (n = 1,624). Decision curve analyses were performed to evaluate and compare the net benefit associated with the use of the four Gleason grade classifications. RESULTS Overall, 443 (4.6%) patients had CR. The hazard ratio of the GS 3 + 4, 4 + 3, 8, and ≥9 relative to GS ≤6 were 3.63, 5.93, 11.44, 18.08 and 4.93, 9.99, 15.31 and 25.12 in the pre- and post-treatment models, respectively. The C-index of the five-tier GG system was slightly higher relative to the other 3 Gleason grade classifications both in the pre- (range: 0.001–0.006) and post-treatment models (range: 0–0.008). Similar findings were observed when we focused our analyses in patients with BCR after RP. The use of the five-tier GG system did not result into higher net-benefit relative to the other three Gleason grade classifications. CONCLUSIONS The difference in accuracy between the five-tier GG system and the other Gleason grade classifications, using CR as an endpoint, is clinically negligible. Current evidence suggests that the five-tier GG system represents a simplified user-friendly scheme available for patient counseling rather than a new histopathological diagnostic system that improves the prediction of CR. Prostate © 2016 Wiley Periodicals, Inc.

Objective To externally validate the updated 2012 Partin Tables in contemporary North American patients treated with radical prostatectomy (RP) for localized prostate cancer (PCa) at community institutions. Materials and methods We examined records of 25,254 patients treated with RP and pelvic lymph node dissection (PLND) between 2010 and 2013, within the surveillance, epidemiology, and end results database. The ROC derived AUC assessed discriminant properties of the updated 2012 Partin Tables of organ confined disease (OC), extracapsular extension (ECE), seminal vesical invasion (SVI), and lymph node invasion (LNI). Calibration plots focused on calibration between predicted and observed rates. Results Proportions of OC, ECE, SVI, and LNI at RP were 69.8%, 18.4%, 7.4%, and 4.4%, respectively. Accuracy for prediction of OC, ECE, SVI, and LNI was 70.4%, 59.9%, 72.9%, and 77.1%, respectively. In subgroup analyses in patients with nodal yield >10, accuracy for LNI prediction was 76.0%. Subgroup analyses in elderly patients and in African American patients revealed decreased accuracy for prediction of all four endpoints. Last but not least, SVI and LNI calibration plots showed excellent agreement, versus good agreement for OC (maximum underestimation of 10%) and poor agreement for ECE (maximum overestimation of 12%). Conclusion Taken together, the updated 2012 Partin Tables can be unequivocally endorsed for prediction of OC, SVI, and LNI in community-based patients with localized PCa. Conversely, ECE predictions failed to reach the minimum accuracy requirements of 70%. Prostate 77:105-113, 2017. © 2016 Wiley Periodicals, Inc.

INTRODUCTION To identify the most significant cut-off of tumor volume (TV) for prediction of clinical failure (CF) among high-risk prostate cancer (hPCa) patients. METHODS Within a multi-institutional cohort, 262 patients treated with radical prostatectomy (RP) for hPCa were identified. CF was defined as local recurrence or distant metastases. A time dependent ROC curve was used to evaluate the area under the curve (AUC) using TV as single marker to predict clinical failure at 10 years. We searched for the TV cut off value with the highest combined sensitivity and specificity predicting CF. Three multivariable Cox regression analyses (MVA) tested the predictors of CF after RP. Predictors of the model 1 were pre-operative PSA, pathologic stage (PT), pathologic Gleason sum (GS), surgical margin status, and lymph node invasion. Predictors of the models 2 and 3 were the same of model 1 plus TV as a continuous or dichotomous variable using the defined cutoff, respectively. Validation (leave-one-out-cross-validation-LOOCV) of each model was performed. RESULTS Overall, 46 (17.6%) patients experienced CF. The TV value was 6.29 ml. In MVA of models 2 and 3, PT and GS remained independent predictors of CF. Moreover, in model 2 TV (HR:1.07,) and in model 3 TV >6.29 ml (HR:2.99,) were independently associated with CF. In LOOCV, the C-index of models 1–3 were 65.53%, 71.75%, and 70.26%, respectively. CONCLUSIONS TV is an independent predictor of CF in hPCa patients. Patients with a TV exceeding the cut-off of 6.29 ml are more likely to develop CF. Prostate © 2016 Wiley Periodicals, Inc.

