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Background: The role of adjuvant radiotherapy (ART) after radical prostatectomy (RP) on survival of patients with prostate cancer (PCa) is still controversial. Objective: We tested the impact of ART on cancer-specific mortality (CSM) and overall mortality (OM) in PCa patients according to pathologic PCa features. Design, setting, and participants: We evaluated 1049 PCa patients treated with RP and extended pelvic lymph node dissection alone or in combination with adjuvant treatments between 1998 and 2008. All patients had positive surgical margins and/or pT3/pT4 disease with or without positive lymph nodes. Outcome measurements and statistical analysis: Cox regression analyses tested the relationship between pathologic characteristics and CSM rates. Independent predictors of survival were used to develop a novel risk score based on the number of risk factors. Finally, Cox regression models tested the relationship between ART and survival according to the number of risk factors. Results and limitations: On multivariable analyses, only pathologic Gleason score >= 8, pT3b/T4 stage, and presence of positive lymph nodes represented independent predictors of CSM (all p = 0.4). Conversely, in patients with a risk score >= 2, ART was associated with lower CSM and OM rates (all p = 0.006). The observational nature of the cohort represents a limitation of the study. Conclusions: ART significantly improved survival only in patients with at least two of the following pathologic features at RP: Gleason score >= 8, pT3/pT4 disease, and positive lymph nodes. These patients represent the ideal candidates for ART after RP. (c) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Background: Survival after surgical treatment using competing-risk analysis has been previously examined in patients with prostate cancer (PCa). However, the combined effect of age and comorbidities has not been assessed in patients with high-risk PCa who might have heterogeneous rates of competing mortality despite the presence of aggressive disease. Objective: To examine the risk of 10-yr cancer-specific mortality (CSM) and other-cause mortality (OCM) according to clinical and pathologic characteristics of patients treated with radical prostatectomy (RP) for high-risk PCa. Design, setting, and participants: Within a multi-institutional cohort, 3828 men treated with RP for high-risk PCa (defined as the presence of at least one of these risk factors: prostate-specific antigen >20 ng/ml, biopsy Gleason score 8-10, clinical stage >= T3) were identified. Intervention: All patients underwent RP and pelvic lymph node dissection. Outcome measurements and statistical analysis: Competing-risk Poisson regression analyses were performed to simultaneously assess the 10-yr CSM and OCM rates after RP. The same analyses were also conducted after stratification of patients according to age at surgery, comorbidity status assessed by the Charlson Comorbidity Index (CCI), and number of risk factors (one vs two or more). Results and limitations: Overall, 229 patients (5.9%) died from PCa; 549 (14.3%) died from other causes. The 10-yr CSM and OCM rates ranged from 5.1% to 12.8% and from 4.3% to 37.4%, respectively. Age and CCI were the major determinants of OCM; their impact on CSM was minimal. OCM was the leading cause of death in all patient groups except in young men (

Introduction: The aim of our study was to determine the validity of the updated nomogram [Briganti et al.: Eur Urol 2012;61:480-487] as a prediction tool for pelvic lymph node invasion (LNI) in the current era by using a large multicentric population of men who underwent extended pelvic lymph node dissection (ePLND) at the time of radical prostatectomy (RP) at tertiary referral centers. Patients and Methods: Between 2000 and 2011, 896 consecutive patients underwent RP and ePLND at two tertiary referral centers for clinically localized prostate cancer (PCa). Uni- and multivariable logistic regression models predicting the presence of LNI at ePLND were built in. Covariates consisted of preoperative PSA, clinical stage, primary and secondary biopsy Gleason grade with or without percentage of positive cores. Patients' data were entered into a logistic model formula derived from the original publication of Briganti. The nomogram was assessed by comparing its predicted probability of LNI with the actual presence of LNI. The area under the curve was used to quantify its predictive accuracy. Results: Mean preoperative PSA, clinical and pathological stage, primary and secondary biopsy and pathological Gleason grade, such as mean number of total cores, positive cores and percentage of positive cores differed significantly between LNI-positive and LNI-negative patients (all p < 0.001 except for number of total cores, p = 0.019). The mean number of lymph nodes removed was 14.8, and LNI was found in 101 patients (11.8%). In the univariate analysis the percentage of positive cores was the most accurate predictor of LNI (72%), followed by PSA (69%), primary biopsy Gleason grade (64%), clinical stage (60%), and secondary biopsy Gleason grade (59%). The predictions of the nomogram were virtually perfect when the predicted probability was ≤20%. We tested the performance characteristics of various Briganti nomogram-derived cut-offs (1-14%) for discriminating between patients with and without LNI. In our population, 41.6% of patients were classified below the 5% cut-off proposed in the original Briganti et al. report. In the multivariate analysis these variables remained statistically significant predictors for the presence of lymph node metastases. The predictive accuracy of the full model reached 79%. Conclusions: The updated nomogram predicting LNI in patients with PCa undergoing ePLND has been externally validated, demonstrating excellent accuracy and calibration characteristics and a general applicability for predicting the presence of LNI.

Background: Few studies examined the rates of guideline implementation and the survival effect of bladder cuff excision (BCE) at nephroureterectomy (NU). Objective: To assess the rates of guideline implementation regarding NU with BCE relative to NU without BCE in patients with upper tract urothelial carcinoma (UTUC) and to test the effect of BCE on cancer-specific (CSM) and other-cause mortality (OCM). Design, setting, and participants: We relied on Surveillance, Epidemiology, and End Results database (2004–2014) for UTUC of the renal pelvis patients (T1-T3, N0, M0) treated with NU with or without BCE. Outcome measurements and statistical analysis: Cumulative incidence plots relying on competing-risks methodology illustrated 5-yr CSM and OCM rates. Multivariable competing-risks regression (MCRR) models tested the effect of BCE versus no BCE at NU. Results and limitations: Of 4266 assessable patients, 2913 (68.3%) underwent NU with BCE. Between 2004 and 2014, rates of BCE at NU increased from 63.0% to 74.5% (European Association for Palliative Care: 2%; p < 0.001). At 60 mo, CSM rates were 19.7% versus 23.5% (p = 0.005) in NU with BCE versus NU without BCE patients, respectively. In MCRR models, no difference in CSM was recorded according to BCE at NU (hazard ratio [HR]: 0.88, confidence interval [CI]: 0.75–1.03, p = 0.1). Finally, OCM was unaffected by BCE at NU (HR: 0.94, CI: 0.77–1.15, p = 0.5). This study is retrospective. Conclusions: According to guideline recommendation, the rates of NU with BCE increased over time. However, BCE status does not appear to affect CSM or OCM. Thus, our study was unable to examine the rates of urothelial cancer recurrence or metastatic progression according to BCE status. Patient summary: Rates of bladder cuff excision (BCE) at nephroureterectomy (NU) are increasing. This observation confirms improved adherence to guidelines over time. However, BCE status does not appear to affect survival after NU for upper tract urothelial carcinoma.

Context: There is uncertainty regarding the oncologic effectiveness and the survival advantage of local treatment (LT) in men with clinically lymph node-positive (cN+) prostate cancer (PCa). Objective: To systematically review the current literature comparing oncologic outcomes associated with the use of any form of LT for PCa patients with cN+ disease. Evidence acquisition: A computerized bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting comparative oncologic outcomes of LT ± androgen deprivation therapy (ADT) versus ADT alone. LT included both radical prostatectomy (RP) and radiotherapy (RT). Using the methodology recommended by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we identified five nonrandomized comparative retrospective studies published between 1999 and 2018, which were eligible for inclusion in this systematic review. A narrative review and risk-of-bias assessment were performed to determine the impact of LT on recurrence-free survival, cancer-specific survival (CSS), and overall survival (OS). Evidence synthesis: Four studies compared the use of RT ± ADT versus ADT alone, whereas one study compared any form of LT ± ADT versus ADT alone. Different statistical strategies were used in the included studies to account for baseline measured and unmeasured confounders. Overall, the use of RT and, generally speaking, any form of LT was associated with an OS as well as a CSS benefit over ADT alone, without any clear superiority shown either by RP ± ADT or by RT ± ADT. Conclusions: Our systematic review suggests an advantage in terms of both OS and CSS for men with cN+ PCa receiving LT. However, these results should be interpreted with caution due to the low level of evidence of available reports. Patient summary: We reviewed the studies that assessed the role of local treatment in men with prostate cancer and with clinical evidence of lymph node involvement at diagnosis. We found that local treatment was constantly associated with recurrence-free, cancer-specific, and overall survival benefits throughout the included studies. Local treatment for clinically lymph node-positive prostate cancer is constantly associated with recurrence-free, cancer-specific, and overall survival benefits throughout the studies included in this systematic review.

Objective To examine racial disparities in end-of-life (EOL) care among black and white patients dying of prostate cancer (PCa). Methods Relying on the SEER-Medicare database, 3789 patients who died of metastatic PCa between 1999 and 2009 were identified. Information was assessed regarding diagnostic care, therapeutic interventions, hospitalizations, intensive care unit (ICU) admissions, and emergency department visits in the last 12 months, 3 months, and 1 month of life. Logistic regression tested the relationship between race and the receipt of diagnostic care, therapeutic interventions, and high-intensity EOL care. Results Overall, 729 patients (19.24%) were black. In the 12-months preceding death, laboratory tests (odds ratio [OR], 0.51; 95% CI, 0.36-0.72), prostate-specific antigen test (OR, 0.54; 95% CI, 0.43-0.67), cystourethroscopy (OR, 0.71; 95% CI, 0.56-0.90), imaging procedure (OR, 0.58; 95% CI, 0.41-0.81), hormonal therapy (OR, 0.53; 95% CI, 0.44-0.65), chemotherapy (OR, 0.59; 95% CI, 0.48-0.72), radiotherapy (OR, 0.74; 95% CI, 0.61-0.90), and office visit (OR, 0.38; 95% CI, 0.28-0.50) were less frequent in black versus white patients. Conversely, high-intensity EOL care, such as ICU admission (OR, 1.27; 95% CI, 1.04-1.58), inpatient admission (OR, 1.49; 95% CI, 1.09-2.05), and cardiopulmonary resuscitation (OR, 1.72; 95% CI, 1.40-2.11), was more frequent in black versus white patients. Similar trends for EOL care were observed at 3-month and 1-month end points. Conclusions Although diagnostic and therapeutic interventions are less frequent in black patients with end-stage PCa, the rate of high-intensity and aggressive EOL care is higher in these individuals. These disparities may indicate that race plays an important role in the quality of care for men with end-stage PCa.

