Cisplatin eligibility in the neoadjuvant setting of patients with muscle-invasive bladder cancer undergoing radical cystectomy.

BACKGROUND: To examine the agreement of different calculated estimated glomerular filtration rate (eGFR) formulas and measured creatinine clearance (CrCI) at the primary diagnosis of muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We performed a multicenter analysis of patients with MIBC, treated with cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), or with RC alone, between 2011 and 2021. Baseline eGFR was computed using 4 calculated serum equations including Cockcroft-Gault (CG), MDRD, CKD-EPI 2009, and race-free CKD-EPI 2021. To examine the association between calculated eGFR and measured CrCI, subgroup analyses were performed among patients in whom measured 24-hour urine CrCl was determined. Cisplatin-ineligibility was defined as CrCI and/or eGFR < 60 mL/minute per 1.73 m2. RESULTS: Of 956 patients, 30.0%, 33.3%, 31.9%, and 27.7% were found to be cisplatin-ineligible by the CG, MDRD, CKD-EPI, and race-free CKD-EPI equations (P = .052). The concordance between calculated eGFR formulas was rated substantial (Cohen's kappa (k): 0.66-0.95). Among the subgroup (n = 245) with measured CrCl, 37 (15.1%) patients had a CrCI less than 60 mL/minute. Concordance between measured CrCl and calculated eGFR was poor (ĸ: 0.29-0.40). All calculated eGFR formulas markedly underestimated the measured CrCI. Specifically, 78%-87.5% of patients with a calculated eGFR between 40 and 59 mL/minute exhibited a measured CrCI ≥ 60 mL/minute. CONCLUSIONS: Comparing calculated eGFR formulas, similar percentages of patients with MIBC were deemed cisplatin-ineligible. However, a significant number of patients could be upgraded by being cisplatin-fit based on measured CrCI, particularly when the calculated eGFR was falling within the gray range of 40-59 mL/minute.

Global burden, risk factors, and temporal trends of ureteral cancer: a comprehensive analysis of cancer registries.

BACKGROUND: Ureteral cancer is a rare cancer. This study aimed to provide an up-to-date and comprehensive analysis on the global trends of ureteral cancer incidence and its association with lifestyle and metabolic risk factors. METHODS: The incidence of ureteral cancer was estimated from the Cancer Incidence in Five Continents Plus and Global Cancer Observatory databases. We analyzed the (1) global incidence of ureteral cancer by region, country, sex, and age group by age-standardized rates (ASR); (2) associated risk factors on a population level by univariable linear regression with logarithm transformation; and (3) incidence trend of ureteral cancer by sex and age group in different countries by Average Annual Percentage Change (AAPC). RESULTS: The global age-standardized rate of ureteral cancer incidence in 2022 was 22.3 per 10,000,000 people. Regions with higher human development index (HDI), such as Europe, Northern America, and East Asia, were found to have a higher incidence of ureteral cancer. Higher HDI and gross domestic product (GDP) and a higher prevalence of smoking, alcohol drinking, physical inactivity, unhealthy dietary, obesity, hypertension, diabetes, and lipid disorder were associated with higher incidence of ureteral cancer. An overall increasing trend of ureteral cancer incidence was observed for the past decade, especially among the female population. CONCLUSIONS: Although ureteral cancer was relatively rare, the number of cases reported was rising over the world. The rising trends among females were more evident compared with the other subgroups, especially in European countries. Further studies could be conducted to examine the reasons behind these epidemiological changes and confirm the relationship with the risk factors identified.

Addition of neoadjuvant chemotherapy to a 'quadrifecta' composite in radical cystectomy.

OBJECTIVES: To evaluate the impact of incorporating neoadjuvant chemotherapy (NAC) into the 'quadrifecta' outcomes composite for reporting outcomes of radical cystectomy (RC) creating a pentafecta score. PATIENTS AND METHODS: This is a retrospective multicentre analysis of patients treated with RC, with or without NAC, for bladder cancer between 2002 and 2023. The primary outcome was the effect of adding NAC to a quadrifecta outcomes composite on cancer-specific (CSS) and overall survival (OS). The quadrifecta outcomes composite included a yield of ≥16 lymph nodes, negative soft tissue surgical margin, absence of major complication within 30 days from surgery, and no delay in RC. RESULTS: A total of 590 patients were included in the analyses. A total of 233 (39.5%) patients achieved all quadrifecta outcomes and 82 (13.9%) patients were additionally treated with NAC, achieving the pentafecta. Achieving the quadrifecta outcomes composite was significantly associated with better CSS (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.32-0.75; P = 0.001) and OS (HR 0.48, 95% CI 0.34-0.69; P < 0.01). The addition of NAC to the quadrifecta composite outcomes significantly improved the discrimination of patients more likely to have better CSS (HR 0.21, 95% CI 0.08-0.57; P = 0.002) and OS (HR 0.26, 95% CI 0.12-0.55; P < 0.01). CONCLUSION: We propose a new pentafecta that may serve as a tool for standardising outcomes reporting and measuring the quality of RC.