Objectives To examine, using competing risks regression, differences in cancer-specific mortality (CSM) that might distinguish between local tumour ablation (LTA) and observation (OBS) for patients with kidney cancer. Patients and Methods The study focused on 1 860 patients with cT1a kidney cancer treated with either LTA or OBS between 2000 and 2009 in the Surveillance Epidemiology and End Results-Medicare database. Propensity-score matching was used. The study outcome was CSM. Multivariable competing risks regression analyses, adjusting for other-cause mortality as well as patient (including comorbidities) and tumour characteristics, were fitted. Results Overall, fewer patients underwent LTA than OBS (30 vs 70%; n = 553 vs n = 1 307). Compared with patients in the OBS group, those in the LTA group were younger (median age 77 vs 78 years; P < 0.001), more likely to be white (84 vs 78%; P = 0.005), more frequently married (59 vs 52%; P = 0.02) and more frequently of high socio-economic status (54 vs 45%; P = 0.001). After propensity-score matching, 553 patients who underwent LTA and 553 who underwent OBS remained for subsequent analyses. The mean standardized differences of patient characteristics between the two groups were

Objective To validate Caveolin-1 as an independent prognostic marker of biochemical recurrence (BCR) in a large multi-institutional cohort of patients with prostate cancer treated with radical prostatectomy (RP). Patients and Methods Caveolin-1 expression was evaluated by immunochemistry on a tissue microarray in 3 117 patients treated with RP for prostate cancer at five institutions. Univariable and multivariable Cox proportional hazards regression models assessed the association of Caveolin-1 status with BCR. Harrell's c-index quantified prognostic accuracy. Results Caveolin-1 was overexpressed in 644 (20.6%) patients and was associated with higher pathological Gleason sum (P = 0.002) and lymph node metastases (P = 0.05). Within a median (interquartile range) follow-up of 38 (21–66) months, 617 (19.8%) patients experienced BCR. Patients with overexpression of Caveolin-1 had worse BCR-free survival than those with normal expression (log-rank test, P = 0.004). Caveolin-1 was an independent predictor of BCR in multivariable analyses that adjusted for the effects of standard clinicopathological features (hazard ratio 1.21, P = 0.037). Addition of Caveolin-1 in a model for prediction of BCR based on these standard prognosticators did not significantly improve the predictive accuracy of the model. In subgroup analyses, Caveolin-1 was associated with BCR in patients with favourable pathological features (pT2pN0 and Gleason score = 6; P = 0.021). Conclusions We confirmed that overexpression of Caveolin-1 is associated with adverse pathological features in prostate cancer and independently predicts BCR after RP, especially in patients with favourable pathological features. However, it did not add prognostically relevant information to established predictors of BCR, limiting its use in clinical practice.

Objectives: To evaluate the role of prostate volume assessed at final pathology in the risk of biochemical recurrence in patients with clinically localized prostate cancer treated with radical prostatectomy. Methods: Overall, 5637 patients treated with radical prostatectomy between January 1993 and August 2013 were identified. Multivariable Cox regression analyses tested the association between prostate volume and biochemical recurrence in the overall population and after stratifying patients according to the D’Amico risk groups. Results: Mean (median) prostate volume was 50.61mL (46mL). When patients were stratified according to D’Amico risk groups, mean (median) prostate volume was 51.7mL (48mL), 49.8mL (45mL) and 50.6mL (46mL) in low-, intermediate-, and high-risk prostate cancer, respectively (P=0.04). Overall, the 5-year biochemical recurrence-free survival rate was 87.9%. In multivariable Cox regression analyses, prostate volume was associated with a lower risk of biochemical recurrence (hazard ratio 0.99, 95% confidence interval 0.99–1.00), after accounting for disease characteristics. However, when patients were stratified according to D’Amico risk groups, prostate volume represented an independent predictor of biochemical recurrence only in individuals with intermediate-risk disease (hazard ratio 0.99, 95% confidence interval 0.99–1.00). Conversely, prostate volume was not associated with the risk of experiencing biochemical recurrence in patients with low- and high-risk disease. Conclusions: Smaller prostates are associated with increased risk of biochemical recurrence after surgery only in men with intermediate-risk disease. In this category, the preoperative assessment of prostate volume might be helpful in order to identify patients at higher risk of biochemical recurrence after surgery. Additionally, prostate volume might be used to individualize follow-up schedules after radical prostatectomy.