Background: Robot-assisted radical prostatectomy (RARP) remains controversial, and no improvement in cancer control outcomes has been demonstrated over open radical prostatectomy (ORP). Objective: To examine population-based, comparative effectiveness of RARP versus ORP pertaining surgical margin status and use of additional cancer therapy. Design, setting, and participants: This was a retrospective observational study of 5556 RARP and 7878 ORP cases from 2004 to 2009 from Surveillance Epidemiology and End Results-Medicare linked data. Intervention: RARP versus ORP. Outcome measurements and statistical analysis: Propensity-based analyses were performed to minimize treatment selection biases. Generalized linear regression models were computed for comparison of RP surgical margin status and use of additional cancer therapy (radiation therapy [RT] or androgen deprivation therapy [ADT]) by surgical approach. Results and limitations: In the propensity-adjusted analysis, RARP was associated with fewer positive surgical margins (13.6% vs 18.3%; odds ratio [OR]: 0.70; 95% confidence interval [CI], 0.66-0.75), largely because of fewer RARP positive margins for intermediate-risk (15.0% vs 21.0%; OR: 0.66; 95% CI, 0.59-0.75) and high-risk (15.1% vs 20.6%; OR: 0.70; 95% CI, 0.63-0.77) disease. In addition, RARP was associated with less use of additional cancer therapy within 6 mo (4.5% vs 6.2%; OR: 0.75; 95% CI, 0.69-0.81), 12 mo (OR: 0.73; 95% CI, 0.62-0.86), and 24 mo (OR: 0.67; 95% CI, 0.57-0.78) of surgery. Limitations include the retrospective nature of the study and the absence of prostate-specific antigen levels to determine biochemical recurrence. Conclusions: RARP is associated with improved surgical margin status relative to ORP for intermediate- and high-risk disease and less use of postprostatectomy ADT and RT. This has important implications for quality of life, health care delivery, and costs. Patient summary: Robot-assisted radical prostatectomy (RP) versus open RP is associated with fewer positive margins and better early cancer control because of less use of additional androgen deprivation and radiation therapy within 2 yr of surgery. (C) 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Introduction: Despite a rapid dissemination of robot-assisted radical prostatectomy (RARP) over open radical prostatectomy (ORP), to date no study has compared perioperative outcomes between the two approaches in patients with high-risk prostate cancer (PCa). The aim of our study was to evaluate the safety and feasibility of RARP in this setting. Patients and Methods: Overall, 1,512 patients with high-risk PCa within the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database diagnosed between 2008 and 2009 were abstracted. Patients were treated with RARP or ORP. Postoperative complications, blood transfusions, prolonged length of stay (pLOS), positive surgical margins, and additional cancer therapy rates were compared. Propensity-score matched analyses and logistic regression models fitted with generalized estimating equations for clustering among hospitals were performed. Results: Overall, 706 (46.7%) and 806 (53.3%) patients underwent ORP and RARP, respectively. Following propensity-matched analyses, 706 patients remained. No differences were observed in complications (P=0.6), positive surgical margins (P=0.4), or additional therapy after surgery (P=0.2) between patients treated with RARP and ORP; however, RARP was associated with lower rates of transfusions and shorter hospitalization (all P

Backgrounds Incidence of secondary malignancies and cardiovascular diseases among testicular germ cell tumor (TGCT) survivors is higher compared to the general population. We sought to describe the rates of other-cancer (OCM), non-cancer related (NCRM), and cancer-specific mortality (CSM) among men with TGCT. Methods Using the Surveillance, Epidemiology, and End Results (SEER) database, 31,330 patients with a primary diagnosis of TGCT between 1973 and 2009 were identified. The primary endpoints comprised of 15-year CSM, OCM, and NCRM rates. Survival rates were stratified according to histology (seminoma vs. non-seminoma), median age (

Background and purpose: The aim of this study was to perform a head-to-head comparison of the Roach formula vs. two other newly developed prediction tools for lymph node invasion (LNI) in prostate cancer, namely the Nguyen and the Yu formulas. Material and methods: We included 3115 patients treated with radical prostatectomy and extended pelvic lymph node dissection (ePLND), between 2000 and 2010 at a single center. The predictive accuracy of the three formulas was assessed and compared using the area-under-curve (AUC) and calibration methods. Moreover, decision curve analysis compared the net-benefit of the three formulas in a head-to-head fashion. Results: Overall, 10.8% of patients had LNI. The LNI-predicted risk was >15% in 25.5%, 3.4%, and 10.2% of patients according to the Roach, Nguyen and Yu formula, respectively. The AUC was 80.5%, 80.5% and 79%, respectively (all p > 0.05). However, the Roach formula demonstrated more favorable calibration and generated the highest net-benefit relative to the other examined formulas in decision curve analysis. Conclusions: All formulas demonstrated high and comparable discrimination accuracy in predicting LNI, when externally validated on ePLND treated patients. However, the Roach formula. showed the most favorable characteristics. Therefore, its use should be preferred over the two other tools. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Background: To test the hypothesis that patients with pT2 and positive surgical margins (SM) have a similar biochemical-recurrence (BCR) risk to patients with pT3a, and negative SM. Moreover, we examined the effect of incorporating positive SM as a higher stage on the discrimination accuracy of the current TNM staging system. Materials and methods: We evaluated 1,503 prostate cancer patients treated with radical prostatectomy, between 1998 and 2010. Only individuals with pT2N0 or pT3aN0, without neoadjuvant and/or adjuvant therapy, were included. Cox regression analyses tested the relationship between SM status (negative [R0] vs. positive [R1]) and BCR rate, after stratification according to T stage. Predictive accuracy of the current T stage and of a novel T stage, which consider positive SM as a higher stage, was quantified with Harrell's concordance index. Results: Positive SM rate was 20.3%. The 5-year BCR rates were 96%, 82%, 78%, and 62% for patients with, respectively, pT2R0, pnR1, pT3aR0, and pT3a1 (all P

Background: Data regarding the natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) and adjuvant radiotherapy (aRT) are limited. Objective: To evaluate cancer-specific (CSM) and other-cause mortality (OCM) in prostate cancer patients with BCR after RP and aRT. Design, setting, and participants: We identified 336 patients with BCR treated between 1990 and 2006 at two tertiary care centers. Intervention: All patients underwent RP plus aRT. Outcome measurements and statistical analysis: Cox regression analyses were used to evaluate the association between clinicopathologic variables and CSM. The coefficients of CSM-independent predictors were used to develop a novel nomogram. Patients were stratified into groups according to nomogram-calculated CSM probability and median age. Competing-risks survival analyses were used to estimate CSM and OCM for each group. Results and limitations: Ten-year CSM and OCM were 21.5 and 21.7%, respectively. On multivariable analyses, short time to BCR, pathologic Gleason score >= 8, and positive lymph node count of more than two at RP were significantly associated with increased CSM rate (all p 10-30% versus >30%. On competing-risks analysis, 10-yr CSM rate for these groups was 6%, 15%, and 42%, respectively, for patients aged 68 yr. Likewise, 10-yr OCM rate was 24%, 9%, and 10%, respectively, for patients aged 68 yr. The study is limited by its retrospective design. Conclusions: Short time to BCR, pathologic Gleason score >= 8, and more than two positive lymph nodes were independent predictors of CSM in patients with BCR after RP and aRT. Men with these features may benefit from additional secondary therapies, ideally, in a clinical trial setting. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Purpose: To examine the overall and stage-specific age-adjusted incidence, 5-year survival and mortality rates of bladder cancer (BCa) in the United States, between 1973 and 2009. Materials and methods: A total of 148,315 BCa patients were identified in the Surveillance, Epidemiology and End Results database, between years 1973 and 2009. Incidence, mortality, and 5-year cancer-specific survival rates were calculated. Temporal trends were quantified using the estimated annual percentage change (EAPC) and linear regression models. All analyses were stratified according to disease stage, and further examined according to sex, race, and age groups. Results: Incidence rate of BCa increased from 21.0 to 25.5/100,000 person-years between 1973 and 2009. Stage-specific analyses revealed an increase incidence for localized stage: 15.4-20.2 (EAPC: +0.5%, p < 0.001) and distant stage: 0.5-0.8 (EAPC: +0.7%, p = 0.001). Stage-specific 5-year survival rates increased for all stages, except for distant disease. No significant changes in mortality were recorded among localized (EAPC: -0.2%, p = 0.1) and regional stage (EAPC: -0.1%, p = 0.5). An increase in mortality rates was observed among distant stage (EAPC: +1.0%, p = 0.005). Significant variations in incidence and mortality were recorded when estimates were stratified according to sex, race, and age groups. Discussion: Albeit statistically significant, virtually all changes in incidence and mortality were minor, and hardly of any clinical importance. Little or no change in BCa cancer control outcomes has been achieved during the study period. (C) 2013 Elsevier Ltd. All rights reserved.

The therapeutic effect of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) due to prostate cancer (PCa) is still under debate. We aimed at assessing the impact of more extensive PLND on cancer-specific mortality (CSM) in patients treated with surgery for locally advanced PCa.We examined data of 1586 pT3-T4 PCa patients treated with RP and extended PLND between 1987 and 2012 at a tertiary referral care center. Univariable and multivariable Cox regression analyses tested the relationship between the number of nodes removed and CSM rate, after adjusting for potential confounders. Survival estimates were based on the multivariable models.The average number of nodes removed was 19 (median: 17; interquartile range: 11-23). Mean and median follow-up were 80 and 72 months, respectively. At multivariable analyses, Gleason score 8-10 (hazard ratio (HR): 2.5) and a higher number of positive nodes (HR: 1.06) were independently associated with higher CSM rate (all P0.05). Conversely, higher number of removed LNs (HR: 0.94) and adjuvant radiotherapy (HR: 0.54) were independent predictors of lower CSM rates (all P⩽0.03).In pT3-T4 PCa patients, removal of a higher number of LNs during RP was associated with higher cancer-specific survival rates. This supports the role of more extensive PLNDs in this patient group. Further prospective studies are needed to validate our findings.

