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Introduction: The nonmuscle invasive bladder cancer treated with BCG instillations in patients who smoke could potentially lead to poorer oncological results in the light of the new EAU risk groups classification for NMIBC that did not include BCG treated patients or smoking status., Patient and Methods: Outcomes from 1313 patients with nonmuscle invasive bladder cancer treated with TURBT, re-TURBT and BCG instillations at 13 academic hospital centers, since 2002, has been included in this retrospective study. The study variables, including cumulative smoking exposure have been analyzed. A multivariable Cox proportional hazard model was used to assess associations between smoking variables and disease progression and repeated in the EAU high risk and very high-risk group. The statistical significance threshold was set at 0.05, and the statistical analysis was performed using Stata/SE version 17 (StataCorp, College Station, TX, USA)., Results: Cox regression analysis revealed in 1313 patients diagnosed with T1G3 NMIBC that patients with a history of heavy and long-term smoking faced a more than twofold increased risk of disease progression compared to nonsmoker patients (HR 2.35; 95% CI: 1.7-3.2; P < 0.01) and a significantly poorer PFS for patients with a history of heavy long-term smoke exposure (P < 0.01). Patients with heavy long-term smoking exposure according to the EAU21 high-risk group had a PFS comparable to very high-risk patients and high-risk patients with heavy long-term smoking exposure showed a higher risk of progression when compared to the high-risk group (HR 1.4; 95% CI: 1.3-1.6; P < 0.01)., Conclusions: This study adds valuable information on the relationship between smoking and the progression of NMIBC and BCG therapy. The findings emphasize the need for healthcare providers to consider a patient's smoking history when managing NMIBC and express the need for individualized smoking cessation counseling and individualized treatment approach., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To test for specific anthropometric parameters to predict perioperative outcomes after thermal ablation (TA) for renal cell carcinoma (RCC)., Materials and Methods: Retrospective single center (2008-2022) analysis of 538 T1a-b RCC patients treated with TA. We tested for specific anthropometric parameters, namely skin to tumor distance (STTD), perirenal fat thickness (PFT), median psoas muscle axial area (PMAA) and median paravertebral muscle axial area (PVMAA), to predict TRIFECTA achievement: (1) absence of CLAVIEN-DINDO≥ 3 complications; (2) complete ablation; (3) absence of ≥ 30% decrease in eGFR. Univariable (ULRM) and multivariable logistic regression models (MLRM) were used for testing TRIFECTA achievement., Results: Overall, 103 patients (19%) did not achieve TRIFECTA. Of all anthropometric factors, only lower PMAA was associated with no TRIFECTA achievement (10 vs. 11 cm 2 , P = .02). However, ULRMs and MLRMs did not confirmed the aforementioned association. We than tested for the 3 specific TRIFECTA items. In separate ULRM and MLRM predicting incomplete ablation, both continuously coded STTD (Odds Ratio [OR]: 1.02; CI: 1.01-1.03; P = .02) and STTD strata (STTD > 10 cm; OR: 2.1; CI: 1.1-4.1; P = .03) achieved independent predictor status. Conversely, in separate ULRM and MLRM predicting CLAVIEN-DINDO ≥3 complications, both continuously coded PFT (OR: 1.04; CI: 1.01-1.07; P = .01) and PFT strata (PFT ≥ 14 mm; OR: 3.3; CI: 1.6-10.2; P = .003) achieved independent predictor status. Last, none of the anthropometric parameters were associated with eGFR decrease ≥ 30%., Conclusion: None of the tested anthropometric parameters predicted TRIFECTA achievement. However, when the 3 specific TRIFECTA items were tested, STTD and PFT were associated with, respectively, incomplete ablation and CLAVIEN-DINDO ≥ 3 complications., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Upper tract urothelial carcinoma is rare but has a poor prognosis. Prognostic factors have been extensively studied in order to provide the best possible management for patients. We have aimed to investigate commonly available factors predictive of recurrence and survival in this patient population at high risk of death and recurrence, with an emphasis on the effects of age (using a cutoff of 70 years) on survival outcomes., Patients and Methods: From 1387 patients with clinically nonmetastatic upper tract urothelial carcinoma treated with radical nephroureterectomy at 21 academic hospital centers between 2005 and 2021, 776 patients were eligible and included in the study. Univariable and multivariable Cox regression models were built to evaluate the independent prognosticators for intravesical and extravesical recurrence, overall survival, and cancer-specific survival according to age groups. A P value of <.05 was considered statistically significant., Results: We did not find an association between groups aged <70 and >70 years old and preoperatively clinical or histopathological characteristics. Kaplan-Meier analysis was found no statistical significance between the 2 age groups in terms of intravesical or extravesical recurrence (P = .09 and P = .57). Overall survival (P = .0001) and cancer-specific survival (P = .0001) have been found to be statistically significantly associated with age as independent predictors (confounding factors: gender, tumor size, tumor side, clinical T stage, localization, preoperative hydronephrosis, tumor localization, type of surgery, multifocality of the tumor, pathological grade, lymphovascular invasion, concomitant CIS, lymph node status, necrosis, or history of previous bladder cancer)., Conclusion: This research confirms that patients aged 70 and above who undergo radical nephroureterectomy may have worse outcomes compared to younger patients, older patients needing an improved care and management of UTUC to improve their outcomes in the setting of an increase in this aged population group., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: In patients affected by high-risk nonmuscle invasive bladder cancer (HR-NMIBC) progression to muscle invasive status is considered as the main indicator of local treatment failure. We aimed to investigate the effect of progression and time to progression on overall survival (OS) and to investigate their validity as surrogate endpoints., Methods: A total of 1,510 patients from 18 different institutions treated for T1 high grade NMIBC, followed by a secondary transurethral resection and BCG intravesical instillation. We relied on random survival forest (RSF) to rank covariates based on OS prediction. Cox's regression models were used to quantify the effect of covariates on mortality., Results: During a median follow-up of 49.0 months, 485 (32.1%) patients progressed to MIBC, while 163 (10.8%) patients died. The median time to progression was 82 (95%CI: 78.0-93.0) months. In RSF time-to-progression and age were the most predictive covariates of OS. The survival tree defined 5 groups of risk. In multivariable Cox's regression models accounting for progression status as time-dependent covariate, shorter time to progression (as continuous covariate) was associated with longer OS (HR: 9.0, 95%CI: 3.0-6.7; P < 0.001). Virtually same results after time to progression stratification (time to progression ≥10.5 months as reference)., Conclusion: Time to progression is the main predictor of OS in patients with high risk NMIBC treated with BCG and might be considered a coprimary endpoint. In addition, models including time to progression could be considered for patients' stratification in clinical practice and at the time of clinical trials design., Competing Interests: Declaration of competing interest Each of the authors certify that the manuscript represents original and valid work that has not been previously published and is not currently under consideration by any other journal. Additionally, all the authors: have given final approval of the submitted manuscript approved the contents of this paper and have participated sufficiently in the work to take public responsibility for all