Adjuvant intravesical therapy in intermediate-risk non-muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. PATIENTS AND METHODS: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. RESULTS: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). CONCLUSION: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.

Urinary function in female patients after traditional, organ-sparing and nerve-sparing radical cystectomy for bladder cancer: a systematic review and pooled analysis.

OBJECTIVES: To determine and summarize the available data on urinary, sexual, and health-related quality-of-life (HRQOL) outcomes after traditional radical cystectomy (RC), reproductive organ-preserving RC (ROPRC) and nerve-sparing RC (NSRC) for bladder cancer (BCa) in female patients. METHODS: The PubMed, SCOPUS and Web of Science databases were searched to identify studies reporting functional outcomes in female patients undergoing RC and urinary diversion for the treatment of BCa. The outcomes of interest were voiding function (for orthotopic neobladder [ONB]), sexual function and HRQOL. The following independent variables were derived and included in the meta-analysis: pooled rate of daytime and nighttime continence/incontinence, and intermittent self-catheterization (ISC) rates. Analyses were performed separately for traditional, organ- and/or nerve-sparing surgical approaches. RESULTS: Fifty-three studies comprising 2740 female patients (1201 traditional RC and 1539 organ-/nerve-sparing RC, and 264 nerve-sparing-alone RC) were eligible for qualitative synthesis; 44 studies comprising 2418 female patients were included in the quantitative synthesis. In women with ONB diversion, the pooled rates of daytime continence after traditional RC, ROPRC and NSRC were 75.2%, 79.3% and 71.2%, respectively. The pooled rate of nighttime continence after traditional RC was 59.5%; this rate increased to 70.7% and 71.7% in women who underwent ROPRC and NSRC, respectively. The pooled rate of ISC after traditional RC with ONB diversion in female patients was 27.6% and decreased to 20.6% and 16.8% in patients undergoing ROPRC and NSRC, respectively. The use of different definitions and questionnaires in the assessment of postoperative sexual and HRQOL outcomes did not allow a systematic comparison. CONCLUSIONS: Female organ- and nerve-sparing surgical approaches during RC seem to result in improved voiding function. There is a significant need for well-designed studies exploring sexual and HRQOL outcomes to establish evidence-based management strategies to support a shared decision-making process tailored towards patient expectations and satisfaction. Understanding expected functional, sexual and quality-of-life outcomes is necessary to allow individualized pre- and postoperative counselling and care delivery in female patients planned to undergo RC.

Vesical Imaging-Reporting and Data System use predicting the outcome of neoadjuvant pembrolizumab in muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the predictive capability of the pre- and post-pembrolizumab Vesical Imaging-Reporting and Data System (VI-RADS) to identify ypT0N0 or ypT≤1N0 response in muscle-invasive bladder cancer (MIBC) within the PURE-01 trial (ClinicalTrials.gov identifier: NCT02736266). PATIENTS AND METHODS: Patients were staged with bladder multiparametric magnetic resonance imaging (mpMRI) before and after treatment (three cycles of pembrolizumab) prior to radical cystectomy (RC). Logistic regression models were used to analyse the pre- and post- pembrolizumab VI-RADS against ypT≤1N0 and ypT0N0 response. The VI-RADS scores were dichotomised between 0 and 3 (0 = no evidence of disease) and 4-5. Event-free survival (EFS) and overall survival (OS) analyses were performed. Comprehensive genomic profiling and transcriptome-wide expression profiling data were matched with the VI-RADS scores. RESULTS: In total, 110 patients underwent centrally reviewed scans (N = 220 mpMRI), treated between February 2017 and July 2020. Both pre- and post-pembrolizumab VI-RADS 0-3 scores were the only significant covariates that predicted the ypT≤1N0 endpoint in multivariable analyses, and the strongest effect was seen with post-pembrolizumab VI-RADS 0-3 predicting the ypT≤1N0 response (P < 0.001). The area under the curve for this model was 0.90. Post-pembrolizumab VI-RADS 0-3 also predicted a longer EFS (P < 0.001) and OS (P = 0.044). The scores of several gene signatures from baseline tumours differed between the pre-pembrolizumab VI-RADS 0-3 and 4-5 categories. CONCLUSION: Post-pembrolizumab VI-RADS scores are strongly associated with pathological downstaging and survival. VI-RADS scores were also characterised by distinct biomarker features. These results indicate that the VI-RADS is emerging as an important tool for designing next-generation trials for MIBC.

