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To assess the impact of statin use on outcomes of patients with non-muscle-invasive bladder cancer (NMIBC). To measure the effect of statin use on the efficacy of intravesical bacillus Calmette-Guérin (BCG) therapy.A retrospective analysis was performed on 1117 patients treated with transurethral resection of the bladder (TURB) for NMIBC at three institutions between 1996 and 2007. Statin use at the time of diagnosis was recorded for each patient. Univariable Cox regression models addressed the association of statin use with disease recurrence, disease progression, cancer-specific mortality and overall mortality in all patients, patients with primary NMIBC, patients not treated with BCG, and patients treated with BCG.Overall, 341 patients (30.5%) used statins and 776 (69.5%) did not. Within a median (interquartile range) follow-up of 62.7 (25.0-110.7) months, 469 patients (42.0%) experienced disease recurrence, 103 (9.2%) progression, 50 (4.5%) cancer-specific mortality, and 299 (26.8%) any-cause mortality. In univariable Cox regression analyses, statin use was not associated with any of these four endpoints (P0.05 for all). In subgroup analyses, statin use was also not associated with prognosis in patients with primary NMIBC or patients not receiving BCG (P0.05 for all four endpoints). Statin use was not associated with response to BCG (P0.05 for all four endpoints).Statin users did not experience different outcomes compared with non-users and statin use did not affect the efficacy of BCG immunotherapy; these data do not support modification or discontinuation of statin therapy for patients with NMIBC.

What's known on the subject? and what does the study add?: Radical nephroureterectomy (RNU), the standard of care treatment for high-risk urothelial carcinoma of the upper tract (UTUC), results in loss of a renal unit. Loss of renal function decreases eligibility for systemic chemotherapies and results in decreased overall survival in various malignancies. The study shows that only a small proportion of patients had a preoperative renal function that would allow cisplatin-based chemotherapy. Moreover, eGFR significantly decreased after RNU, thereby lowering the rate of cisplatin eligibility to only 16 and 52% of patients based on the thresholds of 60 and 45 mL/min/1.73 m(2) , respectively. Taken together with the rest of the literature, the findings of the study support the use of cisplatin-based chemotherapy, when indicated, in the neoadjuvant rather than adjuvant setting.To report (i) the estimated glomerular filtration rate (eGFR) changes in patients undergoing radical nephro-ureterectomy (RNU) for upper tract urothelial carcinoma (UTUC); (ii) the rate of change in eGFR in patients eligible for cisplatin-based chemotherapy; and (iii) the association of preoperative, postoperative and rate of change of renal function variables with survival outcomes.We performed a retrospective analysis of 666 patients treated with RNU for UTUC at seven international institutions from 1994 to 2007. The eGFR was calculated at baseline and at 3-6 months (Modification of Diet in Renal Disease formula (MDRD) and Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EP) equations).The median (interquartile range) eGFR decreased by 18.2 (8-12)% after RNU. A total of 37% of patients had a preoperative eGFR ≥ 60 mL/min/1.73 m(2) , which decreased to 16% after RNU (P0.001); 72% of patients had a preoperative eGFR ≥ 45 mL/min/1.73 m(2) , which decreased to 52% after RNU (P0.001). The distributions were similar when analyses were restricted to patients with locally advanced disease (pT3-pT4) and/or lymph node metastasis. Patients older than the median age of 70 years were more likely to have a decrease in eGFR after RNU (P0.001). None of the renal function variables was associated with clinical outcomes such as disease recurrence, cancer-specific and overall mortality; however, when analyses were restricted to patients who had no adjuvant chemotherapy and did not experience disease recurrence (n = 431), a preoperative eGFR ≥ 60 mL/min/1.73 m(2) (P = 0.03) and a postoperative eGFR ≥ 45 mL/min/1.73 m(2) (P = 0.04) were associated with better overall survival in univariable analyses.In patients who had UTUC, eGFR was low and furthermore, it significantly decreased after RNU. Renal function did not affect cancer-specific outcomes after RNU.

To identify clinicopathological factors that predict outcomes in patients with a single lymph node (LN) metastasis (pN1) treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). LN metastasis is an established predictor of clinical outcomes in patients. While most patients with large LN burden experience disease recurrence, lymphadenectomy can be curative in patients with pN1 disease.We analysed 381 patients with pN1 UCB from a multi-institutional cohort of 4335 patients with UCB treated with RC and lymphadenectomy without preoperative chemo- or radiotherapy. Subgroup analyses were performed for patients with ≥9 LNs removed and according to adjuvant chemotherapy administration (n = 215).The median (interquartile range, IQR) LN number was 15 (19) and the median (IQR) LN density was 6.7 (7.5)%. Within a median follow-up of 41 months, the mean (+/- SD) 2- and 5-year cancer-specific survival (CSS) rates were 55 (3)% and 46 (3)%, respectively. On multivariable analysis that adjusted for the effects of standard clinicopathological features, female gender (hazard ratio [HR] 1.48, P = 0.023), higher tumour stage (HR 1.68, P = 0.007), positive soft tissue surgical margin (STSM; HR 2.06, P = 0.004), higher LN density (HR 2.99, P = 0.025) and absence of adjuvant chemotherapy (HR 0.70, P = 0.026) were independently associated with CSS. In subgroup analyses of patients with ≥9 LNs removed, tumour stage and STSM status remained independent predictors for CSS (P = 0.009 and P0.001, respectively).About half of the patients with pN1 UCB died from UCB within 5 years of RC. Pathological stage and STSM status are strong predictors for outcomes. Accurate prediction of the individual risk of CSS may help risk stratifying pN1 UCB in order to help improve clinical-decision making. Patients with pN1 UCB presenting with additional unfavourable risk factors need a closer follow-up scheduling and might receive adjuvant therapy.

BACKGROUND AND OBJECTIVES: The RECORD-1 trial established the clinical benefit of everolimus in patients with metastatic renal cell carcinoma (mRCC) after failure of initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. The REACT (RAD001 Expanded Access Clinical Trial in RCC) study was initiated to address an unmet medical need by providing everolimus prior to commercial availability, and also to further assess the safety and efficacy of everolimus in patients with VEGFr-TKI-refractory mRCC. PATIENTS AND METHODS: REACT (Clinicaltrials.gov: NCT00655252) was a global, open-label, expanded-access programme in patients with mRCC who were intolerant of, or who had progressed on or after stopping treatment with, any available VEGFr-TKI therapy. Patients received everolimus 10mg once daily, with dose and schedule modifications allowed for toxicity. Patients were closely monitored for the development of serious and grades 3/4 adverse events (AEs). Response was assessed by RECIST every 3months for the first year and every 6months thereafter. RESULTS: A total of 1367 patients were enroled. Safety findings and tumour responses were consistent with those observed in RECORD-1, with no new safety issues identified. The most commonly reported serious AEs were dyspnoea (5.0%), pneumonia (4.7%) and anaemia (4.1%), and the most commonly reported grades 3/4 AEs were anaemia (13.4%), fatigue (6.7%) and dyspnoea (6.5%). Best overall response was stable disease in 51.6% and partial response in 1.7% of patients. Median everolimus treatment duration was 14weeks. CONCLUSION: Everolimus is well tolerated in patients with mRCC and demonstrates a favourable risk-benefit ratio.

• To compare oncological outcomes in patients undergoing open radical nephroureterectomy (ONU) with those in patients undergoing laparoscopic radical nephroureterectomy (LNU).• A total of 773 patients underwent radical nephroureterectomy at nine centres worldwide; 703 patients underwent ONU and 70 underwent LNU. • Demographic, perioperative and oncological outcome data were collected retrospectively. • Statistical analysis of data was performed using chi-squared, Mann-Whitney U- and log-rank tests, and Cox regression analyses. • The median (interquartile range) follow-up for the cohort was 34 (15-65) months.• The two groups were well matched for tumour stage, presence of lymphovascular invasion (LVI) and concomitant carcinoma in situ (CIS). • There were more high-grade tumours (77.1% vs. 56.3%; P0.001) but fewer lymph node positive patients (2.9% vs. 6.8%; P= 0.041) in the LNU group. • Estimated 5-year recurrence-free survival (RFS) was 73.7% and 63.4% for the ONU and LNU groups, respectively (P= 0.124) and estimated 5-year cancer-specific survival (CSS) was 75.4% and 75.2% for the ONU and LNU groups, respectively (P= 0.897). • On multivariable analyses, which included age, gender, race, previous endoscopic treatment for bladder cancer, technique for distal ureter management, tumour location, pathological stage, grade, lymph node status, LVI and concomitant CIS, the procedure type (LNU vs. ONU) was not predictive of RFS (Hazard ratio [HR] 0.80; P= 0.534) or CSS (HR 0.96; P= 0.907).• The present study is the second large, independent, multicentre cohort to show oncological equivalence between ONU and LNU for well selected patients with upper urinary tract urothelial cancer, and the first to suggest parity for the techniques in patients with unfavourable disease.