Introduction Extended pelvic lymph node dissection (ePLND) might be associated with damages to the pelvic plexus, potentially affecting erectile function (EF) recovery after radical prostatectomy (RP). However, the impact of the extent of pelvic lymph node dissection (PLND) on EF has never been addressed. Aim The aim of this study is to evaluate the impact of ePLND on potency recovery in patients who underwent bilateral nerve‐sparing RP (BNSRP). Methods The study included 396 patients with prostate cancer treated with BNSRP by two high‐volume surgeons. Patients were retrospectively divided into two groups based on PLND status: no PLND (N = 161; 40.9%) and ePLND (N = 235; 59.1%) at the time of BNSRP. All patients had preoperative functional and oncological data. Univariable and multivariable Cox regression models tested the association between ePLND and EF recovery after surgery, after accounting for confounders. Main Outcome Measure The International Index of Erectile Function (IIEF) was used to evaluate EF after BNSRP. Postoperative EF recovery was defined as an IIEF‐EF domain score ≥22. Results At a mean follow up of 33.2 months after surgery (median 30), 183 patients (46.2%) recovered EF. Overall, postoperative EF recovery rate at 2 years was 48.4%. No significant differences were recorded when patients were stratified according to the extent of PLND (EF recovery rates at 2‐year: 46.6% vs. 49.7% for patients who did not undergo PLND vs. those treated with ePLND; P = 0.33). These results were confirmed at multivariable analyses, where only age at surgery and preoperative IIEF‐EF (all P ≤ 0.03), but not ePLND ( P = 0.8), represented independent predictors of EF recovery. Conclusions The extent of PLND is not associated with potency after BNSRP. Conversely, other factors such as age at surgery and preoperative EF represent the major predictors of postoperative potency recovery. Therefore, when indicated, ePLND can be safely performed without compromising EF outcomes. Gandaglia G, Suardi N, Gallina A, Abdollah F, Capitanio U, Salonia A, Colombo R, Bianchi M, Chun FK, Hansen J, Rigatti P, Montorsi F, and Briganti A. Extended pelvic lymph node dissection does not affect erectile function recovery in patients treated with bilateral nerve‐sparing radical prostatectomy. J Sex Med 2012;9:2187–2194.

Background: The current role of radical prostatectomy (RP) in patients with high-risk disease remains controversial. Objective: To identify which high-risk prostate cancer (PCa) patients might have favorable pathologic outcomes when surgically treated. Design, setting, and participants: We evaluated 1366 patients with high-risk PCa (ie, at least one of the following risk factors: prostate-specific antigen [PSA] > 20 ng/ml, cT3, biopsy Gleason 8-10) treated with RP and pelvic lymph node dissection (PLND) at eight European centers between 1987 and 2009. A favorable pathologic outcome was defined as specimen-confined (SC) disease-namely, pT2-pT3a, node negative PCa with negative surgical margins. Intervention: All patients underwent radical retropubic prostatectomy and PLND. Measurements: Univariable and multivariable logistic regression models tested the association between predictors and SC disease. A logistic regression coefficient-based nomogram was developed and internally validated using 200 bootstrap resamples. The Kaplan-Meier method was used to depict biochemical recurrence (BCR) and cancer-specific survival (CSS) rates. Results and limitations: Overall, 505 of 1366 patients (37%) had SC disease at RP. All preoperative variables (ie, age and PSA at surgery, clinical stage, and biopsy Gleason sum) were independent predictors of SC PCa at RP (all p

Purpose: The association between baseline functional status and urinary continence recovery after radical prostatectomy remains controversial. We tested the hypothesis that baseline erectile and urinary function predicts urinary continence recovery after bilateral nerve sparing radical prostatectomy. Materials and Methods: The study included 752 patients with prostate cancer treated with bilateral nerve sparing radical prostatectomy between 2003 and 2009. All patients had preoperative functional and oncological data available, including age at surgery, body mass index, prostate specific antigen, and erectile and urinary function. Preoperatively erectile and urinary function was assessed by the erectile function domain of the International Index of Erectile Function and the International Prostatic Symptoms Score. Urinary continence was defined as wearing no pads. Univariate and multivariate Cox regression models were used to test the association between predictors and urinary continence recovery after surgery. Results: At a mean postoperative followup of 30.7 months (median 29, range 1 to 80) 611 patients (81.3%) had recovered urinary continence. Overall the urinary continence recovery rate at 1 and 3 years was 73.9% and 82.2%, respectively. On univariate Cox regression analysis patient age and the preoperative score on the erectile function domain of the International Index of Erectile Function were significantly associated with urinary continence recovery (each p

Background: To examine the use of open partial nephrectomy (OPN) and laparoscopic partial nephrectomy (LPN), as well as intraoperative and postoperative morbidity. Materials and methods: A retrospective cohort analysis of the Nationwide Inpatient Sample for years 1998-2007. Patients with non-metastatic kidney cancer who underwent OPN or LPN were identified. Propensity-based matching was performed to adjust for potential baseline differences between the two groups. The rates of intraoperative and postoperative complications, blood transfusions, length of stay, and in-hospital mortality were assessed for both procedures. Results: Overall, 7990 (93.9%) and 523 (6.1%) patients underwent OPN and LPN, respectively. Use of LPN increased 19-fold over the study period (P < 0.001). For OPN and LPN respectively, the following rates were recorded: blood transfusions, 9.3 vs. 3.8% (P < 0.001); intraoperative complications, 2.9 vs. 1.5% (P = 0.06); postoperative complications, 15.4 vs. 11.3% (P = 0.01); length of stay >= 5 days, 46.7 vs. 20.8% (P < 0.001); in-hospital mortality, 0.4 vs. 0.4% (P = 0.98). In multivariable logistic regression analyses, LPN patients were less likely to have a blood transfusion (odds ratio [OR]: 0.40, P < 0.001), to experience any postoperative complication (OR: 0.74, P = 0.03), and to be hospitalized for more than 5 days (OR: 0.32, P < 0.001). Post-propensity score matched analyses revealed virtually the same results. Conclusions: After adjustment for potential selection biases, LPN is associated with fewer adverse outcomes than OPN. However, the current results should be interpreted with caution, given the lack of tumor characteristics. Furthermore, statistical adjustment is not a substitute for a needed randomized trial. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

Background: The management of patients with clinical recurrence of prostate cancer after radical prostatectomy (RP) remains challenging. Objective: To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography (PET/CT) scan may have an impact on the prognosis of patients with biochemical recurrence (BCR) and nodal recurrence after RP. Design, setting, and participants: Prospective analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan. Intervention: Patients underwent salvage lymph node dissection (LND). Measurements: Biochemical response (BR) to treatment was defined as prostate-specific antigen (PSA) < 0.2 ng/ml at 40 d after salvage LND. Kaplan-Meier and Cox regression analyses addressed time to and predictors of clinical recurrence (CR) after salvage LND, respectively. Results and limitations: Overall, 56.9% of patients achieved BR. Mean and median follow-up after LND were 39.4 and 39.8 mo, respectively. The 5-yr BCR-free survival rate was 19%. Preoperative PSA < 4 ng/ml (hazard ratio [HR]: 0.12; p = 0.005), time to BCR < 24 mo (HR: 7.52; p = 0.005), and negative lymph nodes at previous RP (HR: 0.19; p = 0.04) represented independent predictors of BR. Overall, 5-yr CR-free and cancer-specific survival were 34% and 75%, respectively. At multivariable analyses, only PSA >4 ng/ml (HR: 2.13; p = 0.03) and the presence of retroperitoneal uptake at PET/CT scan (HR = 2.92; p = 0.004) represented independent preoperative predictors of CR. Similarly, the presence of pathologic nodes in the retroperitoneum (HR: 2.78; p = 0.02), higher number of positive lymph nodes (HR: 1.04; p = 0.006), and complete BR to salvage LND (HR: 0.31; p = 0.002) represented postoperative independent predictors of CR. Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses. Conclusions: Salvage LND is feasible in patients with BCR after RP and nodal pathologic uptake at [11C]choline PET/CT scan. Biochemical response after surgery can be achieved in a consistent proportion of patients. Although most patients invariably progressed to BCR after surgery at longer follow-up, 35% of patients showed the absence of CR at 5 yr. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. "Background: The management of patients with clinical recurrence of prostate cancer after radical prostatectomy (RP) remains challenging. Objective: To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography (PET/CT) scan may have an impact on the prognosis of patients with biochemical recurrence (BCR) and nodal recurrence after RP. Design, setting, and participants: Prospective analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan. Intervention: Patients underwent salvage lymph node dissection (LND). Measurements: Biochemical response (BR) to treatment was defined as prostate-specific antigen (PSA) < 0.2 ng/ml at 40 d after salvage LND. Kaplan-Meier and Cox regression analyses addressed time to and predictors of clinical recurrence (CR) after salvage LND, respectively. Results and limitations: Overall, 56.9% of patients achieved BR. Mean and median follow-up after LND were 39.4 and 39.8 mo, respectively. The 5-yr BCR-free survival rate was 19%. Preoperative PSA < 4 ng/ml (hazard ratio [HR]: 0.12; p = 0.005), time to BCR < 24 mo (HR: 7.52; p = 0.005), and negative lymph nodes at previous RP (HR: 0.19; p = 0.04) represented independent predictors of BR. Overall, 5-yr CR-free and cancer-specific survival were 34% and 75%, respectively. At multivariable analyses, only PSA >4 ng/ml (HR: 2.13; p = 0.03) and the presence of retroperitoneal uptake at PET/CT scan (HR = 2.92; p = 0.004) represented independent preoperative predictors of CR. Similarly, the presence of pathologic nodes in the retroperitoneum (HR: 2.78; p = 0.02), higher number of positive lymph nodes (HR: 1.04; p = 0.006), and complete BR to salvage LND (HR: 0.31; p = 0.002) represented postoperative independent predictors of CR. Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses. Conclusions: Salvage LND is feasible in patients with BCR after RP and nodal pathologic uptake at [11C]choline PET/CT scan. Biochemical response after surgery can be achieved in a consistent proportion of patients. Although most patients invariably progressed to BCR after surgery at longer follow-up, 35% of patients showed the absence of CR at 5 yr. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved."