content. None of the contributing authors have any conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript. No funding or other financial support was received., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To determine risk categories for patients with prostate cancer (PCa) in active surveillance (AS) and to test the conditional survival (CS) that examined the effect of event-free survival since AS-entrance., Materials and Methods: From January 2012 to December 2020 we analyzed 606 patients with PCa enrolled in our AS program. Kaplan-Meier (KM) plots depicted AS-exit rate. Multivariable Cox regression models (MCRMs) tested for AS-exit rate independent predictors to determine risk categories. CS estimates were used to calculate overall AS-exit rate after event-free survival intervals of 1, 2, 3, and 5 years, and after stratification according to risk categories., Results: At MCRMs PSAd ≥ 0.15 (HR: 1.43; P-value 0.04), PI-RADS 4-5 (HR: 2.56; P-value <0.001) and number of biopsy positive cores ≥ 2 (HR: 1.75; P-value <0.001) were independent predictors of AS-exit. These variables were used to determine risk categories: low-, intermediate- and high-risk. Overall, according to CS-analyses, 5-year AS-exit free rate increased from 59.7% at baseline, to 67.3%, 74.7%, and 89.4% in patients who remained in AS respectively ≥1, ≥2, ≥3 and ≥5 years. After stratification according to risk categories, in those patients who remained in AS ≥ 5 years, 5-year AS-exit free rates increased from 76.3% to 100% in patients with a low-risk, from 62.7% to 83.7% in patients with an intermediate-risk and from 42.3% to 87.5% in patients with a high-risk., Conclusions: CS models showed a direct relationship between event-free survival duration and subsequent AS permanence in overall PCa patients and after stratification according to risk categories., Competing Interests: Declaration of Competing Interest Authors declare no conflicts of interest, including specific financial interests or relationships or affiliations relevant to the subject matter or materials discussed in the manuscript., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: To test TRIFECTA achievement [1) absence of CLAVIEN-DINDO ≥3 complications; 2) complete ablation; 3) absence of ≥30% decrease in eGFR] and local recurrence rates, according to tumor size, in patients treated with thermal ablation (TA: radiofrequency [RFA] and microwave ablation [MWA]) for small renal masses., Methods: Retrospective analysis (2008-2020) of 432 patients treated with TA (RFA: 162 vs. MWA: 270). Tumor size was evaluated as: 1) continuously coded variable (cm); 2) tumor size strata (0.1-2 vs. 2.1-3 vs. 3.1-4 vs. >4 cm). Multivariable logistic regression models and a minimum P-value approach were used for testing TRIFECTA achievement. Kaplan-Meier plots depicted local recurrence rates over time., Results: Overall, 162 (37.5%) vs. 140 (32.4%) vs. 82 (19.0%) vs. 48 (11.1%) patients harboured, respectively, 0.1 to 2 vs. 2.1 to 3 vs. 3.1 to 4 vs. >4 cm tumors. In multivariable logistic regression models, increasing tumor size was associated with higher rates of no TRIFECTA achievement (OR:1.11; P< 0.001). Using a minimum P-value approach, an optimal tumor size cut-off of 3.2 cm was identified (P< 0.001). In multivariable logistic regression models, 3.1 to 4 cm tumors (OR:1.27; P< 0.001) and >4 cm tumors (OR:1.49; P< 0.001), but not 2.1 to 3 cm tumors (OR:1.05; P= 0.3) were associated with higher rates of no TRIFECTA achievement, relative to 0.1 to 2 cm tumors. The same results were observed in separate analyses of RFA vs. MWA patients. After a median (IQR) follow-up time of 22 (12-44) months, 8 (4.9%), 8 (5.7%), 11 (13.4%), and 5 (10.4%) local recurrences were observed in tumors sized 0.1 to 2 vs. 2.1 to 3 vs. 3.1 to 4 vs. >4 cm, respectively (P= 0.01)., Conclusion: A tumor size cut-off value of ≤3 cm is associated with higher rates of TRIFECTA achievement and lower rates of local recurrence over time in patients treated with TA for small renal masses., Competing Interests: Conflicts of interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Seventy-five percent of bladder cancers are non-muscle invasive. The treatment strategy includes the transurethral resection of bladder tumor (TURB) followed by intravesical immunotherapy with the bacillus of Calmette-Guerin (BCG) or chemotherapy, depending on the grade of bladder tumor. Despite a proper BCG intravesical instillations schedule, up to 40% of patients present a failure within 2 years. The aim of this retrospective study was to investigate the predictive factors in the response to BCG in patients with a high-grade non-muscle invasive bladder cancer diagnosis., Materials and Methods: Patients with non-muscle invasive bladder cancer from 13 hospitals and academic institutions were identified and treated, from January 1, 2002, until December 31, 2012, with TURB and a subsequent re-TURB for restaging before receiving BCG. Follow-up was performed with urine cytology and cystoscopy every 3 months for 1 year and, successively every 6 months. Univariate and multivariate Cox regression models addressed the response to BCG therapy. Kaplan-Meier overall survival (OS) and cancer-specific survival (CSS) estimates were determined for BCG responsive vs. BCG unresponsive patients., Results: A total of 1,228 patients with non-muscle invasive bladder cancer were enrolled. Of 257 (20.9%) patients were BCG unresponsive. Independent predictive factors for response to BCG were: multifocality (HR: 1.4; 95% CI 1.05-1.86; P = 0.019), lymphovascular invasion (HR: 1.75; 95% CI 1.22-2.49; P = 0.002) and high-grade on re-TURB (HR: 1.39; 95% CI 1.02-1.91; P = 0.037). Overall survival was significantly reduced in BCG-unresponsive patients compared to BCG-responsive patients at 5 years (82.9% vs. 92.4%, P < 0.0001) and at 10 years (44.2% vs. 74.4%, P < 0.0001). Similarly, cancer-specific survival was reduced in BCG-unresponsive patients at 5 years (90.6% vs. 97.3%, P < 0.0001) and at 10 years (72.3% vs. 87.2%, P < 0.0001)., Conclusion: Multifocality, lymphovascular invasion, and high-grade on re-TURB were independent predictors for response to BCG treatment. BCG-unresponsive patients reported worse oncological outcomes., Competing Interests: Conflict of interests The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The aim of this multicenter study was to investigate the role of age (cut-off 70 years) at diagnosis in predicting oncologic behavior of pure carcinoma in situ of the bladder., Material and Methods: Inclusion criteria were: patients with pure CIS confirmed and that followed intravesical BCG treatment. Pure CIS was defined at any CIS not associated with another urothelial cancer. Exclusion criteria were: any CIS associated with invasive urothelial carcinoma. A total of 172 with pure CIS treated between January 1, 2002 and December 31, 2012 at 8 academic institutions met the inclusion criteria. The maintenance schedule was generally according to the EAU guidelines at the time RESULTS: A total of 99 (57.6%) patients had an age >70 years prior to TURBT. There was no difference between clinico-pathologic features among groups (group 1, age ≤ 70 years and group 2, age > 70 years), except that patients aged ≤ 70 years presented a larger size of CIS (35.6% vs. 21.2%), P = .02. In multivariable Cox regression analyses, the same clinico-pathologic factors (age, multifocality, and recurrent tumor state) were independently associated with worse RFS. Harrell's C-index was 65.75.In multivariable Cox regression analyses in addition to age (P = .006) and multifocality (P < .001) also BMI (P = .04) was independently associated with worse PFS. Harrell's C-index was 74.71 CONCLUSION: Advanced age at diagnosis appears to be associated with an increased risk of recurrence and progression of pure carcinoma in situ of the bladder. Elderly patients might fail to respond to BCG therapy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To investigate the use of apparent diffusion coefficient (ADC) values and other MRI features for predicting positive surgical margins (PSMs) in patients undergoing radical prostatectomy., Materials and