Background: Relatively few studies investigated the importance of frailty in radical cystectomy (RC) patients. We tested the ability of frailty, using the Johns Hopkins Adjusted Clinical Groups indicator, to predict early perioperative outcomes after RC. Methods: RC patients were identified within the National Inpatient Sample database (2000–2015). The effect of frailty, age and Charlson Comorbidity Index were tested in five separate multivariable models predicting: (1) complications, (2) failure to rescue (FTR), (3) in-hospital mortality, (4) length of stay (LOS) and (5) total hospital charges (THCs). All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics. Results: Of 23,967 RC patients, 5833 (24.3%) were frail, 7721 (32.2%) were aged ≥75 years and 2832 (11.8%) had CCI ≥2. Frailty, age ≥75 years and CCI ≥2 were non-overlapping in 86.3% of the cohort. Any two or three of these features were recorded in 12.4 and 1.3%, respectively. Frailty was an independent predictor of all five examined endpoints and the magnitude of its association was stronger or at least equal than that of age ≥75 years and CCI ≥2. Conclusion: Frailty, advanced age and comorbidities represent non-overlapping patients’ characteristics. Of those, frailty represents the most consistent and strongest predictor of early adverse outcomes after RC. Ideally, all three indicators should be considered in retrospective, as well as prospective analyses. Pre-surgical recognition of frail patients should be ideally incorporate in clinical practice in order to address these patients to multimodal pre-habilitation programs that may potentially improve the perioperative prognosis.

Background: Pathological stage and grade of renal pelvis urothelial carcinoma (RPUC) are difficult to estimate before radical nephroureterectomy (RNU). Objective: To examine tumor size as an independent predictor of muscle-invasive and/or non–organ-confined rates of RPUC at RNU. Design, setting, and participants: Within the Surveillance, Epidemiology and End Results (SEER) database (2004–2016), we identified nonmetastatic RPUC at RNU. Outcome measurements and statistical analysis: First, we examined stage and grade distributions. Second, two separate univariable and subsequent multivariable logistic regression models (LRMs) were fitted to test the association between tumor size and the rate of (1) muscle-invasive or higher (pT2–4N0–2) and (2) non–organ-confined (pT3–4N0–2) RPUC at RNU. Results and limitations: Of 4657 patients, 3052 (65.5%) had pT2–4N0–2 and 2382 (51.2%) pT3–4N0–2 RPUC at RNU. The median tumor size was 3.7 cm (interquartile range 2.5–5.0). The high-grade RPUC rate ranged from 71.1% to 87.2% (p < 0.001) among SEER registries. Conversely, no differences were recorded for stage (p > 0.05) or tumor size (p = 0.1) across all registries. Rates of pT2–4N0–2 and pT3–4N0–2 RPUC increased with tumor size. Specifically, for tumor size intervals from 0.1–1.0 cm to 9.1–10.0 cm, the pT2–4N0–2 rate ranged from 45% to 83% and the pT3–4N0–2 rate ranged from 23% to 75%, respectively (both p < 0.001). In multivariable LRMs, tumor size (in 1-cm units) was an independent predictor of pT2–4N0–2 (odds ratio [OR] 1.25; p < 0.001) and pT3–4N0–2 (OR 1.30; p < 0.001) disease at RNU. Conclusions: Tumor size is a key predictor of muscle-invasive or non–organ-confined RPUC. Greater tumor size directly and virtually linearly predicts a higher rate of invasive or non–organ-confined RPUC at RNU. Patient summary: For patients with cancer in urinary tract cells lining the kidney, larger tumor size predicts worse stage of the disease at surgery.

Background: Prospective data collection for perioperative outcomes might increase awareness of surgical results obtained for patients with prostate cancer (PCa) undergoing robot-assisted radical prostatectomy (RARP). This would prompt the implementation of measures aimed at reducing the risk of adverse outcomes. Objective: To assess the efficacy of an audit and feedback process aimed at identifying the most common complications after RARP and at implementing measures to improve outcomes. Design, setting, and participants: Overall, 415 patients treated with RARP by a high-volume surgeon were included. Perioperative outcomes for 187 patients treated between September 2016 and December 2017 were prospectively collected at 30 d according to the European Association of Urology guideline recommendations (group 1). An audit and feedback process was implemented in January 2018 whereby the most common complication (anastomotic leak) was identified and measures aimed at improving outcomes (changes in the anastomotic technique) were implemented. The outcomes for group 1 were then compared to 228 patients treated after implementation of the modified surgical technique (group 2). Surgical procedure: A novel technique for posterior reconstruction and urethrovesical anastomosis was introduced. Measurements: Perioperative outcomes included blood loss, operative time, length of stay, and 30-d postoperative complications. Logistic regression models tested the effect of the novel surgical technique on anastomotic leaks. Results and limitations: Overall, 97 patients (23%) experienced postoperative complications at 30 d. The rate of anastomotic leaks was significantly lower in group 2 compared to group 1 (3.1% vs 9.6%; p < 0.01). Similarly, overall and Clavien-Dindo grade ≥2 complication rates were lower in group 2 versus group 1 (17% vs 31%, and 6% vs 20%; both p ≤ 0.001). In multivariable analyses, treatment after implementation of changes in the anastomotic technique independently predicted a lower risk of complications (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.38–0.89) and of anastomotic leaks (OR 0.43, 95% CI 0.17–0.97). The lack of randomization represents the main limitation. Conclusions: Implementation of changes in the urethrovesical anastomosis technique arising from increased awareness of surgical outcomes reduced the risk of anastomotic leaks. These findings highlight the importance of audit and feedback processes using a standardized method for reporting surgical morbidity. Patient summary: Increased awareness of surgical outcomes prompted us to change our technique for connecting the bladder to the urethra during robot-assisted surgery to remove the prostate in patients with prostate cancer. These changes resulted in significant improvements in surgical outcomes.

Background: For patients with nonmetastatic renal cell carcinoma (nmRCC) treated with nephrectomy, prediction of cancer-specific mortality (CSM) by T stage and substage has not been validated for the separate histological subtypes. Objective: To investigate the ability of pathological T stage and substage to predict CSM for patients with clear-cell, papillary, or chromophobe nmRCC treated with nephrectomy. Design, setting, and participants: Using the SEER database for 2004–2016, we identified 87 149 patients with T1–4 N0/X M0 nmRCC treated with nephrectomy for the clear-cell (65 715; 75.4%), papillary (14 587; 16.7%), or chromophobe (6847; 7.9%) histological subtype. Outcome measurements and statistical analysis: Kaplan-Meier plots and Cox regression models were used to estimate CSM. Results and limitations: For all three histological subtypes, patients with T1a–T3a disease exhibited more favorable CSM than patients with T3b–T4 RCC. For clear-cell RCC, there were clinically meaningful and statistically significant differences for virtually all intergroup comparisons among T1a–T3a stages. For papillary T1a–T3a RCC, clinically meaningful differences disappeared, although the statistical significance remained. For chromophobe T1a–T3a RCC, no clinically meaningful or statistically significant differences were observed. For all three histological subtypes, patients with T3b–T4 RCC exhibited virtually uniformly unfavorable CSM, with no clinically meaningful intergroup CSM differences. Conclusion: The use of T stage and substage for stratification of patients with nmRCC treated with nephrectomy revealed differences in CSM among T1a–T3a cases, but not T3b–T4. The magnitude of the CSM difference was greatest for clear-cell, intermediate for papillary, and marginal for chromophobe RCC. Patient summary: For patients with kidney cancer, the stage of their disease assessed after surgery on the affected kidney can predict how likely they are to die from their cancer. This prediction varies for different subtypes of kidney cancer. Stratification of surgically treated patients with nonmetastatic renal cell carcinoma (RCC) by T stage revealed mortality differences among T1a–T3a cases, but not T3b–T4 cases. The magnitude of the differences was greatest for the clear-cell subtype, intermediate for papillary histology, and marginal for chromophobe RCC.