"Purpose: National Comprehensive Cancer Network practice guidelines indicate that pelvic lymph node dissection can be omitted at radical cystectomy in elderly patients. We examined the pelvic lymph node dissection rate in patients 80 years old or older and the impact of pelvic lymph node dissection on cancer specific and overall mortality in these patients. Materials and Methods: We examined the records of 11,183 patients treated with radical cystectomy in 17 Surveillance, Epidemiology and End Results registries. We performed univariate and multivariate Cox regression analysis to test the effect of pelvic lymph node dissection on cancer specific and overall mortality. Results: Overall pelvic lymph node dissection was omitted in 25% of patients, including 24.2% younger than 80 years and 30.8% 80 years old or older (p < 0.001). The 5-year rate of freedom from cancer specific mortality for pelvic lymph node dissection vs no pelvic lymph node dissection was 62.5% vs 59.9% in patients younger than 80 years, and 50.0% vs 46.1% in those 80 years old or older (p = 0.01 and 0.005, respectively). The 5-year rate of freedom from overall mortality for the same categories was 48.8% vs 43.9% and 28.3% vs 24.7% (p < 0.001 and 0.01, respectively). On multivariate analysis omitting pelvic lymph node dissection was associated with a 1.3-fold higher cancer specific rate at ages less than 80 and 80 years or greater (each p < 0.001). Omitting pelvic lymph node dissection was also associated with a 1.3-fold higher overall mortality rate, including 1.3 at ages less than 80 years and 1.2-fold at ages 80 years or greater (each p

The objective was to test the hypothesis that in patients with prostate cancer undergoing radical prostatectomy (RP), diabetic patients are at a higher risk of harboring a high-grade tumor than nondiabetic patients. We examined 2060 consecutive men who underwent RP between 2001 and 2009. Of them, 7.1% had type 2 diabetes mellitus (DM). A high-grade tumor was defined as having a Gleason score >= 8. Univariable and multivariable logistic regression analyses were used to test the relationship between type 2 DM and high-grade tumor. Mean patient age was 64 years (range: 45-85). Mean total PSA level was 9 ng ml(-1) (range: 1-89.5). A significantly higher percentage of diabetic patients had high-grade tumor on biopsy (16.3 vs 7.6%; P=0.001) and on RP specimen (21.1 vs 11.7%; P-0.001) in comparison with non-diabetic patients. In multivariable analyses, DM was an independent predictor of high-grade tumor on biopsy (odds ratio 2.31, P=0.001) and on final pathological specimen (odds ratio 2.22, P=0.002). In patients undergoing RP, those with type 2 DM had a higher risk of harboring a poorly differentiated tumor on final pathological examination. Prostate Cancer and Prostatic Diseases (2011) 14, 74-78; doi: 10.1038/pcan.2010.41; published online 19 October 2010 "The objective was to test the hypothesis that in patients with prostate cancer undergoing radical prostatectomy (RP), diabetic patients are at a higher risk of harboring a high-grade tumor than nondiabetic patients. We examined 2060 consecutive men who underwent RP between 2001 and 2009. Of them, 7.1% had type 2 diabetes mellitus (DM). A high-grade tumor was defined as having a Gleason score >= 8. Univariable and multivariable logistic regression analyses were used to test the relationship between type 2 DM and high-grade tumor. Mean patient age was 64 years (range: 45-85). Mean total PSA level was 9 ng ml(-1) (range: 1-89.5). A significantly higher percentage of diabetic patients had high-grade tumor on biopsy (16.3 vs 7.6%; P=0.001) and on RP specimen (21.1 vs 11.7%; P-0.001) in comparison with non-diabetic patients. In multivariable analyses, DM was an independent predictor of high-grade tumor on biopsy (odds ratio 2.31, P=0.001) and on final pathological specimen (odds ratio 2.22, P=0.002). In patients undergoing RP, those with type 2 DM had a higher risk of harboring a poorly differentiated tumor on final pathological examination. Prostate Cancer and Prostatic Diseases (2011) 14, 74-78; doi: 10.1038\/pcan.2010.41; published online 19 October 2010"

Purpose of review Holmium laser enucleation of the prostate (HoLEP) has been proposed as an alternative to transurethral resection of the prostate and to open prostatectomy for patients with lower urinary tract symptoms because of large benign prostatic enlargement. The aim of this review is to critically analyze currently available evidence-based reports regarding HoLEP, with particular interest in long-term follow-up results. Recent findings The use of holmium laser for the treatment of benign prostatic hyperplasia was first reported in 1996. HoLEP seems to represent a valid alternative to both transurethral resection of the prostate and open prostatectomy, with valid long-term functional results, a low rate of short-term and long-term complications, and very low rates of reintervention. Summary HoLEP represents a valid alternative to both transurethral resection of the prostate and open prostatectomy for treatment of patients suffering from lower urinary tract symptoms due to benign prostatic enlargement. The recently published long-term follow-up data demonstrate the durability of functional results. HoLEP can be offered as the size-independent gold standard treatment of patients with lower urinary tract symptoms because of benign prostatic enlargement. Purpose of review Holmium laser enucleation of the prostate (HoLEP) has been proposed as an alternative to transurethral resection of the prostate and to open prostatectomy for patients with lower urinary tract symptoms because of large benign prostatic enlargement. The aim of this review is to critically analyze currently available evidence-based reports regarding HoLEP, with particular interest in long-term follow-up results. Recent findings The use of holmium laser for the treatment of benign prostatic hyperplasia was first reported in 1996. HoLEP seems to represent a valid alternative to both transurethral resection of the prostate and open prostatectomy, with valid long-term functional results, a low rate of short-term and long-term complications, and very low rates of reintervention. Summary HoLEP represents a valid alternative to both transurethral resection of the prostate and open prostatectomy for treatment of patients suffering from lower urinary tract symptoms due to benign prostatic enlargement. The recently published long-term follow-up data demonstrate the durability of functional results. HoLEP can be offered as the size-independent gold standard treatment of patients with lower urinary tract symptoms because of benign prostatic enlargement.

Context: Erectile dysfunction (ED) is the complication associated with radical prostatectomy (RP) for clinically localized prostate cancer that has the most negative impact. Currently, several therapeutic options are available to improve sexual health after surgical treatment. Objective: To critically analyze the factors affecting erectile function after RP and to evaluate the evidence suggesting the role of pharmacologic prophylaxis and treatment of ED after surgery. Evidence acquisition: This article is based on the proceeding of the Risk Evaluation and Mitigation Strategy (REMS) meeting held in Madrid, Spain, in 2007. Evidence synthesis: Several basic science reports have highlighted a potential role of phosphodiesterase type 5 inhibitors (PDE5-Is) in the prevention of endothelial damage related to ischemia-reperfusion and/or denervation following surgery. However, patient selection and preservation of both nerves and vascular supply integrity are the major determinants of postoperative erectile function. Pharmacologic treatment of postoperative ED, using either oral or local approaches, is effective and safe. Moreover, recent studies have shown that pharmacologic prophylaxis early after RP can significantly improve the rate of erectile function recovery after surgery. Use of on-demand treatments for treatment of ED in post-RP patients has been shown to be highly effective. in this context, pharmacologic prophylaxis may potentially have a significant expanding role in future strategies aimed at preserving postoperative erectile function. Conclusions: Administration of pro-erectile drugs is the key factor of erectile function recovery after RP. Use of on-demand PDES-Is in post-RP patients has been shown to be effective and safe, with better results seen in select young patients treated with a bilateral nerve-sparing approach. Pharmacologic prophylaxis may have a role in the future. Large, multicentric, placebo-controlled trials are urgently needed in order to identify the best regimen for treating postsurgery ED. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. Context: Erectile dysfunction (ED) is the complication associated with radical prostatectomy (RP) for clinically localized prostate cancer that has the most negative impact. Currently, several therapeutic options are available to improve sexual health after surgical treatment. Objective: To critically analyze the factors affecting erectile function after RP and to evaluate the evidence suggesting the role of pharmacologic prophylaxis and treatment of ED after surgery. Evidence acquisition: This article is based on the proceeding of the Risk Evaluation and Mitigation Strategy (REMS) meeting held in Madrid, Spain, in 2007. Evidence synthesis: Several basic science reports have highlighted a potential role of phosphodiesterase type 5 inhibitors (PDE5-Is) in the prevention of endothelial damage related to ischemia-reperfusion and/or denervation following surgery. However, patient selection and preservation of both nerves and vascular supply integrity are the major determinants of postoperative erectile function. Pharmacologic treatment of postoperative ED, using either oral or local approaches, is effective and safe. Moreover, recent studies have shown that pharmacologic prophylaxis early after RP can significantly improve the rate of erectile function recovery after surgery. Use of on-demand treatments for treatment of ED in post-RP patients has been shown to be highly effective. in this context, pharmacologic prophylaxis may potentially have a significant expanding role in future strategies aimed at preserving postoperative erectile function. Conclusions: Administration of pro-erectile drugs is the key factor of erectile function recovery after RP. Use of on-demand PDES-Is in post-RP patients has been shown to be effective and safe, with better results seen in select young patients treated with a bilateral nerve-sparing approach. Pharmacologic prophylaxis may have a role in the future. Large, multicentric, placebo-controlled trials are urgently needed in order to identify the best regimen for treating postsurgery ED. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Cancer control outcomes following robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) remain inadequately addressed over intermediate-term (≥5-year) follow-up. We examined biochemical recurrence-free survival (BCRFS), clinical recurrence-free survival (CRFS), and cancer-specific survival (CSS) in a multi-institutional cohort of men undergoing RARP for localized PCa. A total of 5670 PCa patients undergoing RARP ± pelvic lymph node dissection as primary treatment modality at three tertiary care centers between 2001 and 2010 were analyzed. BCRFS, CRFS, and CSS were estimated using the Kaplan–Meier method. Cox proportional hazards model tested their association with available preoperative and postoperative parameters. 43.6 and 15.1 % of patients had D’Amico intermediate- and high-risk disease, respectively. Over a mean (median) follow-up of 56 (50.4) months, 797 men had a BCR, 78 men had CR, and 32 men died of PCa. Actuarial BCRFS, CRFS, and CSS, respectively, were 83.3, 98.6, and 99.5 % at 5-year; 76.5, 97.5, and 98.7 % at 8-year; and 73.3, 96.7, and 98.4 % at 10-year follow-ups. Only 1.7 % of patients received any adjuvant treatment. Preoperative prostate-specific antigen (PSA) and biopsy Gleason score (GS) were independent clinical predictors of BCRFS, CRFS, and CSS, while postoperatively positive surgical margin, pathological GS, pathological stage, and lymph node invasion were significantly associated with BCR and CR (all p