Methods: We retrospectively identified 400 consecutive patients who underwent surgery for prostate cancer between January 2015 and June 2016. ADC values of the index lesion and other preoperative magnetic resonance imaging features, including tumor site, laterality, level, Prostate Imaging Reporting and Data System category, European Society of Urogenital Radiology extracapsular extension score, and prostate volume, were assessed. Univariate and multivariable logistic regression were performed. Performance in predicting the occurrence of PSMs was measured using the area under the curve (AUC). AUC differences were evaluated with the DeLong method. The Youden index was calculated to identify the ADC threshold to best discriminate patients with PSMs., Results: Of the 400 patients, 105 (26.2%) had PSMs after radical prostatectomy. ADC values, Prostate Imaging Reporting and Data System category, extracapsular extension score, tumor site, and laterality were significantly associated with PSMs (P < .001) in univariate analysis. The AUC of the predictive model based on ADC alone was 68.2% (95% confidence interval, 62.2-74.2%) and did not significantly differ from the best multivariable predictive model which combined laterality, and site with ADC to attain an AUC of 70.0% (95% confidence interval, 64.2-75.8%; DeLong P = .318). The ADC threshold that maximized the Youden index was 960.3 µm 2 /s., Conclusion: ADC values and preoperative magnetic resonance imaging features can help estimate the risk of PSMs after radical prostatectomy., Competing Interests: Disclosure Paul Summers declares a relationship with the following companies: QMRI Tech. The remaining authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To report long-term oncological outcomes after penile-sparing surgery (PSS) for superficial (Ta-Tis) or initially invasive (T1) penile cancer patients., Methods: We retrospectively analysed 85 patients with Ta/Tis/T1cN0cM0 penile cancer (1996-2018). All patients underwent PSS: circumcision, excision or laser ablation. First, Kaplan-Meier plots and multivariable Cox regression models tested tumor recurrence rates (any local/regional/metastatic). Second, Kaplan-Meier plots depicted progression-free survival (≥T2 or N1-3 or M1 disease)., Results: Median (IQR) follow-up time was 64 (48-95) months. Overall, 48 (56%) patients experienced tumor recurrence. Median (IQR) time to tumor recurrence was 34 (7-52) months. Higher recurrence rates were observed for Tis (65%) and T1 (64%), compared to Ta (40%), but these differences were not significant on multivariable Cox regression analyses (HR:2.0 with 95% CI [0.9-5.1] and HR:2.2 with 95% CI [0.9-5.9], respectively). Moreover, higher recurrence rates were observed for G2-3 tumors (74%), compared to G1 (57%), but these differences were not significant on multivariable Cox regression analyses (HR:1.6; 95% CI [0.8-3.2]). During follow-up, 15 (17.5%) vs. 18 (21.2%) vs. 10 (11.5%) patients underwent 1 vs. 2 vs. ≥3 PSS. Moreover, 26 (30.6%) and 4 (4.7%) men were treated with glansectomy and partial/total penile amputation due to local progression, tumor size or patient preference. Additionally, 24 (28%) men underwent invasive nodal staging. Last, 22 (25.9%) patients experienced disease progression. Median (IQR) time to disease progression was 51 (31-82) months., Conclusion: Patients treated with PSS for newly diagnosed superficial or initially invasive squamous cell carcinoma of the penis should be informed about the non-negligible risk of tumor recurrence and disease progression over time. In consequence, strict follow-up protocols are needed., Competing Interests: Conflicts of interest None, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To develop a novel risk tool that allows the prediction of lymph node invasion (LNI) among patients with prostate cancer (PCa) treated with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND)., Methods: We retrospectively identified 742 patients treated with RARP + ePLND at a single center between 2012 and 2018. All patients underwent multiparametric magnetic resonance imaging (mpMRI) and were diagnosed with targeted biopsies. First, the nomogram published by Briganti et al. was validated in our cohort. Second, three novel multivariable logistic regression models predicting LNI were developed: (1) a complete model fitted with PSA, ISUP grade groups, percentage of positive cores (PCP), extracapsular extension (ECE), and Prostate Imaging Reporting and Data System (PI-RADS) score; (2) a simplified model where ECE score was not included (model 1); and (3) a simplified model where PI-RADS score was not included (model 2). The predictive accuracy of the models was assessed with the receiver operating characteristic-derived area under the curve (AUC). Calibration plots and decision curve analyses were used., Results: Overall, 149 patients (20%) had LNI. In multivariable logistic regression models, PSA (OR: 1.03; P= 0.001), ISUP grade groups (OR: 1.33; P= 0.001), PCP (OR: 1.01; P= 0.01), and ECE score (ECE 4 vs. 3 OR: 2.99; ECE 5 vs. 3 OR: 6.97; P< 0.001) were associated with higher rates of LNI. The AUC of the Briganti et al. model was 74%. Conversely, the AUC of model 1 vs. model 2 vs. complete model was, respectively, 78% vs. 81% vs. 81%. Simplified model 1 (ECE score only) was then chosen as the best performing model. A nomogram to calculate the individual probability of LNI, based on model 1 was created. Setting our cut-off at 5% we missed only 2.6% of LNI patients., Conclusions: We developed a novel nomogram that combines PSA, ISUP grade groups, PCP, and mpMRI-derived ECE score to predict the probability of LNI at final pathology in RARP candidates. The application of a nomogram derived cut-off of 5% allows to avoid a consistent number of ePLND procedures, missing only 2.6% of LNI patients. External validation of our model is needed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The NCCN guidelines recommend active surveillance (AS) as an option for the initial management of cT1a 0-2 cm renal lesions. However, data about comparison between renal cell carcinoma (RCC) 0-2 cm vs. 2.1-4 cm are scarce., Methods: Within the Surveillance, Epidemiology, and End Results database (2002-2016), 46,630 T1a N any M any stage patients treated with nephrectomy were identified. Data were tabulated according to histological subtype, tumor grade (low [LG] vs. high [HG]), as well as age category and gender. Additionally, rates of synchronous metastases were quantified., Results: Overall, 69.3 vs. 74.1% clear cell, 21.4 vs. 17.6% papillary, 6.9 vs. 6.8% chromophobe, 2.0 vs. 1.1% sarcomatoid dedifferentiation, 0.2 vs. 0.2% collecting duct histological subtype were identified for respectively 0-2 cm and 2.1-4 cm RCCs. In both groups, advanced age was associated with higher rate of HG clear cell and HG papillary histological subtype. In 0-2 cm vs. 2.1-4 cm RCCs, 13.8% vs. 20.2% individuals operated on harbored HG tumors and were more prevalent in males. Lower synchronous metastases rates were recorded in 0-2 cm RCC and ranged from 0 in respectively multilocular cystic to 0.9% in HG papillary histological subtype. The highest synchronous metastases rates were recorded in sarcomatoid dedifferentiation histological subtype (13.8% and 9.7%) in both groups., Conclusions: Relative to 2.1-4 cm RCCs, 0-2 cm RCCs harbored lower rates of HG tumors, lower rates of aggressive variant histology and lower rates of synchronous metastases. The indications and demographics of patients selected for AS may be expanded in the future to include younger and healthier patients., (Copyright © 2021. Published by Elsevier Inc.)

