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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.)

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.)

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: 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.)

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: 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: 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.)