Purpose To compare long-term cancer outcomes after radical cystectomy (RC) alone or RC with pelvic lymph node dissection (PLND) according to different age and comorbidities categories. Methods Using the SEER-Medicare dataset, 3314 patients diagnosed with urothelial carcinoma of the urinary bladder and treated with RC alone or RC with PLND were identified. After propensity score matching to reduce potential selection bias, all cause mortality (ACM)-free and cancer specific mortality (CSM)-free survival rates were estimated. Multivariable regression models (MVA) addressed the effect of PLND on ACM and CSM. Subgroups analyses according to age and comorbidities were performed. Results After matching, 688 and 688 patients treated with RC alone or RC with PLND remained. The 5-year ACM-free survival rate was 36 after RC alone and 45% after RC with PLND (p < 0001). In MVA, PLND exerted a protective effect on ACM (HR 0.77, p < 0.001). The 5-year CSM-free survival rate was 54 after RC alone and 65% after RC with PLND (p < 0.001). In MVA, PLND exerted a protective effect on CSM (HR 0.71, p < 0.001). Similar results were observed in younger (age ≤75) and healthier (CCI = 0) patients, where PLND exerted a protective effect on ACM (HR 0.64, p = 0.001) and CSM (HR 0.65, p = 0.01). Conversely, in older (age >75) and sicker (CCI ≤1) patients, PLND was not associated with ACM (HR 0.98, p = 0.8) or CSM (HR 1.01, p = 0.9). Conclusions RC with PLND is associated with improved all cause and cancer specific survival in younger and healthier RC candidates but not in older and sicker patients.

Background: The role of extended pelvic lymph node dissection (ePLND) in treating prostate cancer (PCa) patients with lymph node invasion (LNI) remains controversial. Objective: The relationship between the number of removed lymph nodes (RLNs) and cancer-specific mortality (CSM) was tested in patients with LNI. Design, setting, and participants: We examined data of 315 pN1 PCa patients treated with radical prostatectomy (RP) and anatomically ePLND between 2000 and 2012 at one tertiary care centre. All patients received adjuvant hormonal therapy with or without adjuvant radiotherapy (aRT). Outcome measurements and statistical analysis: Univariable and multivariable Cox regression analyses tested the relationship between RLN number and CSM rate, after adjusting to all available covariates. Survival estimates were based on the multivariable model; patients were stratified according to RLN number using points of maximum separation. Results and limitations: The average number of RLNs was 20.8 (median: 19; interquartile range: 14–25). Mean and median follow-up were 63.1 and 54 mo, respectively. At 10-yr, the CSM-free survival rate was 74.7%, 85.9%, 92.4%, 96.0%, and 97.9% for patients with 8, 17, 26, 36, and 45 RLNs, respectively. By multivariable analyses, the number of RLNs independently predicted lower CSM rate (hazard ratio [HR]: 0.93; p = 0.02). Other predictors of CSM were Gleason score 8–10 (HR: 3.3), number of positive nodes (HR: 1.2), and aRT treatment (HR: 0.26; all p 0.006). The study is limited by its retrospective nature. Conclusions: In PCa patients with LNI, the removal of a higher number of LNs during RP was associated with improvement in cancer-specific survival rate. This implies that ePLND should be considered in all patients with a significant preoperative risk of harbouring LNI. Patient summary: We found that removing more lymph nodes during prostate cancer surgery can significantly improve cancer-specific survival in patients with lymph node invasion.

Pelvic lymph node dissection (PLND) represents one of the most intriguing topics in the management of prostate cancer (PCa). For years, the decision to perform PLND and to what extent has been left to the clinical judgment of each treating physician. As indeed often happens inmedicine, the lack of a clear benefit of any treatment (either pharmacologic or surgical) opens the doors to a wide variety of experience-based approaches. Some urologists did not consider PLND useful at all, since radical prostatectomy (RP) was reserved only for patients with favourable PCa and, thus, at low risk of nodal metastases. Patients with high-risk disease were not even treated with surgery due to the presumed high probability of being affected by systemic disease. All the recent series reporting excellent outcomes after RP inmenwith high-risk disease have clearly demonstrated the inadequacy of such approach [1]. For those few patients receiving surgery for more aggressive disease, PLND was often not extended beyond the obturator fossa. Again, this was due to the wrong assumption that lymph nodes located in this area represented the only primary lymphatic drainage of the prostate. In these cases, PLND was given only a (small) staging significance. Conversely, other urologists did consider it useful to extend PLND to several pelvic lymphatic landing sites. This was done whenever RP was indicated and performed. These clinicians well knew the complex lymphatic drainage of the prostate. However, the main question was whether this extensive approach could improve disease control. In the view of these urologists, removal of micrometastatic disease could only be beneficial for patients, even in the absence of solid, prospective data. The scepticismof opponentswasmet most frequently with the question, ‘‘If this is true for the vast majority of cancers, why should it be different for prostate?’’ Finally, other urologists did perform extended PLND (ePLND) in highly selected patients treated with RP. This was done to spare morbidity of ePLND to a certain proportion of patients with less aggressive disease. Why expose patients to higher rates of complications in the absence of a real proof of benefit of ePLND on cancer control? Morbidity has always been the Trojan horse for those reluctant to deliver ePLND. However, the equation more extensive PLND equals higher rates of complications has not always been confirmed [2,3]. Moreover, no serious concerns about complications were raised (at least not very often) when addressing the role of ePLND in bladder cancer, given the fact that a meticulous PLND can save lives in that setting. The risk in that case, urologists said, is justified. This heterogeneity in personal views created heterogeneous patient series that precluded any objective wellperformed evaluation of the role of ePLND on PCa control. Inadequate templates of PLND given on the basis of different indications by different surgeons were often merged in the same retrospective series. Not surprisingly, no association between PLND and PCa outcomes was found [4]. Similarly, none of the series in whichmeticulous PLNDwas invariably performed in all patients was able to assess the impact of ePLND for one main reason: the lack of a corresponding comparable group not receiving PLND. So, how do we solve this problem? The answer to this question is coming from recent high-quality reports, such as the studyby Joniau et al. [5]. Theseworkshave contributed to meeting two needs in this field: (1) standardisation of the anatomic extent of PLND and (2) indication for ePLND itself. E U RO P E AN URO LOGY 6 3 ( 2 0 1 3 ) 4 5 9 – 4 6 1

A recent study observed a survival benefit in men diagnosed with metastatic prostate cancer (mPCa) and managed with local treatment of the primary tumor (LT; either radical prostatectomy plus pelvic lymph node dissection or radiation therapy). We tested the hypothesis that only specific mPCa patients would benefit from LT and that the potential benefit would vary based on primary tumor characteristics. A total of 8197 mPCa patients at diagnosis (M1a, M1b, and M1c) were identified using the Surveillance Epidemiology and End Results database (2004-2011) and were divided according to treatment type: LT versus nonlocal treatment of the primary tumor (NLT; either androgen deprivation therapy or observation). Multivariable Cox regression analysis was used to predict cancer-specific mortality (CSM) in patients that received NLT. To assess whether the benefit of LT was different by baseline risk, we tested an interaction with CSM risk and LT. At multivariable analysis, all predictors were significantly associated with CSM, and the interaction test was statistically significant (p < 0.0001). Local treatment of the primary tumor, compared with NLT, conferred a higher CSM-free survival rate in patients with a predicted CSM risk 40%. These results should serve as a foundation for future prospective trials. Patient summary Among metastatic prostate cancer patients, the potential benefit of local treatment to the primary tumor depends greatly on tumor characteristics, and patient selection is essential to avoid either over- or undertreatment.

Objective To evaluate the effect of advancing age on cancer-specific mortality (CSM) after radical prostatectomy (RP). Materials and methods Overall, 205,551 patients with PCa diagnosed between 1988 and 2009 within the Surveillance Epidemiology and End Results (SEER) database were included in the study. Patients were stratified according to age at diagnosis: ≤&50, 51-60, 61-70, and ≥71 years. The 15-year cumulative incidence CSM rates were computed. Competing-risks regression models were performed to test the effect of age on CSM in the entire cohort, and for each grade (Gleason score 2-4, 5-7, and 8-10) and stage (pT2, pT3a, and pT3b) sub-cohorts. Results Advancing age was associated with higher 15-year CSM rates (2.3 vs. 3.4 vs. 4.6 vs. 6.3% for patients aged ≤;50 vs. 51-60 vs. 61-70 vs. ≥71 years, respectively; P < 0.001). In multivariable analyses, age at diagnosis was a significant predictor of CSM. This relationship was also observed in sub-analyses focusing on patients with Gleason score 5-7, and/or pT2 disease (all P ≤& 0.05). Conversely, age failed to reach the independent predictor status in men with Gleason score 2-4, 8-10, pT3a, and/or pT3b disease. Conclusions Advancing age increases the risk of CSM. However, when considering patients affected by more aggressive disease, age was not significantly associated with higher risk of dying from PCa. In high-risk patients, tumor characteristics rather than age should be considered when making treatment decisions.

Background:Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status.Methods:We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes.Results:In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1-6 nodes in cT1 and 6-8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively.Conclusions:Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis. © 2014 Cancer Research UK.