Background: The increased awareness regarding the sex gap in bladder cancer (BCa) care over the last decade may have resulted in more timely-wise referral patterns and treatment of female patients with BCa. Thus, we tested the association of sex with disease stage at presentation, as well as with cancer-specific mortality (CSM) after radical cystectomy (RC) in a contemporary cohort of patients with nonmetastatic urothelial bladder cancer (UCUB)., Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 14,086 patients (10,879 men and 3,207 women) treated with RC for non-metastatic UCUB. Temporal trend, interaction analyses, logistic regression, cumulative incidence, and competing-risks regression analyses were used., Results: Overall, 10,879 (77.2%) men and 3,207 (22.8%) women underwent RC between 2004 and 2016. Female gender was an independent predictor of non-organ-confined (NOC) UCUB at RC in multivariable analyses (odds ratio: 1.23; 95% confidence intervals [CI] 1.10-1.38; P < 0.001). While NOC rates in men decreased over time (from 54.8% to 45.7%; P < 0.01), NOC rates in women remained stationary (from 60.6% to 57.3%; P = 0.15) and the excess NOC rate between men and women increased from + 5.8% in 2004 to +11.6% in 2016. Moreover, in multivariable analyses adjusted for other covariates, female gender was an independent predictor of higher CSM after RC in NOC UCUB (HR: 1.14; 95%CI 1.04-1.24; P < 0.01), but not in localized UCUB (P = 0.06)., Conclusion: It is worrisome that, while in men the rate of NOC is decreasing, NOC rates in females have not improved over time. Moreover, it is also worrisome that, despite adjustment for both pathological tumor and patient characteristics, female sex remains an adverse prognostic factor for CSM. Reassessment of referral, diagnostic, and treatment patterns aimed at eliminating these sex discrepancies appears warranted., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The Albumin-Globulin Ratio (AGR; albumin/total protein - albumin) has been associated with oncological outcome in various malignancies. However, its role in urothelial carcinoma of the bladder (UCB) has not been clearly established. In this study, we assessed the association of preoperative AGR (pAGR) with survival in patients who underwent radical cystectomy (RC) for UCB., Material and Methods: We conducted a retrospective analysis of an established multicenter database of 4.335 patients who were treated with RC for UCB. The cohort was divided into 2 groups according to the pAGR status. Binominal logistic regression as well as uni- and multivariable Cox regression analyses were used. The predictive value of the models was assessed by calculating receiver operating characteristics curves and concordance-indices (C-Index). The additional clinical value was assessed using the decision curve analysis (DCA)., Results: Overall, 1.670 patients (38.5%) had a low pAGR. On multivariable logistic regression analyses, low pAGR was associated with an increased risk of ≥pT3 disease at RC (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01-1.31, P= 0.04). On multivariable Cox regression analyses, low pAGR remained associated with worse recurrence-free survival (RFS, HR 1.24, 95% CI 1.1-1.37, P< 0.001), cancer-specific survival (CSS, HR 1.23, 95% CI 1.1-1.38, P< 0.001) and overall survival (OS, HR 1.17, 95% CI 1.07-1.28, P< 0.001). The addition of pAGR to multiple prognostic models that were respectively fitted for clinical and postoperative variables did not improve the predictive accuracy., Conclusion: pAGR status is an independent predictor of ≥pT3 disease, therefore it could help identify patients who have a higher likelihood to benefit from neoadjuvant systemic therapy. While pAGR was independently associated with RFS, CSS, and OS, it did not improve the predictive accuracy and clinical value beyond obtained by information already available. The predictive value of this biomarker in the age of immunotherapy needs further evaluation., Competing Interests: Conflicts of interest All authors have no conflict of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Radical cystectomy (RC) is often performed for T1 variant histology bladder cancer (VHBC), based on weak clinical evidence. We tested for cancer specific survival (CSS) differences after RC between T1 VHBC vs. urothelial carcinoma of the urinary bladder (UBC)., Methods: Within the Surveillance, Epidemiology and End Results registry (SEER, 2001-2016), we retrospectively identified T1N0M0 VHBC (adenocarcinoma, squamous cell carcinoma [SqCC], neuroendocrine carcinoma and other VHBC) and UBC patients. Kaplan-Meier plots, multivariate Cox regression models (CRM) with inverse probability treatment weighting (IPTW) and competing risks regression (CRR) tested CSS rates after RC in stage T1 vs. no-RC according to VHBC type and UBC., Results: Of all 37,528 T1N0M0 bladder cancer patients, 1726 (4.6%) harboured VHBC. Of those, 598 (1.6%) had SqCC, 409 (1.1%) adenocarcinoma, 249 (0.7%) neuroendocrine carcinoma and 470 (1.3%) other VHBC. RC was performed in 7.4-11.0% of VHBC vs. 5.1% of high grade UBC patients. In patients with neuroendocrine and SqCC, RC was associated with higher CSS rates than any other surgical treatment modality (both p ≤ 0.01). Sixty-month CSS was 100% vs. 67% in neuroendocrine and 86% vs. 66% in SqCC in unadjusted analyses and remained statistically significantly higher in multivariate, IPTW adjusted analyses and in multivariate CRR. No difference was recorded for adenocarcinoma or other VHBC types., Conclusions: RC for stage T1N0M0 VHBC appears to provide a protective effect with respect to CSS in patients with SqCC and neuroendocrine carcinoma, but not in adenocarcinoma or other VHBC., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To assess contemporary gender, race and stage-specific incidence and trends of bladder cancer among young adults in the United States., Materials and Methods: Within Surveillance, Epidemiology, and End Results database (2001-2016), all patients aged 20 to 39 years-old with histologically confirmed bladder cancer were included. Age-standardized rates (ASR per 100,000 person-years) were estimated. Temporal trends were calculated through joinpoint regression analyses to describe the average annual percent change (AAPC)., Results: From 2000 to 2016, 2,772 new cases were recorded (ASR 0.2, AAPC -1.5%, P = 0.01). ASRs were higher in males than in females (0.3 and 0.1, respectively) and decreased significantly in both genders (AAPC -1.3, P = 0.02 and -2.2% P = 0.03, respectively). non-Hispanic White (NHW) accounted for 70.7% of the cohort and had the highest incidence (ASR 0.3) that decreased over time (AAPC -1.4%, P = 0.02). Conversely, ASRs in other ethnic groups were lower and showed stable trends. The most frequent tumor characteristics were Ta/TisN0M0 stage (71.0%, ASR 0.1, AAPC -1.0%, P = 0.1), low grade (61.6%, ASR 0.1, AAPC -4.3%, P = 0.001) and urothelial histology (95.5%, ASR 0.2, AAPC -1.5%, P = 0.01)., Conclusions: Despite the rarity of bladder cancer in those aged 20 to 39 years, a standard work-up is required to avoid advanced stage at diagnosis. The current data validate initial diagnoses at earliest stage in the vast majority of young adults. Moreover, decreasing ASRs in both genders are encouraging., Competing Interests: Conflict of interest All the authors declare no potential conflict of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To test international society of urological pathology grade group (ISUP GG) concordance rates between multiparametric magnetic resonance imaging (mpMRI) targeted biopsies (TB) vs. standard systematic biopsies (SB) and radical prostatectomy (RP) specimens, in biopsy naïve patients., Materials and Methods: This retrospective single center study included 80 vs. 500 biopsy naïve patients diagnosed with TB vs. SB and treated with RP between 2015 and 2018. First, we compared ISUP GG concordance rates and the percentages of undetected clinically significant prostate cancer (csPCa: ISUP GG  ≥ 3), between TB vs. SB and RP. Second, multivariable logistic regression models tested predictors of concordance rates before and after 1:3 propensity score (PS) matching. Third, among TB patients, univariable logistic regression models tested variables associated with ISUP GG concordance at RP., Results: Overall, ISUP GG concordance rates were, respectively, 55 vs. 41.4% for TB vs. SB (P = 0.02). However, no differences in concordance rates were observed in patients with biopsy ISUP GG1 (31 vs. 33.9% for TB vs. SB; P = 0.8). Moreover, 15 vs. 18.8% csPCa were missed by TB vs. SB, respectively (P = 0.4). In multivariable logistic regression models, TB were associated with