Background Life expectancy (LE) is an important consideration in the clinical decision-making for T1aN0M0 renal cell cancer (RCC) patients. Objective To test the effect of race/ethnicity (Caucasian, African American, Hispanic/Latino, and Asian) on LE predictions from Social Security Administration (SSA) life tables in male and female T1aN0M0 RCC patients. Design, setting, and participants We relied on the Surveillance, Epidemiology, and End Results database. Intervention Radical nephrectomy (RN) and partial nephrectomy (PN). Outcome measurements and statistical analysis Five-year and 10-yr observed overall survival (OS) of pT1aN0M0 RCC patients treated between 2004 and 2006 were compared with the LE predicted from SSA life tables. We repeated the comparison in a more contemporary cohort (2009–2011), with 5-yr follow-up and higher PN rates. Results and limitations In the 2004–2006 cohort, PN rate was 40.7%. OS followed the predicted LE in Caucasians, Hispanics/Latinos, and Asians, but not in African Americans, in whom 5-yr OS rates were 5.0% (male) and 8.7% (female) and 10-yr rates were 4.2% (male) and 11.1% (female) lower than predicted. In the 2009–2011 cohort, PN rate was 59.4%. Same observations were made for OS versus predicted LE in Caucasians, Hispanics/Latinos, and Asians. In African Americans, 5-yr OS rates were 1.5% (male) and 4.9% (female) lower than predicted. Conclusions In RN- or PN-treated pT1aN0M0 RCC patients, LE predictions closely approximated OS of Caucasians, Hispanics/Latinos, and Asians. In African-American patients, SSA life tables overestimated LE, more in females than in males. The limitations of our study are its retrospective nature, its validity for US patients only, and the under-representation of racial/ethnic minorities. Patient summary Social Security Administration life tables can be used to estimate long-term life expectancy in patients who are surgically treated for renal cancer (≤4 cm). However, while for Caucasians, Hispanics/Latinos, and Asians, the prediction performs well, life expectancy of African Americans is generally overestimated by life table predictions. Take Home Message In the clinical decision-making process for T1aN0M0 renal cell cancer patients eligible for radical or partial nephrectomy, the important influence of patient sex and race/ethnicity on life expectancy should be taken into account, when using Social Security Administration life tables.

The best surgical template for salvage pelvic lymph node dissection (sLND) in patients with nodal recurrence from prostate cancer (PCa) after radical prostatectomy (RP) is currently unknown. We analyzed data of 189 patients with a unilateral positive positron emission tomography (PET) scan of the pelvic lymph node areas, who were treated with bilateral pelvic sLND after RP at 11 high-volume centers. The primary endpoint was missed contralateral disease at final pathology, defined as lymph node positive for PCa in the side opposite to the positive spot(s) at the PET scan. Overall, 93 (49%) and 96 (51%) patients received a 11C-choline and a 68Ga prostate-specific membrane antigen (PSMA) PET scan, respectively, and 171 (90%) and 18 (10%) men had one and two positive spots, respectively. The rate of missed contralateral PCa was 18% (34/189), with the rates being 17% (29/171) and 28% (5/18) in men with one and two positive spots, respectively. While the rate of contralateral disease did not differ between 68Ga-PSMA and 11C-choline (29% and 27%, respectively) among men with two positive spots, the rate of contralateral PCa was only 6% with 68Ga-PSMA versus 28% with 11C-choline in patients with a single positive spot. This finding was confirmed at multivariable logistic regression analysis predicting missed disease at final pathology after accounting for confounders (odds ratio: 0.24; p = 0.001). However, in men with a single positive spot at 68Ga-PSMA PET/computed tomography, the rate of single confirmed lymph node metastasis at final pathology was only 33%, suggesting the need for extended template even if unilateral dissection is performed. Awaiting confirmatory studies, patients diagnosed with a single positive spot at the 68Ga-PSMA PET scan might be considered for unilateral extended pelvic sLND. Patient summary We assessed the risk of missing contralateral disease in patients with a positron emission tomography (PET) scan suggestive of unilateral nodal recurrence from prostate cancer (PCa) after radical prostatectomy and who were treated with bilateral salvage lymph node dissection (sLND). Variability exists according to the number of positive spots and PET tracer, with the lowest rate of missed PCa in men diagnosed with a single positive spot at a 68Ga prostate-specific membrane antigen PET scan (6%). If replicated, our data suggest that these patients might be considered for unilateral extended pelvic sLND.

Optimal management of metastatic non-clear cell renal cell carcinoma (non-ccmRCC) remains largely unknown.To test the effect of systemic therapy (ST) and/or cytoreductive nephrectomy (CNT) on overall mortality (OM) in patients with non-ccmRCC.Within the Surveillance, Epidemiology and End Results (SEER) registry (2006-2015), we identified patients with papillary, chromophobe, sarcomatoid, and collecting duct metastatic renal cell carcinoma (mRCC).Temporal trends (estimated annual percentage change [EAPC]), Kaplan-Meier plots, and multivariable Cox regression models were used.Of 1573 patients with non-ccmRCC, 22%, 25%, 25%, and 28% underwent no treatment, ST, CNT, and CNT with ST, respectively. Between 2006 and 2015, rates of CNT and the combination of CNT and ST decreased (EAPC: -6.3% and -3.2%, respectively). Conversely, rates of no treatment and ST increased over time (EAPC: 4.6% and 7.5%, respectively). In multivariable Cox regression models, relative to no treatment, ST (hazard ratio [HR]: 0.5; p0.001), CNT (HR: 0.4; p0.001), and CNT with ST (HR: 0.3; p0.001) were associated with lower OM. Histological subtypes were associated with OM, relative to papillary renal cell carcinoma (RCC): chromophobe (HR: 0.7; p0.01), sarcomatoid (HR: 2.1; p0.001), and collecting duct RCC (HR: 1.9; p0.001). Limitations include the impossibility to stratify patients according to mRCC risk groups.Most non-ccmRCC patients are treated with a combination of CNT and ST or CNT alone or ST alone. The rates of ST alone are increasing. Conversely, the rates of combined CNT and ST and CNT alone are decreasing. These observed temporal patterns of treatment rates are counterintuitive with respect to associated OM benefits, where combination of CNT and ST, as well as CNT alone, resulted in the lowest absolute OM, relative to ST alone, or, even worse, no treatment.We investigated the effect of treatment modalities on survival of patients with metastatic non-clear cell renal cell carcinoma. The combination of cytoreductive nephrectomy and systemic therapy confers greater benefit with respect to single treatments alone.

Objectives: Some patients with localized prostate cancer are at risk of nonobturator lymph node invasion (NOLNI) and may require an extended pelvic lymph node dissection (ePLND). We explored the rate of exclusive NOLNI and developed a nomogram to predict it. Material and methods: We mapped all ePLND specimens according to their anatomic location (obturator, external iliac, internal iliac lymph nodes) and assessed the location-specific rate of LNI in 565 patients. A multivariate logistic regression-based nomogram predicting NOLNI was then internally validated with 200 bootstrap resamples. Results: Overall, 11.1% (63 of 565) had LNI and 21 (3.7%) had exclusive NOLNI. The nomogram predicting exclusive NOLNI was 80.2% accurate. The nomogram's negative predictive value was 99%, when it predicted 0-10% probability of NOLNI. This approach could allow the omission of an ePLND in 350 of 565 (61.9%) patients and still correctly stage 85.8% of NOLNI cases. Conclusions: Our nomogram-based approach offers the possibility of identifying men who are at virtually zero risk of exclusive NOLNI. In these men, an ePLND may be safely avoided. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved. Objectives: Some patients with localized prostate cancer are at risk of nonobturator lymph node invasion (NOLNI) and may require an extended pelvic lymph node dissection (ePLND). We explored the rate of exclusive NOLNI and developed a nomogram to predict it. Material and methods: We mapped all ePLND specimens according to their anatomic location (obturator, external iliac, internal iliac lymph nodes) and assessed the location-specific rate of LNI in 565 patients. A multivariate logistic regression-based nomogram predicting NOLNI was then internally validated with 200 bootstrap resamples. Results: Overall, 11.1% (63 of 565) had LNI and 21 (3.7%) had exclusive NOLNI. The nomogram predicting exclusive NOLNI was 80.2% accurate. The nomogram's negative predictive value was 99%, when it predicted 0-10% probability of NOLNI. This approach could allow the omission of an ePLND in 350 of 565 (61.9%) patients and still correctly stage 85.8% of NOLNI cases. Conclusions: Our nomogram-based approach offers the possibility of identifying men who are at virtually zero risk of exclusive NOLNI. In these men, an ePLND may be safely avoided. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.