Background Androgen deprivation therapy (ADT) might increase the risk of acute kidney injury (AKI) in patients with prostate cancer (PCa).Design, setting, and participants Overall, 69 292 patients diagnosed with nonmetastatic PCa between 1995 and 2009 were abstracted from the Surveillance Epidemiology and End Results-Medicare database. Outcomes measurements and statistical analyses Patient in both treatment arms (ADT vs no ADT) were matched using propensity-score methodology. Ten-year AKI rates were estimated. Competing-risks regression analyses tested the association between ADT and AKI, after adjusting for the risk of death during follow-up.Patient summary The administration of gonadotropin-releasing hormone agonists, but not bilateral orchiectomy, increases the risk of acute kidney injury (AKI) in patients with prostate cancer (PCa). These observations should help provide physicians with better patient selection to reduce the risk of AKI in PCa patients.Results and limitations Overall, the 10-yr AKI rates were 24.9% versus 30.7% for ADT-naive patients versus those treated with ADT, respectively (p < 0.001). When patients were stratified according to the type of ADT, the 10-yr AKI rates were 31.1% versus 26.0% for men treated with gonadotropin-releasing hormone (GnRH) agonists and bilateral orchiectomy, respectively (p < 0.001). In multivariable analyses, the administration of GnRH agonists (hazard ratio [HR]: 1.24; 95% confidence interval [CI], 1.18-1.31; p < 0.001), but not bilateral orchiectomy (HR: 1.11; 95% CI, 0.96-1.29; p = 0.1), was associated with the risk of experiencing AKI. Our study is limited by its retrospective design.Conclusions ADT is associated with an increased risk of AKI in patients with nonmetastatic PCa. In particular, the administration of GnRH agonists, but not surgical castration, may substantially increase the risk of experiencing AKI. These observations should help provide physicians with better patient selection to reduce the risk of AKI.

Several studies have shown that 11C-choline PET/CT may be useful for restaging prostate cancer (PCa) patients with biochemical failure after radical prostatectomy. However, validation of 11C-choline PET/CT findings scarcely relied on histologic findings, and prognostic implications of 11C-choline PET/CT are currently unknown. The aim of this study was to assess whether 11C-choline PET/CT predicts survival in PCa patients. Methods: This retrospective study included 195 PCa patients treated with radical prostatectomy who underwent 11C-choline PET/CT from December 1, 2004, to July 31, 2007, due to biochemical failure (prostate-specific antigen > 0.2 mg/mL) during androgen-deprivation therapy. PCa-specific survival was computed as the interval from radical prostatectomy to PCa-specific death. Results: The median interval after radical prostatectomy was 8.9 y (95% confidence interval [CI], 1.7-18.9 y). The median follow-up after 11C-choline PET/CT was 4.5 y (95% CI, 0.4-8.5 y). 11C-choline PET/CT results were positive in 57% of patients. The median PCa-specific survival was 16.4 y (95% CI, 14.0-18.8 y) in patients with negative 11C-choline PET/CT results and 11.2 y (95% CI, 9.8-12.6 y) in patients with positive 11C-choline PET/CT results (log-rank: x2 = 19.3, P < 0001). At multivariate analysis, statistical significance was obtained for 11C-choline PET/CT (hazard ratio, 2.53; 95% CI, 1.41-4.53; P = 0.002), prostate-specific antigen (hazard ratio, 1.03; 95% CI, 1.00-1.05; P = 0.037), and Gleason score (>7: hazard ratio, 2.49; 95% CI, 1.25-4.95; P = 0.009). Patients with pathologic 11C-choline uptake in the prostatic bed or in pelvic or retroperitoneal lymph nodes had longer PCaspecific survival (median, 12.1 y; 95% CI, 10.5-13.7 y) in comparison to patients with pathologic tracer uptake in the skeleton (median, 9.9 y; 95% CI, 6.8-13.1 y) (log-rank: x2 = 6.5, P < 0.010). Two internally validated nomograms predicted 10- and 15-y PCa-specific survival probability with an accuracy of 76% and 74%, respectively. In an ancillary analysis, we also showed that 11C-choline PET/CT predicts PCa-specific survival after PET/CT, with similar statistical power. Conclusion: 11C-choline PET/CT predicts PCa-specific survival in PCa patients treated with radical prostatectomy who develop biochemical failure during androgen-deprivation therapy. If independent or multicenter confirmation of these findings is obtained, 11Ccholine PET/CT might be more widely used in the follow-up of PCa patients for tailoring salvage therapy. Copyright © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Background: Little is known about the impact of adjuvant radiation therapy (aRT) after radical prostatectomy (RP) on urinary continence (UC). Objective: To evaluate the impact of aRT on UC recovery in patients with unfavourable pathologic characteristics. Design, setting, and participants: The study included 361 patients with either pT2 with positive surgical margin(s) or pT3a/pT3b node-negative disease treated with RP at a tertiary care referral centre. Intervention: Patients were stratified according to the administration of aRT into two groups: group 1 (no aRT; n = 208; 57.8%) and group 2 (aRT; n = 153; 42.2%). Outcome measurements and statistical analysis: Continence was defined as no use of protective pads. Log-rank test was used to compare the rate of UC recovery according to aRT status. The association between aRT and UC was also tested in Cox regression models after accounting for age, Cancer of the Prostate Risk Assessment (CAPRA) score, nerve-sparing (NS) status, Charlson Comorbidity Index, body mass index, and year of surgery. Results and limitations: At a mean follow-up of 30 mo, 254 patients (70.4%) recovered complete UC. The 1-and 3-yr UC recovery was 51% and 59% for patients submitted to aRT versus 81% and 87% for patients not receiving aRT, respectively (p < 0.001). At univariable analysis, older age (p < 0.001), presence of non-organ-confined disease (p < 0.001), non-NS procedure (p < 0.001), and delivery of aRT (p < 0.001) were significantly associated with lower UC. At multivariable analysis, the delivery of aRT remained an independent predictor of worse UC recovery (hazard ratio: 0.57; p = 0.001). Patients treated with aRT had a 1.6-fold higher risk of incontinence. Younger age (p = 0.02), lower CAPRA score (p = 0.03), and NS approach (p < 0.001) also represented independent predictors of UC recovery. The main limitations of the study are related to the lack of validated questionnaires in the evaluation of UC and in the lack of information regarding UC status at aRT. Conclusions: The delivery of aRT has a detrimental effect on UC. The oncologic benefits must be balanced with an impaired UC recovery. Patients should be informed of such impairment before adjuvant treatments are planned. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Background: According to the TNM staging system, patients with prostate cancer (PCa) with lymph node invasion (LNI) are considered a single-risk group. However, not all LNI patients share the same cancer control outcomes. Objective: To develop and internally validate novel nomograms predicting cancerspecific mortality (CSM)-free rate in pN1 patients. Design, setting, and participants: We evaluated 1107 patients with pN1 PCa treated with radical prostatectomy, pelvic lymph node dissection, and adjuvant therapy at two tertiary care centers between 1988 and 2010. Outcome measurements and statistical analysis: Univariable and multivariable Cox regression models tested the relationship between CSM and patient clinical and pathologic characteristics, which consisted of prostate-specific antigen (PSA) value, pathologic Gleason score, pathologic tumor stage, status of surgical margins, number of positive lymph nodes, and status of adjuvant therapy. A Cox regression coefficient-based nomogram was developed and internally validated. Results and limitations: All 1107 patients received adjuvant hormonal therapy (aHT). Additionally, 35% of patients received adjuvant radiotherapy (aRT). The 10-yr CSM-free rate was 84% in the entire cohort and 87% in patients treated with aRT plus aHT versus 82% in patients treated with aHT alone (p = 0.08). At multivariable analyses, PSA value, pathologic Gleason score, pathologic tumor stage, surgical margin status, number of positive lymph nodes, and aRT status were statistically significant predictors of CSM (all p

Introduction: The European Association of Urology (EAU) guidelines recommend to perform extended pelvic lymph node dissection (ePLND) in all patients with a risk of lymph node invasion (LNI) higher than 5% estimated by the updated Briganti nomogram. However, this model has been developed in patients exclusively treated with open radical prostatectomy. No study has specifically assessed the accuracy of this model among men treated with robot-assisted radical prostatectomy (RARP). We hypothesized that EAU indications for PLND are accurate also among patients treated with RARP. Materials and Methods: We evaluated 615 patients treated with RARP and PLND between 2006 and 2012 at a single tertiary referral center. The predictive accuracy of the nomogram was quantified using the receiver operating characteristic-derived area under the curve, the calibration plot method, and decision curve analyses. Results: Median of lymph nodes (LNs) removed was 9 (interquartile range: 6-13). The rate of LNI was 5%. External validation of the Briganti nomogram showed good accuracy (81.8%). A nomogram-derived cutoff of 5% would allow the avoidance of 75% of PLND at the cost of missing of 19.4% of patients with LNI. When the same analyses were repeated in men with at least 10 and 15 LNs removed, the 5% cutoff was associated with a reduction in PLND and with an LNI missing rates of 67.6% and 59.3% and 17.4% and 6.2%, respectively. Similarly, the prediction accuracy increased to 81.2% and 85.3%, respectively. The decision curve analysis showed an increase in the net-benefit in the prediction range between 2.5% and 54%. Conclusions: We report the first validation of the EAU guideline recommendation for PLND among patients exclusively treated with RARP. We demonstrated that the accuracy of Briganti nomogram is high, but the proposed 5% cutoff is valid only in the presence of adequate ePLND. © Copyright 2014, Mary Ann Liebert, Inc. 2014.

It is well known that the administration of phosphodiesterase type-5 inhibitors (PDE5-Is) may improve erectile function (EF) recovery after bilateral nerve-sparing radical prostatectomy (BNSRP). The aim of our study was to identify predictors of the use of a high number of PDE5-Is (one or more per week) after surgery among 184 patients taking proerectile medications on demand. At a mean follow-up of 22.7 months, 116 patients (63%) recovered EF. Overall, EF recovery rates at 1- and 2- year follow-up were 47.3% and 65.4%, respectively. Overall, 43 (23.4%) patients used one or more PDE5-Is per week. Preoperative EF was the only predictor of the use of one or more PDE5-Is per week after BNSRP. This held true even after adjusting our analyses for age at surgery, body mass index and EF at 1 month after surgery. Particularly, patients fully potent before surgery had roughly 2.1-fold higher probability of using one or more pills per week compared with their counterparts with some degree of preoperative erectile dysfunction (ED; odds ratio: 2.16; 95% confidence interval: 1.03-4.37). In conclusion, preoperative EF represents the only determinant of the use of a higher number of PDE5-Is after surgery. Patients with better preoperative EF might represent individuals more motivated to achieve satisfactory sexual function after surgery. These observations should provide physicians with better preoperative patient counseling and management of postoperative ED.