Objective To compare outcomes of patients with lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) treated with or without cisplatin-based combined adjuvant chemotherapy (AC) after radical cystectomy (RC). Patients and Methods We retrospectively analysed 1523 patients with LN-positive UCB, who underwent RC with bilateral pelvic LN dissection. All patients had no evidence of disease after RC. AC was administered within 3 months. Competing-risks models were applied to compare UCB-related mortality. Results Of the 1523 patients, 874 (57.4%) received AC. The cumulative 1-, 2- and 5-year UCB-related mortality rates for all patients were 16%, 36% and 56%, respectively. Administration of AC was associated with an 18% relative reduction in the risk of UCB-related death (subhazard ratio 0.82, P = 0.005). The absolute reduction in mortality was 3.5% at 5 years. The positive effect of AC was detectable in patients aged ≤70 years, in women, in pT3–4 disease, and in those with a higher LN density and lymphovascular invasion. This study is limited by its retrospective and non-randomised design, selection bias, the absence of central pathological review and lack in standardisation of LN dissection and cisplatin-based protocols. Conclusion AC seems to reduce UCB-related mortality in patients with LN-positive UCB after RC. Younger patients, women and those with high-risk features such as pT3–4 disease, a higher LN density and lymphovascular invasion appear to benefit most. Appropriately powered prospective randomised trials are necessary to confirm these findings.

Objectives To evaluate the effect of previous prostate surgery performed for lower urinary tract symptoms (LUTS) on the ability to predict lymph node invasion (LNI) in patients subsequently diagnosed with prostate cancer, testing two widely used LNI predictive models. Patients and Methods From 1990 to 2012, we collected data on 4734 patients with prostate cancer treated with radical prostatectomy and extended pelvic LN dissection (ePLND). Of these, 4453 (94%) had no prior prostate surgery (‘naive patients’), while 286 (6%) had previously undergone surgery for LUTS. Two LNI prediction models based on patients treated with ePLND were evaluated using the receiver operating characteristic-derived area under the curve (AUC), the calibration plot method, and decision-curve analyses. Results The rate of LNI was 12%, while the median number of LNs removed was 15 in both groups (P = 0.9). The two tested nomograms provided more accurate prediction in naive patients than for those previously treated with prostate surgery for LUTS (AUC: 82% and 81% vs 68% and 71%, P = 0.01 and P = 0.04, respectively). In naive patients the surgeon would have missed one LNI for every 53 and 34 avoided ePLND using the Briganti and Godoy nomograms, respectively; in patients previously treated with surgery for LUTS, a LNI would have been missed in 13 and 21 patients not undergoing ePLND. Conclusion The accuracy and the clinical net-benefit of LNI prediction tools decrease significantly in patients with prior prostate surgery for LUTS. These models should be avoided in such patients, who should undergo routine ePLND.

Aims To develop a nomogram predicting benign prostatic obstruction (BPO). Methods We included in this study 600 men with lower urinary tract symptoms (LUTS) and benign prostatic enlargement (BPE) who underwent standardized pressure flow studies (PFS) between 1996 and 2000. Complete clinical and urodynamic data were available for all patients. Variables assessed in univariate and multivariate logistic regression models consisted of IPSS, PSA, prostate size, maximal urinary flow rate (Qmax) at free flow, residual urine (RU), and bladder wall thickness (BWT). These were used to predict significant BPO (defined as a Schafer grade ≥ 3 in PFS). Results A preliminary multivariate model, including IPSS, Qmax at free flow and RU, suggested that only Qmax at free flow was a statistically significant predictor of BPO (P = 0.00) with a predictive accuracy (PA) of 82%. Further development of the multivariate model showed how the inclusion of BWT did not increase PA. Only transitional zone volume (TZV) proved to be an additional statistically significant predictor for BPO (P = 0.00). The combination of Qmax at free flow and TZV demonstrated a PA of 83.2% and were included in the final nomogram format. Conclusions We developed a clinical nomogram, which is both accurate and well calibrated, which can be helpful in the management of patients with LUTS and BPE. External validation is warranted to confirm our findings. Neurourol. Urodynam. 35:235–240, 2016. © 2014 Wiley Periodicals, Inc.