higher concordance rates before (odds ratio [OR]: 1.13; P = 0.04) and after 1:3 PS matching (OR: 1.15; P 0.03), compared to SB. In TB patients, age (OR: 0.98; P = 0.04), maximum cancer core involvement (MCCI; OR: 1.02; P = 0.02) and maximum cancer core length (MCCL; OR: 1.01; P = 0.07) were associated with ISUP GG concordance. Moreover, a trend for lower concordance rates was observed with higher PSA-D (OR: 0.77; P = 0.1). Finally, intermediate lesion location at mpMRI was associated with lowest concordance rates (44%)., Conclusion: In biopsy naïve patients treated with RP, TB achieved higher rates of ISUP GG concordance, but same percentages of csPCa missed, compared to SB. Moreover, only patients with ISUP GG ≥2, but not patients with ISUP GG1, exhibited higher concordance rates. Finally, age, MCCI, MCCL, PSA-D, and lesion location were associated with concordance between TB and RP., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Identifying which patients are likely to benefit from cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is important. We tested the association between preoperative serum De Ritis ratio (DRR, Aspartate Aminotransferase/Alanine Aminotransferase) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN., Material and Methods: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment DRR cut-off value, we found 1.2 to have the maximum Youden index value. The overall population was therefore divided into 2 DRR groups using this cut-off (low, <1.2 vs. high, ≥1.2). Univariable and multivariable Cox regression analyses tested the association between DRR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the DRR was evaluated with decision curve analysis., Results: Among 613 mRCC patients, 239 (39%) patients had a DRR ≥1.2. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high DRR was significantly associated with OS (hazard ratios [HR]: 1.22, 95% confidence interval [CI]: 1.01-1.46, P = 0.04) and CSS (HR: 1.23, 95% CI: 1.02-1.47, P = 0.03). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, high DRR remained significantly associated with both OS (HR: 1.26, 95% CI: 1.04-1.52, P = 0.02) and CSS (HR: 1.26, 95% CI: 1.05-1.53, P = 0.01). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.633 vs. C-index = 0.629). On decision curve analysis, the inclusion of DRR did not improve the net-benefit beyond that obtained by established subgroup analyses stratified by IMDC risk groups, type of systemic therapy, body mass index and sarcomatoid features, did not reveal any prognostic value to DRR., Conclusion: Despite the statistically significant association between DRR and OS as well as CSS in mRCC patients treated with CN, DRR does not seem to add any further prognostic value beyond that obtained by currently available features., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We investigated the association between synchronous metastases (SMs), histologic subtype (HS), tumor size (TS), and tumor grade (TG) in surgically treated stage T2 renal cell carcinoma (RCC)., Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2005-2015), 8344 patients with T2 RCC who had undergone radical nephrectomy were identified. The SM rates were tabulated according to the HS, TG, and TS and tested in multivariable logistic regression models., Results: According to the HS, the average SM rates were 0%, 1.4%, 4.6%, 6.4%, 12.7%, 20.0%, and 32.7% for multilocular cystic, chromophobe, papillary, TG 1-2 clear cell, TG 3-4 clear cell, collecting duct, and sarcomatoid dedifferentiation RCC, respectively. In multivariable logistic regression models predicting for SMs, HS represented the strongest predictor, followed by TG, TS, and race. When combined, HS, TG, TS, and race predicted for SMs with 70.2% accuracy compared with 62.5% with HS, 60.2% with TG, 57.8% with TS, and 53.0% with race alone. Lung only was the most common metastatic site (43.6%), followed by bone only (27.6%), liver only (4.4%), and brain only (4.4%). Of all the patients with SMs, 78.9% had a single metastatic site., Conclusions: The SM rates showed very wide variation according to the HS, TG, and TS. When HS was combined with TG, TS, and race, SMs could be accurately predicted in individual patients better than with TS alone. Thus, renal mass biopsy-derived HS and TG could improve the prediction of SMs compared with using TS alone., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to test the effect of chemotherapy and/or radical cystectomy (RC) and/or radiotherapy (RT) on survival of patients with non-metastatic small-cell carcinoma of the urinary bladder (SCCUB)., Materials and Methods: Within the Surveillance, Epidemiology, and End Results registry (2001-2016), we identified patients with non-metastatic (T1-4, N0, M0) SCCUB. Treatment was defined as: chemotherapy alone, chemotherapy + RC, and chemotherapy + RT. Temporal trends, cumulative incidence plots, and multivariable competing risks regression models were used., Results: Of 595 patients with SCCUB, 230 (38.5%), 159 (27%), and 206 (34.5%) were treated with chemotherapy alone, chemotherapy + RC, and chemotherapy + RT, respectively. The rates of chemotherapy + RC increased (estimated annual percentage changes [EAPC], +5.9%; P = .002). Conversely, chemotherapy alone (EAPC, -1.7%; P = .1) and chemotherapy + RT rates decreased (EAPC: -2.2%; P = .08). Overall, 5-year cancer-specific mortality (CSM) rates were 44%, 29%, and 40% for patients treated with chemotherapy alone, chemotherapy + RC, and chemotherapy + RT, respectively (P = .004). Relative to chemotherapy alone, patients treated with chemotherapy + RC experienced lower CSM (hazard ratio, 0.5; P < .001). Conversely, patients treated with chemotherapy + RT did not exhibit any CSM benefit (hazard ratio, 0.8; P = .2), when compared with chemotherapy alone., Conclusion: In contemporary patients with SCCUB with non-metastatic disease, the rates of chemotherapy + RC are increasing. Conversely, the rates of combined chemotherapy with RT and chemotherapy alone are decreasing. These patterns of treatment are in agreement with better cancer control in patients with SCCUB. In consequence, until more robust data become available, the combination of chemotherapy and RC should represent the recommended treatment strategy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The burden of renal cell carcinoma (RCC) in young adults received marginal attention. We assessed contemporary gender, race and stage-specific incidence and trends of RCC among young adults (20-39 years-old) in the United States., Methods: Within Surveillance, Epidemiology, and End Results database (2000-2016), patients aged 20-39 years with histologically confirmed RCC were included. Age-standardized incidence rates (ASR per 100,000 person-years) were estimated. Temporal trends were calculated through joinpoint regression analyses to describe the average annual percent change (AAPC)., Results: From 2000-2016, 7767 new RCC cases were recorded (ASR 0.6, AAPC  + 5.0 %, p < 0.001). ASRs were higher in males than in females (0.7 and 0.5, respectively) and increased significantly in both genders (AAPC + 5.0 % and +4.7 % both p < 0.001, respectively). Non-Hispanic American Indian/Alaska Native had the highest incidence (ASR 1.0) vs. non-Hispanic Asian or Pacific Islander the lowest (ASR 0.3). ASRs significantly increased in all ethnic groups. T1aN0M0 and T1bN0M0 stages showed the highest incidence and increase (ASR 0.3, AAPC + 5.9 %, p < 0.001 and ASR 0.1, AAPC + 5.7 %, p < 0.001, respectively). Also regional and distant stages increased (AAPC + 3.7 %, p = 0.001 and AAPC + 1.5 %, p = 0.06). The most frequent tumor characteristics were G2 (44.4 %, ASR 0.3, AAPC + 6.3 %, p < 0.001) and G1 (13.1 %, ASR 0.1, AAPC + 1.1 %, p = 0.2), as well as clear cell histology (54.8 %, ASR 0.3, AAPC  + 7.6 %, p < 0.001)., Conclusions: RCC in young adults is rare, but increasing. This is mainly due to T1aN0M0 tumors. Nonetheless, also regional diseases are significantly increasing. Differences between ethnic groups exist and may warrant further research., Competing Interests: Declaration of Competing Interest All the authors declare no potential conflict of interest to disclose, (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: We tested whether frail patients may benefit from robot-assisted (RARC) relative to open radical cystectomy (ORC)., Materials and Methods: Frail patients treated with RC were identified within the National Inpatient Sample database (2008-2015). The effect of RARC vs. ORC was tested in five separate multivariable models predicting: complications, failure to rescue (FTR), in-hospital mortality, length of stay (LOS) and total hospital charges (THCs). As internal validity measure, analyses were repeated among non-frail patients. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics., Results: Of 11,578 RC patients, 3477 (30.0%) were frail. RARC was performed in 488 (14.0%) frail patients and 1386 (17.1%) non-frail patients. Among frail, RARC was only independently associated with shorter LOS (median 8 vs. 9 days, relative ratio [RR] 0.79, p < 0.001). Conversely, among non-frail, RARC was independently associated with lower complications (57.3 vs. 59.1%, odds ratio [OR] 0.82, p = 0.004) and shorter LOS (median 6 vs. 7 days, RR 0.88, p < 0.001), but also predicted higher THCs (+2850.3 US dollars, p = 0.001)., Conclusions: In frail patients, the use of RARC did not result in better short-term outcomes except for one-day advantage in LOS. Conversely, in non-frail patients, the use of RARC resulted in lower complication rates and shorter LOS at the cost of higher THCs. In consequence, the benefit of RARC appears relatively marginal in frail patients and our data do not suggest a clear and clinically-meaningful benefit of RARC over ORC in frail radical cystectomy population., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

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 <0.01) and for ccRCC (EAPC: -1.0%; P <0.01), (2) rates of G3/G4 decreased for non-ccRCC (EAPC: -0.7%; P = 0.03), but increased for ccRCC (EAPC: +1.1; P <0.01), 3) rates of node positive disease decreased for non-ccRCC (EAPC:-3.1%; P = 0.02), but were stable for ccRCC (EAPC: +0.4; P =0.5), (4) rates of metastatic disease at diagnosis decreased for non-ccRCC (EAPC: -3.2%; P <0.01), but were stable for ccRCC (EAPC: -0.6%; P = 0.1), (5) among non-ccRCC, the percentage of papRCC increased (EAPC:+1%; P <0.01), while the percentage of sarcRCC (EAPC: -7%; P <0.01) and cdRCC (EAPC: -11.2%; P <0.01) decreased. Finally, in multivariable CRR models, lower CSM was recorded for contemporary non-ccRCC (HR: 0.7; P <0.001) and ccRCC (HR: 0.8; P <0.001) patients., Conclusion: Our findings illustrate a favorable stage and grade migration and improved cancer-specific mortality in contemporary non-ccRCC. Additionally, despite absence of meaningful stage migration in ccRCC, improved cancer-specific mortality in contemporary patients was also recorded. In consequence, a 2-tiered process appears to be operational in non-ccRCC vs. a 1-tiered phenomenon in ccRCC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict of interest All authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The present study tested cancer-specific (CSM) and overall mortality (OM) after partial cystectomy (PC) for variant histology bladder cancer (non-urothelial carcinoma of the urinary bladder UCUB), relative to UCUB and relative to radical cystectomy (RC)., Materials and Methods: Within the Surveillance, Epidemiology, and End Results registry (2001-2016), we identified patients with stage T1-T2N0M0 non-UCUB and UCUB who had undergone PC or RC. Non-UCUB included adenocarcinoma, squamous carcinoma, neuroendocrine carcinoma, and other histologic subtypes. First, CSM and OM after PC were compared between the non-UCUB and UCUB groups. Second, CSM and OM after PC were compared with RC in the non-UCUB group. Kaplan Meier plots and multivariable Cox regression models were used before and after inverse probability of treatment weighting., Results: Overall, 248 patients (16.3%) treated with PC had had non-UCUB. Of the 248 cases, 115 (46.5%), 50 (20%), 34 (14%), and 49 (19.5%) were adenocarcinoma, squamous carcinoma, neuroendocrine carcinoma, and other histologic subtypes, respectively. The comparison between PC in the non-UCUB and PC in the UCUB group showed higher CSM (hazard ratio, 1.4; P = .03) but the same OM rates (hazard ratio, 1.1; P = .7) in the non-UCUB group. The comparison between PC and RC for the non-UCUB group showed no CSM or OM differences., Conclusions: PC for non-UCUB was associated with higher CSM compared with PC for UCUB. However, PC instead of RC for select patients with non-UCUB appears not to undermine cancer-control outcomes. Thus, the excess CSM is probably unrelated to cystectomy type but could originate from differences in the tumor biology. These results could act as hypothesis generating for the design of future trials., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: We investigated the effect of partial cystectomy (PC) on cancer-specific mortality (CSM) and other-cause mortality (OCM) and the effect of pelvic lymph node dissection (PLND) during PC on CSM., Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2015), 11,429 cases of nonmetastatic stage pT2-T3 urothelial carcinoma of the urinary bladder treated with either PC or radical cystectomy (RC) were identified. All comparisons between PC and RC relied on propensity score (PS; ratio, 1:1) adjusted univariable and multivariable logistic and competing risks regression models. In contrast, all comparisons between PLND and no PLND at PC relied on inverse probability of treatment weighting-adjusted univariable and multivariable Cox regression models., Results: Within the SEER database, PC had been performed in 979 patients (8.6%). The PC annual rates decreased from 11.0% to 6.8% during the study period (P < .001). In PS-adjusted multivariable analyses focusing on CSM and OCM, no statistically significant difference between the PC and RC groups (P = .2 and P = .3, respectively). The annual PLND rates with PC (50.3%) did not vary over time (P = .3). In the overall cohort and the PC subgroup, PLND was associated with a lower CSM rate (hazard ratio, 0.56; P < .001; and hazard ratio, 0.57; P < .001, respectively)., Conclusions: A small proportion of patients with stage pT2-T3 urothelial carcinoma of the urinary bladder were candidates for PC. In the PS-adjusted multivariable analyses, no statistically significant differences were found in CSM or OCM between the PC and RC groups. Within the PC group, PLND had been omitted 50% of the time despite its association with lower CSM., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Unmarried status is an established risk factor for worse cancer control outcomes and survival in various malignancies. We tested the effect of marital status on the rate of nonorgan confined disease as well as on cancer-specific mortality (CSM) in patients who underwent radical cystectomy for nonmetastatic urothelial bladder cancer (UCUB)., Methods: Within the Surveillance, Epidemiology and End Results database (2007-2015), we identified 11,167 patients (8,639 men and 2,528 women) who underwent radical cystectomy for nonmetastatic UCUB. Temporal trend analyses, logistic regression models, cumulative incidence plots, competing-risks regression models and landmark analyses were used., Results: Overall, 2,454 men (28.4%) and 1,363 women (53.9%) were unmarried. Unmarried men had a higher rate of nonorgan-confined disease at radical cystectomy (OR: 1.24, CI 1.10-1.33; P < 0.001). Moreover, in men, unmarried status was an independent predictor of higher CSM (HR: 1.24, CI 1.12-1.37) In women, unmarried status neither predicted nonorgan-confined disease at radical cystectomy (OR: 1.07, CI 0.91-1.26; P = 0.37) nor was it associated with CSM (HR: 1.13, CI 0.88-1.31; P = 0.14). In 6-month landmark analyses, unmarried status remained an independent predictor of higher CSM in men (HR: 1.20, CI 1.08-1.33)., Conclusions: Unmarried men have more advanced tumor stage at radical cystectomy and worse CSM compared to married men. Interestingly, marital status did not affect oncologic outcomes in women. These data suggest a gender-specific effect of marital status in UCUB., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Our