The ability to identify prostate cancer patients at 'high risk' for bone metastasis development could allow early selection of those most likely to benefit from interventions to prevent or delay bone metastasis. This review is aimed to identify potential predictors of risk for bone metastasis in newly diagnosed patients and in those who have already received treatment. At diagnosis, established predictors of prostate cancer aggressiveness (e.g. PSA level, clinical stage, Gleason score) can identify patients at risk for bone metastasis. Following treatment of the disease, increasing evidence suggests that absolute PSA levels and other measures of PSA kinetics are useful to aid prediction of bone metastasis risk in patients both with and without a history of ADT. However, which PSA parameter most accurately predicts risk and the cut-off values that should be employed are unclear. Inclusion of PSA parameters to identify a high risk population may be beneficial in whom bone-modifying treatments are being considered. Other novel (but unvalidated) biomarkers that potentially predict the development of bone metastases have been identified, although it is unclear whether they will have value as independent markers or when combined with other parameters (e.g. measures of PSA kinetics). Further prospective studies of PSA kinetics and other predictive markers are, therefore, required to define the optimal criteria for identifying patients at high risk of bone metastases and those who are most likely to benefit from intensive monitoring and therapeutic intervention. (C) 2013 Elsevier Ltd. All rights reserved.

Purpose The role of adjuvant radiotherapy (aRT) in treating patients with pN1 prostate cancer is controversial. We tested the hypothesis that the impact of aRT on cancer-specific mortality (CSM) in these individuals is related to tumor characteristics. Methods We evaluated 1,107 patients with pN1 prostate cancer treated with radical prostatectomy and anatomically extended pelvic lymph node dissection between 1988 and 2010 at two tertiary care centers. All patients received adjuvant hormonal therapy with or without aRT. Regression tree analysis stratified patients into risk groups on the basis of their tumor characteristics and the corresponding CSM rate. Cox regression analysis tested the relationship between aRT and CSM rate, as well as overall mortality (OM) rate in each risk group separately. Results Overall, 35% of patients received aRT. At multivariable analysis, aRT was associated with more favorable CSM rate (hazard ratio [HR], 0.37; P < .001). However, when patients were stratified into risk groups, only two groups of men benefited from aRT: (1) patients with positive lymph node (PLN) count ≤ 2, Gleason score 7 to 10, pT3b/pT4 stage, or positive surgical margins (HR, 0.30; P = .002); and (2) patients with PLN count of 3 to 4 (HR, 0.21; P = .02), regardless of other tumor characteristics. These results were confirmed when OM was examined as an end point. Conclusion The beneficial impact of aRT on survival in patients with pN1 prostate cancer is highly influenced by tumor characteristics. Men with low-volume nodal disease (≤ two PLNs) in the presence of intermediate- to high-grade, non–specimen-confined disease and those with intermediate-volume nodal disease (three to four PLNs) represent the ideal candidates for aRT after surgery.

BACKGROUND: During the last years, there has been a rapid adoption of intensity-modulated radiation therapy (IMRT) in patients with prostate cancer (PCa), despite the lack of randomized trials evaluating its effectiveness. The aim of our study was to evaluate the survival benefit associated with IMRT in patients with PCa.PATIENTS AND METHODS: Overall, 42 483 patients with PCa treated with IMRT or initial observation between 2001 and 2007 within the Surveillance, Epidemiology, and End Results (SEER)-Medicare were evaluated. Patients in both treatment arms were matched using propensity-score methodology. After propensity-score matching, 19 064 patients remained in our analyses. Eight-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 8-year CSM rates were 3.4% and 4.1% for patients treated with IMRT versus initial observation, respectively (P < 0.001). The corresponding 8-year NNT was 142. In patients with low/intermediate-risk disease, IMRT was not associated with lower CSM rates compared with observation (P = 0.7). In patients with high-risk disease, the 8-year CSM rates for IMRT versus observation were 5.8% versus 10.5%, respectively (P < 0.001). The corresponding NNT was 21. When high-risk patients were stratified according to age (1) the 8-year CSM rates for IMRT versus observation were 4.3% versus 9.4% and 6.9% versus 11.9% and 5.3% versus 11.4% and 6.1% versus 10.1%, respectively (all Ps < 0.001). The corresponding NNTs were 19, 21, 16, and 25, respectively. In multivariate analyses, the protective effect of IMRT was more evident in high-risk patients with younger age and lower comorbidities.CONCLUSIONS: IMRT leads to a survival advantage only in patients with high-risk disease. Conversely, patients with low/intermediate-risk disease did not benefit from IMRT at 8-year follow-up.

Introduction: In surgically treated patients with renal cell carcinoma (RCC), the progression-free survival (PFS) rate may significantly change according to the progression-free postoperative period. To test this hypothesis, we set to evaluate the conditional PFS rate in surgically treated patients with RCC. Methods: We evaluated 1,454 patients with RCC, surgically treated between 1987 and 2010, at a single institution. Cumulative survival estimates were used to generate conditional PFS rates. Separate Cox regression models were fitted to predict clinical-progression risk in patients who were progression free from 1 to 10 years after surgery. Results: During the immediate postoperative period, the 5-year PFS rate was 88%, and it increased to 92%, 94%, and 97% in patients who remained progression free at, respectively, 1, 5, and 10 years after surgery. At multivariable analyses, where patients with stage I disease were considered as a reference, the highest clinical-progression risk was observed at the eighth postoperative year in patients with stage II disease (hazard ratio [HR]: 2.9) and during the immediate postoperative period in patients with stage III to IV disease (HR: 5.5). In comparison with patients with grade I disease, the highest clinical-progression risk was observed at the fourth (as well as eighth) postoperative year in patients with grade II disease (HR: 5.7), sixth postoperative year in patients with grade III disease (HR: 7.2), and during the immediate postoperative period in patients with grade IV disease (HR: 8.5). Conclusions: The postoperative progression-free period has an important effect on the subsequent clinical-progression risk. This aspect should be considered along with tumor characteristics to plan the most cost-effective follow-up scheme for surgically treated patients with RCC. © 2014 Elsevier Inc.

Objective To assess whether the number of cores at first prostate biopsy affect pathologic findings at radical prostatectomy (RP) in potential candidates for active surveillance (AS). Material and Methods Two hundred seventy-five patients fulfilling Prostate Cancer Research International: Active Surveillance criteria (prostate-specific antigen level ≤10 ng/mL, prostate-specific antigen density

Background Although therapeutic guidelines recommend the use of neoadjuvant chemotherapy before radical cystectomy (RC) in patients who have muscle-invasive bladder cancer (MIBC), this approach remains largely underused. One of the main reasons for this phenomenon might reside in concerns regarding the risk of morbidity and mortality associated with neoadjuvant chemotherapy. Objective To compare perioperative outcomes between patients receiving neoadjuvant chemotherapy and those treated with RC alone. Design, setting, and participants Relying on the Surveillance Epidemiology and End Results-Medicare-linked database, 3760 patients diagnosed with MIBC between 2000 and 2009 were evaluated. Intervention RC alone or RC plus neoadjuvant chemotherapy. Outcome measurements and statistical analysis Complications occurred within 30 and 90 d after surgery. Heterologous blood transfusions (HBTs), length of stay (LoS), readmission, and perioperative mortality were compared. To decrease the effect of unmeasured confounders associated with treatment selection, propensity score-matched analyses were performed. Results and limitations Overall, 416 (11.1%) of patients received neoadjuvant chemotherapy. Following propensity score matching, 416 (20%) and 1664 (80%) patients treated with RC plus neoadjuvant chemotherapy and RC alone remained, respectively. The 30-d complication, readmission, and mortality rates were 66.0%, 32.2%, and 5.3%, respectively. The 90-d complication, readmission, and mortality rates were 72.5%, 46.6%, and 8.2%, respectively. When patients were stratified according to neoadjuvant chemotherapy status, no significant differences were observed in the rates of complications, HBT, prolonged LoS, readmission, and mortality between the two groups (all p ≥ 0.1). These results were confirmed in multivariate analyses, where the use of neoadjuvant chemotherapy was not associated with higher risk of 30- and 90-d complications, HBT, prolonged LoS, readmission, and mortality (all p ≥ 0.1). Our study is limited by its retrospective nature. Conclusions The use of neoadjuvant chemotherapy is not associated with higher perioperative morbidity or mortality. These results should encourage wider use of neoadjuvant chemotherapy when clinically indicated. Patient summary Chemotherapy before radical cystectomy in patients with muscle-invasive bladder cancer does not increase the risk of complications or death. The use of chemotherapy should be strongly encouraged, as recommended by clinical guidelines, given its benefits. © 2014 European Association of Urology.

Context Prostate cancer (PCa) patients with isolated clinical lymph node (LN) relapse, limited to the regional and/or retroperitoneal LNs, may represent a distinct group of patients who have a more favorable outcome than men with progression to the bone or to other visceral organs. Some data indirectly denote a beneficial impact of pelvic LN dissection on survival in these patients. Objective To provide an overview of the currently available literature regarding salvage LN dissection (SLND) in PCa patients with clinical relapse limited to LNs after radical prostatectomy (RP). Evidence acquisition A systematic literature search was conducted using the Medline, Embase, and Web of Science databases to identify original articles, review articles, and editorials regarding SLND. Articles published between 2000 and 2012 were reviewed and selected with the consensus of all the authors. Evidence synthesis Contemporary imaging techniques, such as 11C-choline positron emission tomography and diffusion-weighted magnetic resonance imaging, appear to enhance the accuracy in identifying LN relapse in patients with biochemical recurrence (BCR) and after RP. In these individuals, SLND can be considered as a treatment option. The currently available data suggest that SLND can delay clinical progression and postpone hormonal therapy in almost one-third of the patients, although the majority will have BCR. An accurate and attentive preoperative patient selection may help improve these outcomes. The most frequent complication after SLND was lymphorrhea (15.3%), followed by fever (14.5%) and ileus (11.2%). It is noteworthy that all examined cohorts originated from retrospective single-institution series, with limited sample size and short follow-up. Consequently, the current findings cannot be generalized and warrant further investigation in future prospective trials. Conclusions The current data suggest that SLND represents an option in patients with disease relapse limited to the LNs after RP; however, more robust data derived from well-designed clinical trials are needed to validate the role of SLND in this selected patient population. Patient summary Salvage lymph node dissection (SLND) represents a treatment option in for patients with prostate cancer relapse limited to the lymph nodes; however, more robust data derived from well-designed clinical trials are needed to validate the role of SLND in this selected patient population.