Metabolic syndrome is a cluster of several metabolic abnormalities, its prevalence is increasing worldwide. To summarize the most recent evidence regarding the relationship between metabolic syndrome, its components and the oncological outcomes in bladder cancer patients, a National Center for Biotechnology Information PubMed search for relevant articles either published or e-published up to March 2014 was carried out by combining the following Patient population, Intervention, Comparison, Outcome terms: metabolic syndrome, obesity, body mass index, hyperglycemia, insulin resistance, diabetes, hypertension, dyslipidemia, bladder cancer, risk, mortality, cancer specific survival, disease recurrence and progression. Metabolic syndrome is a complex, highly prevalent disorder, and central obesity, insulin resistance, dyslipidemia and hypertension are its main components. Published findings would suggest that metabolic syndrome per se might be associated with an increased risk of bladder cancer in male patients, but it did not seem to confer a risk of worse prognosis. Considering the primary components of metabolic syndrome (hypertension, obesity and dyslipidemia), available data are uncertain, and it is no possible to reach a conclusion yet on either a direct or an indirect association with bladder cancer risk and prognosis. Only with regard to type 2 diabetes mellitus, available data would suggest a potential negative correlation. However, as the evaluation of bladder cancer risk and prognosis in patients with metabolic disorders is certainly complex, further studies are urgently required to better assess the actual role of these metabolic disorders.

Objectives To test the effect of radiotherapy administered within 6 months after radical prostatectomy on cancer-specific mortality in prostate cancer patients after stratification according to a risk score. Methods Overall, 7616 patients with pT3/4 N0/1 prostate cancer treated with radical prostatectomy between 1995 and 2009 within the Surveillance Epidemiology and End Results Medicare-linked database were included in the study. Competing-risks regression models were carried out to test the effect of early radiotherapy on cancer-specific mortality in the entire cohort, and after stratifying patients according to the risk score based on the number and nature of adverse pathological characteristics (Gleason score 8–10; pT3b/4, lymph node invasion). Results The risk score was associated with increasing 5- and 10-year cancer-specific mortality rates (P

OBJECTIVE: To explore preferences in the management of patients with newly diagnosed high-risk prostate cancer (PCa) among urologists in Europe through a web-based survey. MATERIALS AND METHODS: A web-based survey was conducted between 15 August and 15 September 2013 by members of the Prostate Cancer Working Group of the Young Academic Urologists Working Party of the European Association of Urology (EAU). A specific, 29-item multiple-choice questionnaire covering the whole spectrum of diagnosis, staging and treatment of high-risk PCa was e-mailed to all urologists included in the mailing list of EAU members. Europe was divided into four geographical regions: Central-Eastern Europe (CEE), Northern Europe (NE), Southern Europe (SE) and Western Europe (WE). Descriptive statistics were used. Differences among sample segments were obtained from a z-test compared with the total sample. RESULTS: Of the 12,850 invited EAU members, 585 urologists practising in Europe completed the survey. High-risk PCa was defined as serum PSA >/=20 ng/mL or clinical stage >/= T3 or biopsy Gleason score >/= 8 by 67% of responders, without significant geographical variations. The preferred single-imaging examinations for staging were bone scan (74%, 81% in WE and 70% in SE; P = 0.02 for both), magnetic resonance imaging (53%, 72% in WE and 40% in SE; P = 0.02 and P = 0.01, respectively) and computed tomography (45%, 60% in SE and 23% in WE; P = 0.01 for both). Pre-treatment predictive tools were routinely used by 62% of the urologists, without significant geographical variations. The preferred treatment was radical prostatectomy as the initial step of a multiple-treatment approach (60%, 40% in NE and 70% in CEE; P = 0.02 and P < 0.01, respectively), followed by external beam radiation therapy with androgen deprivation therapy (29%, 45% in NE and 20% in CEE; P = 0.01 and P = 0.02, respectively), and radical prostatectomy as monotherapy (4%, 7% in WE; P = 0.04). When surgery was performed, the open retropubic approach was the most popular (58%, 74% in CEE, 37% in NE; P < 0.01 for both). Pelvic lymph node dissection was performed by 96% of urologists, equally split between a standard and extended template. There was no consensus on the definition of disease recurrence after primary treatment, and much heterogeneity in the administration of adjuvant and salvage treatments. CONCLUSION: With the limitation of a low response rate, the present study is the first survey evaluating preferences in the management of high-risk PCa among urologists in Europe. Although the definition of high-risk PCa was fairly uniform, wide variations in patterns of primary and adjuvant/salvage treatments were observed. These differences might translate into variations in quality of care with a possible impact on ultimate oncological outcome.