PURPOSE: The currently available evidence regarding the prognostic and clinical significance of each variant histology subtype of urothelial bladder cancer remains scarce. We assessed the prognostic value of variant histology in patients with urothelial carcinoma of the bladder treated with radical cystectomy. MATERIALS AND METHODS: PubMed®, Web of Science™, Cochrane Library and Scopus® databases were searched for articles published before October 2019 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. We identified 39 studies comprising 20,544 patients matching our eligibility criteria. RESULTS: Studies were deemed eligible if they compared overall, cancer specific and recurrence-free survival in patients with urothelial carcinoma of the bladder with and without variant histology. Formal meta-analyses were performed for these outcomes. Variant histology was associated with worse cancer specific (pooled HR 1.37, 95% CI 1.24-1.50), overall (pooled HR 1.44, 95% CI 1.26-1.65) and recurrence-free survival (pooled HR 1.32, 95% CI 1.20-1.45). Subgroup analyses demonstrated that "micropapillary" (pooled HR 1.20, 95% CI 1.02-1.41), "plasmacytoid" (pooled HR 2.03, 95% CI 1.17-3.52) and "small cell" variant histology (HR 3.32, 95% CI 1.98-5.59) were also associated with worse overall survival. CONCLUSIONS: Variant histology in patients with urothelial carcinoma of the bladder is associated with increased risks of disease recurrence as well as cancer specific and overall mortality. Variant histology was independently associated with overall survival in the "micropapillary," "plasmacytoid" and "small cell" subgroups. Variant histology should be integrated into prognostic tools to guide risk stratification, treatment planning and patient counseling. However, caution should be exercised in interpreting the conclusions drawn from this study given the limitations, which include the heterogeneity of the population of interest and the retrospective nature of the primary data evaluated.

OBJECTIVE To develop a multivariate nomogram to predict the rate of lymph node invasion (LNI) in patients with clinically localized prostate cancer according to the extent of extended pelvic lymphadenectomy (PLND), which is associated with significantly higher rate of LNI. PATIENTS AND METHODS The study comprised 781 consecutive patients (median age 66.6 years, range 45-85) treated with PLND and radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. Their median ( range) prostate-specific antigen (PSA) level was 7 (1.03-49.91) ng/mL, and their clinical stages were T1c in 433 (55.4%), T2 in 328 (42%) and T3 in 20 (2.6%). Biopsy Gleason sums were

Background: The NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer recommend active surveillance as an option for initial management of T1a 0- to 2-cm renal lesions, in addition to partial nephrectomy, radical nephrectomy, and focal ablation. However, contemporary data regarding the distribution of patient and renal cell carcinoma characteristics within this special patient group are scarce. Methods: Within the SEER database (2002–2016), 13,364 patients with T1aNanyMany 0- to 2-cm renal lesions treated with nephrectomy were identified. Data were tabulated according to histologic subtype, Fuhrman grade (FG1–2 vs FG3–4), age category, and sex. In addition, rates of synchronous metastases were quantified. Results: Overall, clear-cell (69.3%), papillary (21.4%), chromophobe (6.9%), multilocular cystic (2.0%), sarcomatoid dedifferentiation (0.2%), and collecting-duct histologic subtypes (0.2%) were identified. Advanced age was associated with a lower rate of FG1–2 clear cell histologic subtype (70.8%–50.3%) but higher rates of FG1–2 papillary (11.1%–23.9%) and chromophobe histologic subtypes (6.2%–8.5%). Overall, 14.5% individuals harbored FG3–4 clear cell (9.8%) or FG3–4 papillary histologic subtypes (4.8%), and both were more prevalent in men. FG3–4 clear-cell and FG3–4 papillary histologic subtypes increased with age, more so in women than in men. The overall rate of synchronous metastases was 0.4% and ranged from 0 in the multilocular cystic subtype to 0.9% in the FG3–4 papillary histologic subtype, respectively, except for 13.8% in the sarcomatoid dedifferentiation histologic subtype. Conclusions: Most T1a 0- to 2-cm renal cell carcinoma represents the low-grade clear-cell or low-grade papillary histologic subtype, with an FG3–4 minority. Even in patients with the FG3–4 histologic subtype, rates of synchronous metastases are virtually zero.

The individual clinical significance of a positive surgical margin (PSM) after radical prostatectomy has remained controversial. Studies have suggested that the Gleason grade (GG) at the PSM could improve predictive accuracy and decision making. Our objective was to systematically review the reported data to determine the effect of the GG at the PSM on the prognosis after radical prostatectomy. A systematic review was conducted by searching MEDLINE/PubMed for studies reported by June 2019 in accordance with the Preferred Reporting Items for Systematic Review statement. The keywords used included prostate cancer, radical prostatectomy, positive surgical margin, Gleason score, and/or Gleason grade. After a systematic literature review, 10 studies were included, comprising 14,108 patients, of whom 2454 (17.4%) had a PSM and 428 (14%) eventually experienced biochemical recurrence (BCR) within a median follow-up of 18 to 156 months. Data on neoadjuvant or adjuvant therapy were not estimable. In a meta-analysis, GG4 at PSM was significantly associated with BCR compared with GG3 (pooled hazard ratio, 1.87; 95% confidence interval, 1.53-2.28; z = 6.16). The Cochrane Q test (χ2 = 5.88; P = .318) and I2 test (I2 = 15.0%) showed that no significant heterogeneity was present. GG4 at a PSM is a feature of biologically and clinically aggressive prostate cancer that is associated with a significant increase risk of BCR. GG at PSM should be recorded in each pathological report. Given this adverse prognostic value patients with GG4 at the PSM should be considered for multimodal therapy such as radiotherapy.

Objective: To investigate the oncologic safety of neurovascular bundles (NVB) preservation at radical prostatectomy (RP) in patients with high-risk and/or locally advanced prostate cancer (PCa). Material and methods: Within a two-institutional high-volume center database we identified patients who harbored high-risk PCa at RP (2000–2017). Only patients with D’Amico high-risk PCa were included. Kaplan–Meier and multivariable Cox regression models tested the effect of NVB preservation on biochemical recurrence (BCR), metastasis and overall survival (OS). Subgroup analyses focused on patients with clinical stage T3 and/or biopsy ISUP grade 5 and pathologic stage T3. Results: Of 4351 patients with D’Amico high-risk, 35.7% vs. 38.0% vs. 26.3% underwent bilateral vs. unilateral vs. no NVB preservation, respectively. At 120 months after RP BCR-free, metastasis-free survival and OS rates were 62.2% vs. 44.3% vs. 27.1% (p < 0.001), 83.7% vs. 66.7% vs. 60.3% (p < 0.001), and 91.8% vs. 87.5% vs. 72.3% (p < 0.001) for bilateral vs. unilateral vs. no NVB preservation, respectively. In multivariable Cox regression models, bilateral and unilateral compared to no NVB preservation did not increase the risk for BCR, metastasis or death in the entire cohort and in subgroups with clinical stage T3 and/or biopsy ISUP grade 5, as well as pathologic stage T3. Conclusions: NVB preservation was not associated with worse oncological outcome in patients with high-risk and/or locally advanced PCa and may be offered to well-selected patients who are at risk of harboring nonorgan-confined PCa.

The purpose of this study was to assess the prognostic value of hemoglobin (Hb) in patients with metastatic hormone-sensitive prostate cancer (HSPC). The PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched in December 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared patients with HSPC with normal and low Hb levels to determine their ability to predict overall survival, cancer-specific survival, progression-free survival, and castration-resistant prostate cancer-free survival. Formal meta-analyses were performed for these outcomes. The systematic review identified 25 studies including 6614 patients; 21 studies comprising 5782 patients were eligible for meta-analysis. Low Hb levels were associated with worse overall survival (pooled hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.15-1.29), cancer-specific survival (pooled HR, 1.46; 95% CI, 1.24-1.72), progression-free survival (pooled HR, 1.21; 95% CI, 1.14-1.28), and castration-resistant prostate cancer-free survival (pooled HR, 1.37; 95% CI: 1.18-1.57). Subgroup analyses revealed that low Hb levels were also associated with poor overall survival in patients with both “high-volume” (pooled HR, 1.49; 95% CI, 1.29-1.72) and “low-volume” HSPC (pooled HR, 1.40; 95% CI, 1.13-1.73). This meta-analysis revealed that low Hb serum levels in patients with metastatic HSPC were associated with increased risks of overall mortality, cancer-specific mortality, disease progression, and biochemical recurrence. Furthermore, Hb levels were independently associated with overall survival in the “high-volume” and “low-volume” HSPC subgroups. Therefore, it might be useful to incorporate Hb testing into prognostic tools for metastatic HSPC.