objective was to test whether the rates of perioperative chemotherapy (CHT) administration in patients with urothelial bladder cancer (UCUB) with prostatic stromal invasion (pT4a) changed over time. Moreover, we tested the effect of CHT on overall mortality (OM), as well as on cancer-specific mortality (CSM) in this patient population., Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 1513 men with non-metastatic UCUB with prostatic stromal invasion who underwent radical cystectomy with lymph node dissection, with or without CHT administration. Estimated annual percentage change analyses, inverse probability of treatment-weighting (IPTW), Kaplan-Meier plots, Cox regression models, and landmark analyses were performed., Results: Overall, 732 (48.4%) patients with pT4a UCUB disease underwent radical cystectomy with perioperative CHT administration between 2004 and 2016. The CHT administration rate increased from 29.0% in 2004 to 64.8% in 2016 (P < .001). In IPTW-adjusted analyses, the 5-year overall survival was 47.7% versus 39.8%, and cancer-specific survival was 53.6 versus 50.1%, for with versus without CHT administration, respectively. After multivariable and IPTW-adjusted Cox regression models, administration of CHT independently predicted lower OM (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.52-0.73), as well as lower CSM (HR, 0.66; 95% CI, 0.55-0.80). even after 3-month landmark analyses (OM HR, 0.64; 95% CI 0.54-0.76; CSM HR, 0.70; 95% CI, 0.58-0.85)., Conclusions: The use of CHT in patients with pT4a UCUB increased from low to moderate in the most contemporary era. However, based on its impressive reduction in OM, as well as in CSM, further increases in CHT administration rates should be highly encouraged in this patient population., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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 < .001), as corroborated in multivariable Cox regression models., Conclusions: OCM rates were highest in oldest individuals and in African-American men. In both groups, an important 5-year OCM reduction over the 25-year study span was recorded. Nonetheless, these 2 patient groups may still represent the ideal target for better patient selection based on OCM considerations, because their most recent OCM rates exceeded those of, respectively, younger and Caucasian patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Few data examined the potential survival benefit of nephroureterectomy (NU) in the setting of metastatic upper urinary tract urothelial carcinoma (mUTUC). We hypothesized that a survival benefit might be associated with the use of NU in that setting and tested this hypothesis within a large population-based cohort., Patients and Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2014), we identified 1174 patients with mUTUC. Kaplan-Meier plots, as well as multivariable Cox regression models (MCRMs), relying on inverse probability after treatment weighting and landmark analyses, were used to test the effect of NU versus no surgical treatment on cancer-specific mortality (CSM) in patients with mUTUC., Results: Of 1174 patients with mUTUC, 449 (38%) underwent NU. The rate of NU decreased over time from 47.1% to 34.6% (estimated annual percentage change, -4%; P = .006]. In MCRMs, NU achieved independent predictor status for lower CSM (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.46-0.66; P < .001). In MCRMs stratified according to chemotherapy, NU also achieved independent predictor status for lower CSM, both in patients who received (n = 597; 50.9%) (HR, 0.68; 95% CI, 0.53-0.87; P = .002) or did not receive (n = 574; 49%) (HR, 0.44; 95% CI, 0.33-0.58; P < .001) chemotherapy. Virtually the same results were recorded after inverse probability after treatment weighting adjustment, as well as in landmark analyses., Conclusions: Our analyses suggest a potential survival benefit after NU in the setting of mUTUC, regardless of chemotherapy administration., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To understand the multiparametric magnetic resonance imaging (mpMRI) interreader agreement between radiologists of peripheral and academic centers and the possibility to avoid prostate biopsies according to magnetic resonance imaging second opinion., Patients and Methods: This prospective observational study enrolled 266 patients submitted to mpMRI at nonacademic centers for cancer detection or at active surveillance begin. Images obtained were reviewed by 2 unblinded radiologists with 8 and 5 years' experience on mpMRI, respectively. We recorded Prostate Imaging Reporting and Data System (PI-RADS) v2 categories and management strategy changes after mpMRI rereadings. Interreader agreement was assessed by the Cohen kappa. For mpMRI second opinion, positive predictive value and negative predictive value were calculated., Results: In the original readings, no lesions (ie, PI-RADS < 2) were observed in 17 cases (6.5%). Reported index lesion (IL) PI-RADS category was 2 in 23 (8.5%), 3 in 85 (32%), 4 in 98 (37%), and 5 in 13 (5%) men, respectively. It is noteworthy that in 30 examinations (11%), an IL was recognized by radiologists, but a suspicious score was not assigned. According to first reading of mpMRI, initial clinical strategy included performing a targeted (226; 85%) or a systematic biopsy (8; 3%), scheduling the patient to an active surveillance program without repeat biopsy (10; 4%), or monitoring prostate-specific antigen without prostate sampling (22; 8%). The mpMRI rereads did not change IL PI-RADS category in 91 cases (38.5%), although in 20 (8.5%) and 125 (53%) IL PI-RADS was upgraded or downgraded, respectively (κ = 0.23). The clinical management changed in 113 patients (48%) (κ = 0.2). Overall, 102 targeted biopsies (51%) were avoided and 72 men (34.5%) were not submitted to biopsy after mpMRI second opinion. Positive predictive value and negative predictive value of the mpMRI rereading were 58% and 91%, respectively. Major limitations of the study are limited-time follow-up and the lack of a standard of reference for some men, who were not submitted to biopsy according to mpMRI second opinion., Conclusion: There is an important level of discordance between mpMRI reports. According to imaging second opinion, roughly half of targeted biopsies could be avoidable and 34.5% of men could skipped prostate sampling. Prospective randomized trials are needed to confirm our findings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Objectives: Enhanced recovery after surgery protocols (ERAS) have been developed and implemented as of 2001. However, no previous analyses targeted length of stay (LOS) changes over time after major surgical oncological procedures (MSOPs)., Methods: Between 2003 and 2013, we retrospectively identified patients, who underwent prostatectomy, colectomy, cystectomy, mastectomy, gastrectomy, hysterectomy, nephrectomy, oophorectomy, lung resection or pancreatectomy within the Nationwide Inpatient Sample. A total of 3 431 602 assessable patients were identified. We examined temporal trends of LOS after ten MSOPs, as well as LOS determinants and the impact of LOS on total hospital charges (THCGs). Univariable and multivariable linear, log-linear, logistic (MLR) and Poisson regression (MPR) analyses were used., Results: Mean and median LOS were respectively 6 and 4 days (IQR 2-7). During the study span, LOS decreased [Estimated annual percentage change (EAPC): -1.89%, p = 0.0002]. Of the ten examined MSOPs, nine showed a decrease that ranged from -4.47% in prostatectomy to -0.7% in mastectomy. Conversely, no decrease in LOS was recorded for colectomy (EAPC:+0.37, p = 0.015). In MPR analyses, robotic [Relative risk (RR):0.68, p = 0.0003] and laparoscopic (RR: 0.90, p < 0.0001) surgical approaches were associated with shorter LOS. LOS was directly related to THCGs., Conclusions: Since the implementation of ERAS protocols, LOS has decreased for nine out of ten MSOPs in a significant fashion. Although these gains may appear marginal on an annual basis, their cumulative effect, over the study span, ranges for 7.7%-49.2%, which can hardly be interpreted as marginal. LOS