Objective To examine and quantify the contemporary association between androgen-deprivation therapy (ADT) and three separate endpoints: coronary artery disease (CAD), acute myocardial infarction (AMI), and sudden cardiac death (SCD), in a large USA contemporary cohort of patients with prostate cancer. Patients and Methods In all, 140 474 patients diagnosed with non-metastatic prostate cancer between 1995 and 2009 within the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database were abstracted. Patients treated with ADT and those not receiving ADT were matched using propensity score methodology. The 10-year CAD, AMI, and SCD rates were estimated. Competing-risks regression analyses tested the association between the type of ADT (GnRH agonists vs bilateral orchidectomy) and CAD, AMI, and SCD, after adjusting for the risk of dying during follow-up. Results Overall, the 10-year rates of CAD, AMI, and SCD were 25.9%, 15.6%, and 15.8%, respectively. After stratification according to ADT status (ADT-naive vs GnRH agonists vs bilateral orchidectomy), the CAD rates were 25.1% vs 26.9% vs 23.2%, the AMI rates were 14.8% vs 16.6% vs 14.8%, and the SCD rates were 14.2% vs 17.7% vs 16.4%, respectively. In competing-risks multivariable regression analyses, the administration of GnRH agonists (all P < 0.001), but not bilateral orchidectomy (all P ≥ 0.7), was associated with higher risk of CAD, AMI, and SCD. Conclusions The administration of GnRH agonists, but not orchidectomy, is still associated with a significantly increased risk of CAD, AMI, and, especially, SCD in patients with non-metastatic prostate cancer. Alternative forms of ADT should be considered in patients at higher risk of CV events.

Objective To describe the survival benefit associated with radical prostatectomy (RP), as compared with initial observation, in patients with locally advanced prostate cancer (PCa). Patients and Methods Overall, 1382 patients with locally advanced PCa treated with RP or initial observation between 1995 and 2009 were identified from the Surveillance, Epidemiology and End Results Medicare insurance programme-linked database. Patients were matched using propensity-score methodology, then 10-year cancer-specific mortality (CSM) rates were estimated and the number needed to treat (NNT) was calculated. Competing-risks regression analyses tested the relationship between treatment type and CSM. Results Overall, the 10-year CSM rates were 11.8 and 19.3% for patients treated with RP and initial observation, respectively (P < 0.001). The corresponding 10-year NNT was 13. The 10-year CSM rates for the same treatment groups were 8.9 vs 13.9%, respectively, for Gleason score ≤7, 16.8 vs 27.8%, respectively, for Gleason score 8–10, 10.1 vs 15.8%, respectively, for clinical stage T3a, and 17.0 vs 29.3%, respectively, for T3b/T4, respectively (all P ≤ 0.04). The corresponding NNTs were 20, 9, 17 and 8, respectively. In multivariable analyses, RP was an independent predictor of more favourable CSM rates in all categories (all P ≤ 0.04). In separate sensitivity analyses, no differences were recorded when patients treated with radiotherapy were compared with those receiving RP (P = 0.4). Conversely, patients undergoing initial observation had a higher risk of CSM compared with those treated with radiotherapy (P = 0.03). Conclusions RP leads to a significant survival advantage compared with observation in patients with locally advanced disease. The highest benefit was observed in patients with T3b/T4 and Gleason score 8–10 disease.