Background Lymph node invasion (LNI) at nephrectomy is one of the most important predictors of mortality in patients with nonmetastatic renal cell carcinoma (RCC). We analyzed the effect of histology on lymph node metastases at nephrectomy and its effect on survival in a contemporary cohort of patients with nonmetastatic RCC. Methods Within the Surveillance, Epidemiology, and End Results database (2004-2015), we identified 100,060 patients with clear-cell, papillary, chromophobe, sarcomatoid, and collecting duct RCC, who underwent nephrectomy with or without lymph node dissection for nonmetastatic RCC. Logistic regression models, cumulative incidence plots, and competing-risks regression models were performed. Results Overall, 10,590 patients underwent lymph node dissection for nonmetastatic RCC. Of these, LNI was recorded in 52 (7.0%), 615 (8.7%), 282 (13.9%), 316 (25.1%), 129 (38.3%), 45 (71.4%) patients with chromophobe, clear-cell, nonotherwise specified RCC, papillary, sarcomatoid, and collecting duct RCC histological subtypes, respectively. In logistic regression models, relative to clear-cell, papillary Odds ratio (OR 3.9), sarcomatoid (OR 6.3), collecting duct (OR 14.6) but not chromophobe RCC (OR 0.9; P = 0.5) independently predicted LNI at surgery. Moreover, in competing-risks regression models, LNI increased the risk of CSM 1.8-fold for sarcomatoid, 3.6-fold for clear-cell, 4.1-fold for papillary, and 6.7-fold for chromophobe histological subtype. Conclusions Histology is an independent predictor of increased risk of LNI at nephrectomy. Moreover, the effect of pathological nodal stage on survival differs according to different histology.

Objectives: To test the effect of stage and grade migration on cancer specific mortality (CSM) in renal cell carcinoma (RCC) patients, according to clear cell (ccRCC) vs. non-ccRCC histology. Methods and Materials: Within the Surveillance, Epidemiology, and End Results registry (2004–2015), we identified patients with ccRCC and non-ccRCC (papillary [papRCC], chromophobe [chRCC], sarcomatoid [sarcRCC], and collecting duct [cdRCC]). Two consecutive time groups were considered – historical (2004–2009) and contemporary era (2010–2015). Temporal trends of tumor characteristics were evaluated. Cumulative incidence plots and multivariable competing risks regression models tested the effect of year groups on CSM. Results: Overall, 24,746 and 73,228 patients with non-ccRCC and ccRCC were evaluated. Of those, 42% and 58% were recorded in historical and contemporary era. Time trend analyses showed (1) tumor size decreased for non-ccRCC (estimated annual percent changes [EAPC]: −1.1%; P

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

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

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

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

AimsTo compare the 1973 WHO and the 2004/2016 WHO grading systems in patients with urothelial carcinoma of urinary bladder (UCUB), since no consensus has been made which classification should supersede the other and since both are recommended in clinical practice.MethodsNewly diagnosed patients with Ta UCUB treated with transurethral resection of bladder tumour were abstracted from the Surveillance, Epidemiology and End Results database (2010–2016). Kaplan-Meier plots and multivariable Cox regression models (CRMs) tested cancer-specific mortality (CSM), according to 1973 WHO (G1 vs G2 vs G3) and to 2004/2016 WHO (low-grade vs high-grade) grading systems.ResultsOf 35 986 patients, according to 1973 WHO grading system, 8165 (22.7%) were G1, 17 136 (47.6%) were G2 and 10 685 (29.7%) were G3. According to 2004/2016 WHO grading system, 24 961 (69.4%) were low-grade versus 11 025 (30.6%) high-grade. In multivariable CRMs, G3 (HR: 2.05, pConclusionsFrom a statistical standpoint, it appears that the 2004/2016 WHO grading system holds a small, although measurable advantage over the 1973 WHO grading system. Other considerations, such as intraobserver and interobserver variability may represent an additional matric to consider in deciding which grading system is better.

Historical data demonstrated similar survival outcomes in patients with stage I nonseminoma germ-cell tumor of the testis (NSGCTT) subjected to either surveillance or active treatment (AT) after orchiectomy. However, data with long-term follow-up are unavailable. We tested contemporary treatment rates and their effect on cancer-specific mortality (CSM) and other-cause mortality (OCM) relative to surveillance, as well as after stratification between chemotherapy (CHT) versus retroperitoneal lymph node dissection (RPLND).We identified patients with stage I NSGCTT with initial orchiectomy within the Surveillance, Epidemiology, and End Results (SEER) database (1988-2015). Subsequent surveillance versus CHT versus RPLND use rates were reported. Cumulative incidence plots and multivariable competing-risks regression (CRR) models were used after propensity score (PS) matching. These tests first compared surveillance versus AT (CHT vs. RPLND) and subsequently CHT versus RPLND.Of 5034 patients with stage I NSGCTT, 61.2%, 24.9%, and 13.9%, respectively, underwent surveillance, CHT, and RPLND. Between 1988 and 2015, surveillance (estimated annual percentage change [EAPC]: +1.1%, P .001) and CHT (EAPC: +2.3%, P .001) rates increased. RPLND rates decreased (EAPC: -5.7%; P .001). After PS matching, CRR models failed to identify AT as an independent predictor of lower mortality relative to surveillance. However, after PS matching, CRR models identified RPLND as an independent predictor of lower CSM (hazard ratio, 0.26; P = .002) relative to CHT. No difference in OCM rates was recorded (hazard ratio, 1.25; P = .2).Surveillance and CHT use rates increased while RPLND decreased in the last two decades. Virtually the same outcomes were recorded between surveillance and AT. However, within AT, RPLND was associated with lower CSM than CHT.

Purpose:Cryoablation is done in select patients with pT1b nonmetastatic renal cell carcinoma without convincing proof of efficacy. Our aim was to test for differences in the cancer specific mortality rate for cryoablation and partial nephrectomy in T1b nonmetastatic renal cell carcinoma cases.Materials and Methods:In the 2004 to 2015 SEER (Surveillance, Epidemiology, and End Results) database we identified 5,763 patients with a T1b tumor treated with cryoablation or partial nephrectomy. Modeling relied on multivariable logistic regression models predicting cryoablation vs partial nephrectomy. After 1:2 ratio propensity score matching between patients treated with cryoablation vs partial nephrectomy we used cumulative incidence plot and competing risks regression to test differences in cancer specific mortality and other cause mortality rates.Results:Relative to the 5,521 patients who underwent partial nephrectomy the 242 treated with cryoablation were older, had smaller tumors and more frequently harbored unclassified renal cell carcinoma of low or unknown grade. Median followup was 38 months. In multivariable logistic regression models predicting cryoablation vs partial nephrectomy more advanced patient age was an independent predictor (OR 1.03; p=0.007). After propensity score matching and other cause mortality adjustment the 5-year cancer specific mortality rate was 2.5-fold higher after cryoablation than after partial nephrectomy (p=0.03). Conversely after propensity score matching and cancer specific mortality adjustment the 5-year other cause mortality rate was similar to that of partial nephrectomy after cryoablation (HR 1.45, p=0.12). The major limitation of this study was the lack of recurrence and metastatic progression data.Conclusions:The current findings demonstrated a 2.5-fold increase in cancer specific mortality when cryoablation was performed in patients with pT1b renal cell carcinoma. This observation should be interpreted as a contraindication to cryoablation outside clinical trials or institutional protocols.

Background: Use of inpatient palliative care (IPC) in the treatment of advanced cancer represents a well-established guideline recommendation. A recent analysis showed that patients with genitourinary cancer benefit from IPC at the second lowest rate among 4 examined primary cancers, namely lung, breast, colorectal, and genitourinary. Based on this observation, temporal trends and predictors of IPC use were examined in patients with metastatic urothelial carcinoma of the bladder (mUCB) receiving critical care therapies (CCTs). Patients and Methods: Patients with mUCB receiving CCTs were identified within the Nationwide Inpatient Sample database (2004–2015). IPC use rates were evaluated in estimated annual percentage change (EAPC) analyses. Multivariable logistic regression models with adjustment for clustering at the hospital level were used. Results: Of 1,944 patients with mUCB receiving CCTs, 191 (9.8%) received IPC. From 2004 through 2015, IPC use increased from 0.7% to 25.0%, respectively (EAPC, +23.9%; PPPP=.02) were associated with higher IPC rates. Conversely, Hispanic race (OR, 0.42; P=.03) and being hospitalized in the Northeast (OR, 0.36; P=.01) were associated with lower rate of IPC adoption. Finally, patients with a primary admission diagnosis that consisted of infection (OR, 2.05; P=.002), cardiovascular disorders (OR, 2.10; P=.03), or pulmonary disorders (OR, 2.81; P=.005) were more likely to receive IPC. Conclusions: The rate of IPC use in patients with mUCB receiving CCTs sharply increased between 2004 and 2015. The presence of liver metastases, infections, or cardiopulmonary disorders as admission diagnoses represented independent predictors of higher IPC use. Conversely, Hispanic race, nonteaching hospital status, and hospitalization in the Midwest were identified as independent predictors of lower IPC use and represent targets for efforts to improve IPC delivery in patients with mUCB receiving CCT.