Introduction Previous series during the dissemination era of minimally invasive techniques for treatment of prostate cancer (PCa) showed a declining use of pelvic lymph node dissection (PLND). The aim of our study was to re-assess the impact of robot-assisted radical prostatectomy (RARP) on the utilization rate of PLND and its extent in the post-dissemination period. Methods Relying on the Surveillance Epidemiology and End Results (SEER) Medicare-linked database, 5804 patients with non-metastatic PCa undergoing open radical prostatectomy (ORP) or RARP between years 2008 and 2009 were identified. Uni- and multivariable logistic regression analyses tested the relationship between surgical approach (RARP vs. ORP) and: 1 - the rate of PLND (pNx vs. pN0-1); and 2 - the extent of PLND (limited vs. extended). Results Overall, 3357 (57.8%) patients underwent a PLND. The proportion of patients treated with PLND was significantly higher among ORP vs. RARP patients: 71.2 vs. 48.6%, respectively (P < 0.001). In addition, the median number of lymph nodes removed was significantly higher for patients treated with ORP vs. RARP: 5 vs. 4, respectively (P < 0.001). In multivariable analyses, ORP was associated with 2.7- and 1.3-fold higher odds of undergoing PLND and of receiving an extended PLND compared to RARP, respectively (both P ≤ 0.001). Stratified analyses according to disease risk classifications revealed similar trends. Conclusions In the post-dissemination era, RARP remains associated with a decreased use of PLND and suboptimum extent. Efforts should be made to improve guideline adherence in performing a PLND whenever indicated according to tumor aggressiveness, despite surgical approach. © 2014 Published by Elsevier Ltd. All rights reserved.

The optimal treatment of men with positive lymph nodes after radical prostatectomy (RP) is an active debate in the urologic community. In addition, this topic has seemed to gain scientific attention in recent years because of the shift to offering RP to higher risk patients. However, patients with positive lymph nodes represent a paradigmatic group for which indications for and typesof treatmenthavebeenbased mainly on eminence-based rather than on evidence-based medicine. In the past, these patients were generally not considered suitable for radical treatment because of the assumption that cure was neither possible nor helpful. For several years, any definitive therapy attempt was denied because of undisputed dogma: Patients with lymph node metastasis are affected by a systemic disease. This assumption led to threemisguided concepts in clinical practice. First, maximizing local control was considered either useless or of limited therapeutic value. Second, extending the template of pelvic lymph node dissection (PLND) was not justified because, according to opponents of such an extensive approach, these patients would progress anyway, regardless of the extent of PLND. Third, patients with positive lymph nodes needed lifelong adjuvant androgen-deprivation therapy because of the presence of disseminated disease. Such statements can certainly be challenged today. We should still understand whether the presence of pelvic lymph node metastases indicates systemic dissemination. The etymology of the term metastasis shows that it comes from the Greek terms meta-, meaning across, and histanai, meaning to place. Therefore, the terms indicate a tumor spread outside of the organ of origin. For this reason, strictly speaking, patients with lymph node invasion have metastatic disease. However, such statement should be balanced by several key and still unknown aspects of the metastasizing process of prostate cancer (PCa). Cancer cells that spread to the lymph nodes have acquired certain phenotypic changes that confer to them the ability to invade lymphatic vessels and access lymph nodes; however, we still do not know what happens next. Lymph nodes can represent the door to hematogenous dissemination to other organs [1]. Tumor cells could spread from lymph nodes to distant organs via blood vessels associated with the nodes or by entering the venous system via the major lymphatic ducts and then spreading via blood vessels. In mice with metastatic lymph nodes, the expression of lymphangiogenesis signals the increased probability of metastasization to additional organs [2]. However, in some cases, these draining lymph nodes may also represent dead ends rather than temporary stopping points from which more distant metastases are launched [3]. Moreover, as demonstrated in breast cancer, these cells may have specific epigenetic modifications that predispose to selective metastasization to the lymph nodes instead of visceral organs [4]. Therefore, the routes of systemic and nodal metastasization may also be different and separated. Cancer metastasized to the lymph nodes can also enter a quiescent state. This status is well known as tumor dormancy [5]. Tumor dormancy ensues when cancer cell proliferation is counteracted by other mechanisms such as apoptosis because of impaired vascularization or immunosurveillance, and cellular dormancy ensues when growth of the cancer cells is arrested. Several mechanisms can explain tumor dormancy, including disruption of crosstalk between EURO P E AN URO L OG Y 6 5 ( 2 0 1 4 ) 2 6 – 2 9

Purpose: We performed a head-to-head comparison of the PHI (Prostate Health Index) and PCA3. Materials and Methods: We evaluated PHI and PCA3 performance in 211 patients undergoing initial (116) or repeat (95) prostate biopsy. Multivariable logistic regression analysis was done using the AUC to test the accuracy of PHI and PCA3 for predicting prostate cancer in the overall population and in each setting. Decision curve analysis was used to compare the clinical benefit of different models. Results: Overall, the AUC of the PHI (0.70) was significantly higher than the AUC of PCA3 (0.59), total prostate specific antigen (0.56) and free-to-total prostate specific antigen (0.60) (p = 0.043, 0.002 and 0.037, respectively). PHI was more accurate than PCA3 for predicting prostate cancer in the initial setting (AUC 0.69 vs 0.57) and in the repeat setting (AUC 0.72 vs 0.63), although no statistically significant difference was observed. Including PCA3 in the base multivariable model (prostate specific antigen plus free-to-total prostate specific antigen plus prostate volume) did not increase predictive accuracy in either setting (AUC 0.79 vs 0.80 and 0.75 vs 0.76, respectively). Conversely, including PHI in the base multivariable model improved predictive accuracy by 5% (AUC 0.79 to 0.84) and 6% (AUC 0.75 to 0.81) in the initial and repeat prostate biopsy settings, respectively. On decision curve analysis the highest net benefit was observed when PHI was added to the base multivariable model. Conclusions: PHI and PCA3 provide a significant increase in sensitivity and specificity compared to all other examined markers and they may help guide biopsy decisions. PCA3 does not increase the accuracy of predicting prostate cancer when PHI is assessed.

Objective Positron emission tomography (PET)/computed tomography (CT) has been shown to be a valid tool in detecting lymph node (LN) metastases in men with biochemical recurrence after radical prostatectomy. We assessed its validity in detecting a single positive LN at pathologic examination in regard to an increasing interest in lesion-targeted salvage therapies. Methods and materials We included 46 patients with biochemical recurrence after radical prostatectomy and a single positive spot at [ 11 C]choline PET/CT who underwent pelvic or pelvic and retroperitoneal LN dissection. The ability of [ 11 C]choline PET/CT in identifying the exact positive LN was assessed with the positive predictive value (PPV) in the overall population and according to androgen deprivation therapy, prostate-specific antigen value, and site of PET/CT positivity. Results Overall, 30 patients (65%) had positive LNs at pathologic examination. Of these, only 16 (35%) had pathologically confirmed metastases in the same lymphatic region and 11 (24%) had involvement of 1 single LN. Conversely, 28 patients had positive LNs in other areas and 8 had no evidence of metastases. The overall PPV of PET/CT was 34.8% and 23.9% when exact concordance was defined according to the lymphatic landing site and single positive LN, respectively. The PPV ranged from 33.3% to 44.4% and from 17.9% to 28.6%, in men with and without androgen deprivation therapy, respectively. Conclusions The PPV [ 11 C]choline of PET/CT in correctly identifying patients with a single positive LN at salvage LN dissection is poor (24%). Therefore, extensive salvage treatment approaches are needed to maximize the chance of cure.

Background: The risk of in-hospital mortality after cytoreductive nephrectomy (CNT) is non-negligible and may vary widely according to various patient and hospital characteristics and clinical contexts. Objective: To better elucidate the mechanisms underlying variability in operative mortality after CNT. Design, setting, and patients: Using the US-based Nationwide Inpatient Sample registry, a weighted estimate of 16 285 patients with metastatic renal cell carcinoma (mRCC) treated with CNT between 1998 and 2007 was made retrospectively. Outcome measurements and statistical analysis: Failure to rescue (FTR), defined as the number of deaths in patients who developed an adverse outcome during hospitalization. Univariable and multivariable logistic regression models were used. Results: Of all 16 285 mRCC patients who underwent a CNT, 31% had an occurrence of one complication or more. The overall FTR rate was 5% and differed significantly according to age (75 yr vs = 3 vs 0: 7.7% vs 4.8%), as well as hospital bed size (small vs large: 7.2% vs 5.3%, all p

Purpose: Patients with a single microfocus of prostate cancer at initial biopsy represent the ideal candidates for active surveillance. We investigate whether the number of cores taken affects the concordance rate between microfocus of prostate cancer and the confirmation of a pathologically insignificant prostate cancer at radical prostatectomy. Materials and Methods: Data were analyzed from 233 patients with a single microfocus of prostate cancer at initial transrectal prostate biopsy (a single focus of Gleason 6 involving 5% or less of the core) subsequently treated with radical prostatectomy. The chi-square test, cubic spline analyses and logistic regression analyses were used to depict the relationship between the number of cores taken and the probability of confirming the presence of an indolent disease (pathologically confirmed insignificant prostate cancer defined as radical prostatectomy Gleason score 6 or less, tumor volume 0.5 ml or less and organ confined disease). Results: Overall 65 patients (27.9%) showed pathologically confirmed insignificant prostate cancer at radical prostatectomy. The rate of pathologically confirmed insignificant prostate cancer was 3.8%, 29.6% and 39.4% in patients who underwent biopsy of 12 or fewer cores, 13 to 18 cores and 19 or more cores, respectively (p < 0.001). After adjusting for the available confounders, age (p = 0.04), number of cores taken (p < 0.001) and prostate specific antigen density (p < 0.02) were independent predictors of pathologically confirmed insignificant prostate cancer. Conclusions: Of patients diagnosed with a single microfocus of prostate cancer the number of biopsy cores taken was a major independent predictor of having pathologically confirmed insignificant prostate cancer at radical prostatectomy. Therefore, when active surveillance is considered as a possible alternative in patients with microfocus of prostate cancer, the number of cores taken should be taken into account in decision making.