decrease directly translates in THCGs savings., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Patients with clinical T4 (cT4) bladder cancer (BCa) infrequently undergo radical cystectomy (RC). We investigated the reliability of preoperative clinical staging, perioperative and survival outcomes in patients treated with RC due to cT4a-b BCa disease at a single tertiary care institution., Methods: The study relied on 917 BCa patients treated with RC and pelvic lymph node dissection (PLND) at a single institution between January 1995 and December 2012. We compared the accuracy of the clinical assessment with final pathology results. Moreover, we evaluated perioperative outcomes, complication rates and survival after surgery., Results: The median follow-up was 62 months. Overall, 74 (8.1%) patients presented cT4 stage at preoperative evaluation. Conversely, a pathological T4 disease was confirmed only in 68.9% patients staged initially as cT4. No differences were recorded in complications, 30 days readmission or 30 days death rates between cT1-T3 vs. cT4a vs. cT4b (p > 0.1). At multivariable Cox regression analyses predicting cancer specific mortality, clinical T4 stage vs. clinical T1-2, clinical T3 stage vs. clinical T1-2 and age were predictors of worst survival after RC (all p < 0.04)., Conclusions: We recorded poor concordance between preoperative imaging and pathology in cT4 patients. No differences in major perioperative outcomes and acceptable survival expectancies were reported in patients treated for cT4 disease., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: We evaluated the effect of the year of surgery on the clinical, pathologic, and oncologic outcomes of patients with bladder cancer (BCa) treated with radical cystectomy (RC) at a single institution., Materials and Methods: The present study included 1253 consecutive patients with BCa treated with RC and extended pelvic lymphadenectomy at a single institution from January 1990 to December 2014. Analysis of variance and χ 2 trend tests were used to report the clinical and pathologic characteristics of the cohort over time. Multivariable Cox regression analysis was used to test the relationship between the year of surgery and recurrence, cancer-specific mortality (CSM) and overall mortality (OM)., Results: Considering the clinical characteristics, patient age (P = .1) and gender (P = .2) remained steady during the study period. In contrast, the body mass index (P < .005) increased. Also, of the pathologic features, carcinoma in situ detection (P < .001) showed an increasing rate, and pathologic stage T3-T4 (P = .005) showed a decreasing trend. The number of lymph nodes removed increased during the study period (P < .001), resulting in an increased number of positive nodes (P < .001). However, the rate of lymph node invasion (P = .1) remained stable in the overall population. Multivariable Cox regression analyses revealed the year of surgery as a predictor of recurrence (hazard ratio [HR], 0.97), CSM (HR, 0.97), and OM (HR, 0.98), with a slight, but constant, reduction in all survival outcomes (P < .04 for all)., Conclusion: Changes were recorded considering the patient and tumor characteristics across the previous 25 years. These variations directly reflect the differences in long-term survival expectations we recorded., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To evaluate the incidence and predictors of 30-day readmission in prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP)., Patients and Methods: Overall, 1402 consecutive PCa patients treated with RARP at a single center between 2006 and 2013 were identified. Uni- and multivariate logistic regression analyses assessed predictors of 30-day readmission after surgery., Results: Overall, 38 patients (2.7%) experienced hospital readmission within 30 days after discharge. The most common causes of rehospitalization were fever in 12 patients (31.6%), lymphoceles in 11 (28.9%), and urine leak in 6 (15.8%). By multivariable analyses, D'Amico risk group and occurrence of postoperative complications (odds ratio [OR], 2.89) represented independent predictors of 30-day readmission (all P ≤ .02). When analyzing the type of complication associated with the risk of readmission, fever (OR, 6.19; P = .01), urine leak (OR, 10.83; P < .01) and cardiocirculatory complications (OR, 18.57; P < .001) were significantly associated with 30-day readmission., Conclusion: Patients undergoing RARP have a relatively low risk of 30-day readmission (2.7%). The occurrence of an early postoperative complication and a higher D'Amico risk group were independent predictors of 30-day readmission. In addition, fever, urine leak, and cardiocirculatory complications are significantly associated with a higher risk of readmission., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Despite several studies, the adequate management of positive distal ureter margins at the time of radical cystectomy (RC) remains controversial. Particularly, it is not clear whether the achievement of negative distal ureter margins at the intraoperative frozen sections (IFS) affects postoperative cancer-specific mortality (CSM)., Methods: In all, 1,447 consecutive patients treated with RC at a single center between January 1987 and August 2014 were considered. Multivariable (MVA) logistic regression analyses were used to determine predictors of positive IFS. MVA Cox regression analyses were used to test the effect on CSM of intraoperative conversion to negative margins., Results: At IFS, 368 patients (25%) experienced at least 1 positive margin. Of these, a negative conversion of the margin at IFS occurred in 178 (48%) whereas 190 (52%) had a positive final ureteral margin. The mean follow-up was 95 months (median = 102). At MVA, history of carcinoma in situ (odds ratio = 6.40, P<0.001) was predictors of positive margin at IFS. At MVA, ureteral margins that were not converted to negative (hazard ratio = 1.92, P = 0.01) were associated with CSM but only in patients with negative soft tissue margin and without node metastases., Conclusions: Achieving negative IFS margins may be associated with survival benefit in patients without residual bladder cancer after RC. Patients who recorded a history of carcinoma in situ before RC are at higher risk to incur positive ureteral margin at IFS and should be investigated during RC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Previous studies have demonstrated that perioperative blood transfusion (BT) is associated with a significantly increased risk of cancer recurrence and mortality after radical cystectomy (RC). Recently, it was shown for the first time that intraoperative transfusion has a detrimental effect on cancer survival. The aim of the current study was to validate this finding in a single European institution., Patients and Methods: The study focused on 1490 consecutive nonmetastatic bladder cancer patients treated with RC at a single tertiary care referral center between January 1990 and August 2013. Kaplan-Meier analyses and Cox regression analyses were used to assess the effect of timing of BT administration (no transfusion vs. intraoperative transfusion vs. postoperative transfusion vs. intraoperative and postoperative transfusion) on cancer-specific mortality (CSM), overall mortality (OM), and disease recurrence., Results: Mean age at the time of RC was 67 years. Overall, 322 (21.6%) patients received intraoperative BT and 97 (6.5%) received postoperative BT. At a mean follow-up time of 125 months (median, 110 months), the 5- and 10-year CSM rate was 846 (58%) and 715 (48%), respectively. In multivariable analyses patients who received intraoperative BT had greater risk of disease recurrence (hazard ratio [HR], 1.24; P < .04), CSM (HR, 1.60; P < .02), and OM (HR, 1.45; P < .03). Conversely, this effect disappears with postoperative BT (all P > .2)., Conclusion: Our study confirms that intraoperative, but not postoperative BT, are related to a detrimental effect on survival after RC. These results should be take into account by physicians to administer BT using the correct timing., (Copyright © 2015 Elsevier Inc. All rights reserved.)