Background: Marital status rates may have changed over time in prostate cancer (PC) patients and may have affected cancer-specific mortality (CSM) and other-cause mortality (OCM). Methods: Within the Surveillance, Epidemiology, and End Results database (2004–2015), we identified PC patients who were either married (n = 326,664) or unmarried (n = 106,533). Temporal trends, cumulative incidence plots, as well as multivariable competing risks regression analyses focused on (1) the overall population, (2) D'Amico low-risk N0M0 PC, (3) D'Amico intermediate-risk N0M0 PC, (4) D'Amico high-risk N0M0 PC, (5) N1M0 PC, and (6) M1 PC patients. Results: Of all, 24.6 % were unmarried and increased trend over time (23.0%–26.9%, P < 0.001). Unmarried men experienced higher CSM rates (9.8% vs. 6.3% in married men, P < 0.001) and OCM rates (24.3% vs. 17.1% in married men, P < 0.001) in the overall population, as well as in all subgroup analyses. Unmarried status represented an independent predictor of higher CSM (hazard ratio: 1.19, P < 0.001) and OCM (hazard ratio: 1.41, P < 0.001) in the overall cohort, as well as in all subgroup analyses except for the N1M0 subgroup, where marital status did not reach independent predictor status for CSM. Conclusions: Unmarried PC patients are at higher risk of CSM and OCM. This relationship applies to all stage subgroups, except for the N1M0 subgroup. Consequently, unmarried individuals should ideally benefit of improved counseling, closer follow-up, as well as of other measures aimed at reducing the CSM and OCM disadvantages.

Background: We examined the changes over time in other-cause mortality (OCM) rates in patients with clinically localized prostate cancer (PCa) as an indicator of patient selection. Patients and Methods: Within the Surveillance, Epidemiology, and End Results database (1987-2011), we identified patients with PCa treated with either radical prostatectomy (RP) (n = 230,969; 62.8%) or external beam radiation therapy (EBRT) (n = 136,915; 37.2%). Temporal trends and multivariable Cox regression analyses assessed OCM at 5 years using stratification according to year of diagnosis (1987-1991 vs. 1992-1996 vs. 1997-2001 vs. 2002-2006 vs. 2007-2011), age group, and ethnicity. Results: In patients who had undergone RP, the OCM rates at 5 years of follow-up decreased over time from 7.9% to 2.4% (slope, −0.25%/year) versus from 15.2% to 9.9% after EBRT (slope, −0.29%/year). The greatest decrease in 5-year OCM rates over time was recorded in patients ≥ 75 years (16.0%-12.0%; slope, −0.25%/year), followed by younger age categories (70-74 years, −0.21%/year; 65-69 years, −0.17%/year; 60-64 years, −0.10%/year; < 60 years, −0.07%/year), as well as in African-American men (11.0%-5.1%; slope, −0.32%/year), followed by Caucasian (7.6%-3.4%; slope, −0.21%/year) and Hispanic men (7.0%-3.1%; slope, −0.20%/year; all P

Background: The incidence of pT0 prostate cancer (CaP) at radical prostatectomy (RP) is extremely rare. We performed the first population-based analysis of pT0 CaP at RP. Methods: Within the Surveillance, Epidemiology, and End Results database (2004–2015), we tested for clinical and pathological characteristics according to pT0 vs. non-pT0 CaP and included a multivariable logistic regression model. Results: pT0 was identified in 358 (0.2%) out of 160,532 clinically localized RP patients. The majority of pT0 patients presented with initial prostate-specific antigen (PSA)

Purpose: There is no contemporary proof of cancer-control benefits in octogenarian clinically localized prostate cancer (PCa) patients with life expectancy (LE) < 10years. Therefore, cancer-specific mortality (CSM) rates after external beam radiation therapy (EBRT) vs. no local treatment (NLT) were tested in octogenarian PCa patients with LE < 10years. Methods: Within the surveillance, epidemiology, and end results database (2004–2015), we identified 22,361 octogenarian clinically localized PCa patients who either received EBRT or NLT. Temporal trends, cumulative incidence plots and multivariable competing-risks regression analyses (MCR) were used after propensity score matching. Sensitivity analyses were performed according to D’Amico risk groups and LE > 5years. Results: Of all, 7325 (32.8%) received EBRT vs. 15,036 (67.2%) received NLT. Rates of EBRT significantly increased over time (25.0–42.4%). Overall, 10-year CSM rates were 10.6% vs. 17.0% and 10-year other-cause mortality rates were 50.3% vs. 58.1%, in EBRT vs. NLT patients (both p < 0.001). In MCR focusing on the overall cohort, EBRT represented an independent predictor of lower CSM (hazard ratio: 0.5). In sensitivity analyses, hazard ratios of 0.5 (p < 0.001), 0.5 (p < 0.001) and 0.8 (p = 0.5) were, respectively, recorded in D’Amico high-, intermediate- and low-risk patients. In sensitivity analyses addressing patients with LE > 5years virtually the same results were recorded. Conclusions: In octogenarian patients with LE < 10years, EBRT seems to be associated with lower CSM in D’Amico high-risk, as well as in D’Amico intermediate-risk patients relative to their NLT counterparts. Based on these observations, greater consideration for EBRT may be given in octogenarian patients.

We tested the effect of marital status on cytoreductive nephrectomy, metastasectomy, and systemic therapy rates, as well as on cancer-specific mortality (CSM) in patients with metastatic clear cell renal carcinoma (mccRCC). Within the Surveillance, Epidemiology and End Results database (2004–2015), we identified 6975 patients (4806 men and 2169 women) with metastatic clear cell renal carcinoma. Temporal trend analyses, logistic regression models, cumulative incidence plots, and competing-risk regression models were used. Overall, 1450 men and 1018 women were unmarried (30.2% and 47.0%, respectively). In men, unmarried status was an independent predictor of lower cytoreductive nephrectomy rate (OR: 0.54), lower metastasectomy rate (OR: 0.70), and lower systemic therapy rate (OR: 0.70). Conversely, in women, unmarried status was an independent predictor of lower cytoreductive nephrectomy rate (OR: 0.63) and of lower systemic therapy rate (OR: 0.80), but not of lower metastasectomy rate (OR: 0.83; p = 0.12). In multivariable competing-risk regression analyses, unmarried status was an independent predictor of higher CSM in men (HR: 1.15), but not in women (HR 0.97, p = 0.6). Unmarried men are at higher risk of not benefiting of cytoreductive nephrectomy, metastasectomy, or systemic therapy than their married counterparts. Unmarried women are at higher risk of not benefiting of cytoreductive nephrectomy or systemic therapy. These gender-related differences cumulate in higher CSM in unmarried men, but not in unmarried women.

Aim: This study analyzed the effect of metastasectomy on overall mortality (OM) and perioperative outcomes in patients with metastatic renal cell carcinoma (mRCC) treated exclusively with targeted therapy. Materials and Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database (2006-2015), Kaplan–Meier analyses and multivariable Cox regression models tested for OM. Using the National Inpatient Sample (NIS) database (2006-2015), complication rates and in-hospital mortality were evaluated. Results: Within the SEER database, 437 (12.2%) out of 3,654 patients underwent metastasectomy. Metastasectomy was associated with lower OM risk (median survival 11 vs. 9 months, hazard ratio=0.83; p=0.002). Within the NIS database, 351 such patients were identified. Complications and in-hospital mortality were 55.0% and 4.6%, respectively. Conclusion: Metastasectomy in patients with mRCC treated exclusively with targeted therapy is associated with lower OM risk, however, based on short duration of expected survival. Complications and in-hospital mortality rates are not negligible.

Purpose: To analyze lymph node invasion (LNI) rates according to tumor characteristics and to test the impact of LNI and its extent on cancer specific mortality (CSM) in surgically-treated non metastatic urothelial upper urinary tract carcinoma (UTUC) patients. Materials and methods: Within the SEER database (2004–2014), we identified 2098 patients with histologically confirmed non-metastatic urothelial carcinoma of renal pelvis or ureter who underwent NU with LND. LNI rates stratified according to tumor location and stage were described. Kaplan-Meier plots illustrated CSM rates according to LNI and its extent. Multivariable Cox regression models (MCRMs) tested the effect of LNI and its extent on CSM. Results: Of 2098 UTUC patients, who underwent nephroureterectomy with lymph node dissection, 646 (33%) had LNI. The median number of removed lymph nodes was 3 [Interquartile range (IQR): 1–7]. The median number of positive lymph nodes in patients, who harbored LNI was 1 (IQR:1–3). LNI rates according to tumor location were, respectively, 23.6% for ureteral and 36.5% for renal pelvis tumors. LNI rates according to tumor stage were 9.6, 18.0, 38.7 and 63.9%, for respectively, T1, T2, T3 and T4 UTUC. In MCRMs, LNI achieved independent predictor status for higher CSM (HR 3.00; p < 0.001). Finally, in MCRMs, number of positive lymph nodes defined as the 75th percentile (n ≥ 3) achieved independent predictor status for higher CSM (HR 1.37; p = 0.04). Conclusions: LNI in non-metastatic UTUC patients is the most important determinant of CSM. Number of positive lymph node is independently associated with higher CSM. In consequence, lymph node dissection can provide extensive prognostic information.

Background Analyzing the relationship between perioperative outcomes and age in urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC) in a continuous fashion may provide detailed information on the increased risk of complications in older patients, even after accounting for different comorbidity profiles. Given the limited data available in the literature, we tested these relationships within a large scale, population-based database. Materials and Methods Within the NIS database (2003–2015), we identified patients who underwent RC for UCB. Multivariable logistic regression (MLoR) and Poisson regression (MPR) models were used after adjustment for clustering and stratification for comorbidity profiles. Results Overall, 20,144 patients underwent RC with a median age of 70 years (interquartile range: 62–77). In MLoR models, continuously coded age represented an independent predictor of overall (odds ratio [OR]: 1.008, 95%-confidence interval [CI]: 1.005–1.012), cardiac (OR: 1.042, 95%-CI: 1.035–1.049), vascular (OR: 1.024, 95%-CI: 1.014–1.034), respiratory (OR: 1.016, 95%-CI 1.009–1.022), miscellaneous medical (OR: 1.013, 95%-CI: 1.009–1.017), infectious (OR: 1.012, 95%-CI 1.004–1.019), transfusions (OR: 1.011, 95%-CI 1.007–1.015) and bowel obstruction (OR: 1.009, 95%-CI 1.004–1.013) complications, and in-hospital mortality (OR: 1.057, 95%-CI 1.039–1.075). Conversely, patients age did not predict intraoperative (p = 0.7), genitourinary (p = 0.9), operative wound (p = 0.2) and miscellaneous surgical complications (p = 0.1). In MPR models, patients age predicted longer LOS (relative risk [RR]: 1.002, 95%-CI 1.001–1.003). Finally, a decreasing effect of age was observed in patients low vs high comorbidity burden for cardiac, respiratory and overall complications. Conclusions Most of early postoperative RC complications are related to patients age, but its impact varies according to comorbidity profile. Further studies are needed to validate our findings that may be then considered for individual counselling and informed consent, as well as for health expenditure planning.

Background: The role of robot assistance is increasingly gaining importance among all major surgical uro-oncological procedures (MSUPs). However, contemporary analyses showed that total hospital charges (THCGs) related to robot-assisted procedures exceed those of open procedures. Based on increasing familiarity with robot-assisted surgery, we postulated that THCGs may have decreased over the past half-decade. Thus, we tested contemporary trends and THCGs related to robot-assisted vs nonrobot-assisted MSUPs. Materials and Methods: Within the National Inpatient Sample database (2009-2015), we identified patients who underwent robot-assisted vs nonrobot-assisted (open or laparoscopic) MSUPs, which included radical prostatectomy (RP), radical nephrectomy (RN), partial nephrectomy (PN), and radical cystectomy (RC). Rates of robot-assisted MSUPs were evaluated using estimated annual percentage changes (EAPCs) analyses. The t-test was used to examine statistically significant differences between mean THCGs according to either robot-assisted or nonrobot-assisted approach. Finally, linear regression analyses were tested for annual variation in the mean THCGs. Results: Of 128,367 MSUPs, 47.7% were robot-assisted. Overall, robot-assisted surgery rates among MSUPs increased from 40.3% to 57.6% (EAPC: +6.3%, p < 0.001) between 2009 and 2015. The mean THCGs for robot-assisted RP, RN, PN, and RC were $13,799, $18,789, $16,574, and $33,575, respectively. The observed mean THCGs differences between robot-assisted and nonrobot-assisted MSUPs were +$1594, +$1592, and +$1829 for RP, RN, and RC, respectively (all p < 0.05). Conversely, no statistically significant difference in the mean THCGs was reported between robot-assisted and nonrobot-assisted PN (+$367, p > 0.05). Finally, the annual observed mean THCGs linearly decreased for all robot-assisted MSUPs during the study period. Conclusions: Rates of robot-assisted MSUPs exponentially increased between 2009 and 2015. Although the mean THCGs decreased in a significant manner during the study period for all MSUPs, THCGs of robot-assisted RP, RN, and RC still exceed those of their respective nonrobot-assisted counterparts. Conversely, no differences in the mean THCGs were reported between robot-assisted vs nonrobot-assisted PN.

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

Background: Serum cholinesterase (ChE) a serine hydrolase that catalyses the hydrolysis of esters of choline, is involved in cellular proliferation and differentiation, therefore affecting carcinogenesis. The aim of this study was to understand the prognostic role of preoperative serum ChE in patients with radiation-recurrent prostate cancer (CaP) treated with salvage radical prostatectomy (SRP). Material and methods: This retrospective study included 214 patients with radiation-recurrent CaP treated with SRP from January 2007 to December 2015 at 5 academic centers. Patients were considered with abnormal/decreased ChE levels if

Background: We hypothesized that lymph node dissection (LND) at salvage radical prostatectomy may be associated with lower cancer-specific mortality (CSM) and we tested this hypothesis. Methods: We relied on surveillance, epidemiology, and end results (2004–2016) to identify all salvage radical prostatectomy patients. Categorical, as well as univariate and multivariate Cox regression models tested the effect of LND (LND performed vs. not), as well as at its extent (log-transformed lymph node count) on CSM. Results: Of 427 salvage radical prostatectomy patients, 120 (28.1%) underwent LND with a median lymph node count of 6 (interquartile range [IQR], 3–11). According to LND status, no significant or clinically meaningful differences were recorded in PSA at diagnosis, stage and biopsy Gleason score at diagnosis, except for age at prostate cancer diagnosis (LND performed 63 vs. 68 years LND not performed, p

Background We compared upgrading and upstaging rates in low risk and favorable intermediate risk prostate cancer (CaP) patients according to racial and/or ethnic group: Mexican-Americans and Caucasians. Methods Within Surveillance, Epidemiology and End Results database (2010–2015), we identified low risk and favorable intermediate risk CaP patients according to National Comprehensive Cancer Network guidelines. Descriptives and logistic regression models were used. Furthermore, a subgroup analysis was performed to test the association between Mexican-American vs. Caucasian racial and/or ethnic groups and upgrading either to Gleason-Grade Group (GGG II) or to GGG III, IV or V, in low risk or favorable intermediate risk CaP patients, respectively. Results We identified 673 (2.6%) Mexican-American and 24,959 (97.4%) Caucasian CaP patients. Of those, 14,789 were low risk (434 [2.9%] Mexican-Americans vs. 14,355 [97.1%] Caucasians) and 10,834 were favorable intermediate risk (239 [2.2%] Mexican-Americans vs. 10,604 [97.8%] Caucasians). In low risk CaP patients, Mexican-American vs. Caucasian racial and/or ethnic group did not result in either upgrading or upstaging differences. However, in favorable intermediate risk CaP patients, upgrading rate was higher in Mexican-Americans than in Caucasians (31.4 vs. 25.5%, OR 1.33, P = 0.044), but no difference was recorded for upstaging. When comparisons focused on upgrading to GGG III, IV or V, higher rate was recorded in Mexican-American relative to Caucasian favorable intermediate risk CaP patients (20.4 vs. 15.4%, OR 1.41, P = 0.034). Conclusion Low risk Mexican-American CaP patients do not differ from low risk Caucasian CaP patients. However, favorable intermediate risk Mexican-American CaP patients exhibit higher rates of upgrading than their Caucasian counterparts. This information should be considered at treatment decision making.

Purpose: Unmarried status is an established risk factor for worse cancer control outcomes in various malignancies. Moreover, several investigators observed worse outcomes in unmarried males, but not in females. This concept has not been tested in upper tract urothelial carcinoma and represents the topic of the study. Methods: Within Surveillance, Epidemiology and End Results database (2004–2016), we identified 8833 non-metastatic upper tract urothelial carcinoma patients treated with radical nephroureterectomy (5208 males vs. 3625 females). Kaplan Meier plots and multivariable Cox regression models predicting overall mortality, other-cause mortality and cancer-specific mortality were used. Results: Overall, 1323 males (25.4%) and 1986 females (54.8%) were unmarried. Except for lower rates of chemotherapy in unmarried males (15.6 vs. 19.6%, P = 0.001) and unmarried females (13.8 vs. 23.6%, P < 0.001), no clinically meaningful differences were recorded between males and females. In multivariable Cox regression models, unmarried status was an independent predictor of higher overall mortality in both males (Hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.19–1.48, P < 0.001) and females (HR: 1.13, 95%CI: 1.00–1.27, P = 0.04), as well as of higher other-cause mortality in both males (HR: 1.53, 95%CI: 1.26–1.84,P < 0.001) and females (HR: 1.43, 95%CI: 1.15–1.78,P < 0.01). However, higher cancer-specific mortality was only recorded in unmarried males (HR: 1.24, 95%CI: 1.08–1.42, P < 0.01), but not in females (HR: 1.02, 95%CI: 0.89–1.17, P = 0.7). Conclusion: Unmarried status is a marker of worse survival in both males and females and should be flagged as an important risk factor at diagnosis, in both sexes. In consequence, unmarried patients represent candidate for interventions aimed at decreasing the survival gap relative to married counterparts.

The indications for adjuvant vascular endothelial growth factor–tyrosine kinase inhibitor (VEGF-TKI) agents after curative intent nephrectomy for renal cell carcinoma are still a matter of debate. The ASSURE, PROTECT and ATLAS trials have failed to meet their primary end-points. Conversely, S-TRAC has shown a disease free survival (DFS) benefit. To date, meta-analyses have repeatedly proved the absence of a clinical benefit, in term of DFS and overall survival (OS). Nevertheless, the results of the SORCE trial have been recently released and might add valuable information. We pooled the results of all five reported trials testing for any potential DFS and OS benefits associated with VEGF-TKI use. Interestingly, for pooled DFS we found a marginal positive hazard ratio (HR) of 0.92 (95% confidence interval [CI] 0.85-1.00; P-value = 0.049) in favor of adjuvant VEGF-TKI agents. This benefit was more pronounced for DFS in the sub-groups of only high-risk patients (HR: 0.89, 95% CI 0.80-0.99; P-value = 0.026), but less pronounced in clear-cell only subgroup (HR 0.92, 95% CI: 0.85-1.00; P-value = 0.044). Overall survival benefit was instead not reached. However, pooled relative risk for high-grade (grade ≥3 according to CTCAE classification) adverse events was irremediably high, 2.56 (95% CI: 2.15-3.04; P-value < 0.001). Given the marginal benefit in terms of DFS and the drawback of high-grade adverse events, even after the SORCE trial publication, adjuvant VEGF-TKIs therapy cannot be considered in the whole group of patients with non-metastatic high-risk renal cell carcinoma after surgery.

Purpose To test the effect of sex on histologic subtype, stage at presentation, treatment, and cancer-specific mortality (CSM) in urethral cancer. Patients and Methods We identified urethral cancer patients within the Surveillance, Epidemiology, and End Results (SEER) registry (2004-2016). After matching for tumor and patient characteristics, cumulative incidence plots and multivariable competing risks regression models, adjusted for other-cause mortality, tested CSM according to sex. Results Of 1645 eligible urethral cancer patients, 1073 (65%) were male. Urothelial histologic subtype was most frequent in male (59%) but not female (27%) subjects. Adenocarcinoma, squamous cell carcinoma, and other histologies were more frequent in female patients. Most male subjects harbored T1N0M0 (32%) stage disease, whereas most female subjects harbored T3-4N0M0 (29%) stage disease. In urothelial and adenocarcinoma histologic subtypes, African American female subjects were most prevalent (31 and 78%) versus whites (16 and 52%) versus Hispanics (27 and 74%). In T1N0M0 stage, single-mode surgical treatment was more frequent in male than female patients (respectively, 73% vs 59%). In T3-4 and/or N1-2 stage disease, multimodal therapy was more frequent in female than male (42% vs 37%) patients. In nonmetastatic urethral cancer (T1-4N0-2M0), after propensity score matching for stage, race, treatment, and age, cumulative incidence plots showed 5-year CSM of 36% and 25% in female and male patients, respectively, and after further multivariable adjustment resulted in 1.3-fold higher CSM in female as opposed to male patients (P = .07). Conclusion Female patients with urethral cancer present with higher disease stage. Despite higher rates of multimodal therapy, and despite matching for stage disadvantage, female subjects with urethral cancer exhibited higher CSM.

Background We hypothesized that the residency status (rural area [RA] vs urban clusters [UC] vs urban areas [UA]) affects stage and cancer-specific mortality (CSM) in contemporary newly diagnosed prostate cancer (PCa) patients of all stages, regardless of treatment. Methods Newly diagnosed PCa patients with available residency status were abstracted from the Surveillance, Epidemiology, and End Results database (2004–2016). Propensity-score (PS) matching, cumulative incidence plots, multivariate competing-risks regression (CRR) models were used. Results Of 531,468 PCa patients of all stages, 6653 (1.3%) resided in RA, 50,932 (9.6%) in UC and 473,883 (89.2%) in UA. No statistically significant or clinically meaningful differences in stage at presentation or CSM were recorded. Conversely, 10-year other cause-mortality (OCM) rates were 27.2% vs 23.7% vs 18.9% (p p p Conclusion RA, and to a lesser extent UC, PCa patients are at higher risk of OCM than UA patients. Higher OCM may indicate shorter life expectancy and should be considered in treatment decision making.

Introduction: This manuscript aims to give an overview of current diagnostic, staging, and prognostic markers for prostate cancer (PCa) and discuss emerging approaches. The widespread use of PSA for early detection led to improved survival but at the cost of over-diagnosis, often associated with over-treatment and its adverse events. There is thus an unmet need for new markers to sustainably improve the diagnosis and risk assessment, thereby providing a more accurate treatment decision for each individual patient. Areas covered: Promising new molecular serum (PSA, PHI, 4Kscore®), urine (Progensa®, SelectMDx®, MiPS) and tissue-based markers (Ki-67, Prolaris®, ConfirmMDx®, Oncotype Dx®, Decipher®, Promark®) will be discussed in this review. Expert opinion: Over-diagnosis and difficulties in prognosticating clinical outcome among patients with similar histological and clinical parameters often lead to over- or under-treatment. New markers will probably be used with clinical and histopathological features as well as imaging diagnostics to capture the comprehensive biology and clinical behavior of PCa. New biomarkers open the avenue to avoid mpMRI with targeted biopsy in the future, thereby sparing risks and pitfalls associated with this approach. Before this utopia becomes reality, the panel of technologically complementary markers need to prove that they are better, cheaper, and faster than current strategies.

Objectives: To test contemporary rates and predictors of open conversion at minimally invasive partial nephrectomy (MIPN: laparoscopic or robotic partial nephrectomy). Materials and methods: Within the National Inpatient Sample database (2008–2015) we identified all MIPN patients and patients that underwent open conversion at MIPN. First, estimated annual percentage changes (EAPC) tested temporal trends of open conversion. Second, univariable and multivariable logistic regression models predicted open conversion at MIPN. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics. Results: Of 7649 MIPN patients, 287 (3.8%) underwent open conversion. The rates of open conversion decreased over time (from 12 to 2.4%; EAPC: 24.8%; p = 0.004). In multivariable logistic regression models predicting open conversion, patient obesity achieved independent predictor status (OR:1.80; p < 0.001). Moreover, compared to high volume hospitals, medium volume (OR:1.48; p = 0.02) and low volume hospitals (OR:2.11; p < 0.001) were associated with higher rates of open conversion. Last but not least, when the effect of obesity was tested according to hospital volume, the rates of open conversion ranged from 2.2 (non obese patients treated at high volume hospitals) to 9.8% (obese patients treated at low volume hospitals). Conclusion: Overall contemporary (2008–2015) rate of open conversion at MIPN was 3.8% and it was strongly associated with patient obesity and hospital surgical volume. In consequence, these two parameters should be taken into account during preoperative patients counselling, as well as in clinical and administrative decision making.