Use of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) PET/CT for lymph node assessment before radical cystectomy in bladder cancer patients.

OBJECTIVE: To assess the diagnostic performance of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomograpy (PET)/computed tomography (CT) in nodal staging before radical cystectomy (RC) and pelvic lymph node dissection (PLND) for bladder cancer (BCa). MATERIALS AND METHODS: This analysis was based on a cohort of 199 BCa patients undergoing RC and bilateral PLND between 2015 and 2022. Neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) was administered after oncological evaluation. All patients received preoperative 18F-FDG PET/CT to assess extravesical disease. Point estimates for true negative, false negative, false positive, true positive, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of conventional imaging and PET/CT were calculated. Subgroup analysis in patients receiving neoadjuvant treatment was performed. RESULTS: At preoperative evaluation, 30 patients (15.1%) had 48 suspicious nodal spots on 18F-FDG PET/CT. At RC and bilateral PLND, a total of 4871 lymph nodes (LNs) were removed with 237 node metastases corresponding to 126 different regions. Pathological node metastases were found in 17/30 (57%) vs 39/169 patients (23%) with suspicious vs negative preoperative 18F-FDG PET/CT, respectively (sensitivity = 0.30, specificity = 0.91, PPV = 0.57, NPV = 0.77, accuracy = 0.74). On per-region analysis including 1367 nodal regions, LN involvement was found in 19/48 (39%) vs 105/1319 (8%) suspicious vs negative regions at PET/CT, respectively (sensitivity = 0.15, specificity = 0.98, PPV = 0.40, NPV = 0.92, ACC = 0.90). Similar results were observed for patients receiving NAC (n = 44, 32.1%) and NAI (n = 93, 67.9% [per-patient: sensitivity = 0.36, specificity = 0.91, PPV = 0.59, NPV = 0.80, accuracy = 0.77; per-region: sensitivity = 0.12, specificity = 0.98, PPV = 0.32, NPV = 0.93, ACC = 0.91]). Study limitations include its retrospective design and limited patient numbers. CONCLUSIONS: In eight out of 10 patients with negative preoperative 18F-FDG PET/CT, pN0 disease was confirmed at final pathology. No differences were found based on NAC vs NAI treatment. These findings suggest that 18F-FDG PET/CT could play a role in the preoperative evaluation of nodal metastases in BCa patients, although its cost-effectiveness is uncertain.

Trimodal therapy effect on survival in urothelial vs non-urothelial bladder cancer.

OBJECTIVE: To address cancer-specific mortality free-survival (CSM-FS) differences in patients with urothelial carcinoma of the urinary bladder (UCUB) vs non-UCUB who underwent trimodal therapy (TMT), according to organ confined (OC: T2N0M0) vs non-organ confined (NOC: T3-4NanyM0 or TanyN1-3M0) clinical stages. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with cT2-T4N0-N3M0 bladder cancer treated with TMT, defined as the combination of transurethral resection of bladder tumour, chemotherapy, and radiotherapy. Temporal trends described TMT use over time. Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM in UCUB vs non-UCUB according to OC vs NOC stages. RESULTS: Of 5130 assessable TMT-treated patients, 425 (8%) harboured non-UCUB vs 4705 (92%) who had UCUB. The TMT rates increased for patients with OC UCUB from 92.4% to 96.8% (estimated annual percentage change of 0.4%, P < 0.001), but not in the NOC stages (P = 0.3). In the OC stage, the median CSM-FS was 36 months in patients with non-UCUB vs 60 months in those with UCUB, respectively (P = 0.01). Conversely, in the NOC stage, the median CSM-FS was 23 months both in UCUB and non-UCUB (P = 0.9). In the MCR models addressing OC stage, non-UCUB histology independently predicted higher CSM (hazard ratio 1.45, P = 0.004), but not in the NOC stage (P = 0.9). CONCLUSION: In OC UCUB, TMT rates have increased over time in a guideline-consistent fashion. Patients with OC non-UCUB treated with TMT showed a CSM disadvantage relative to OC UCUB. In the NOC stage, use of TMT resulted in dismal CSM, regardless of UCUB vs non-UCUB histology.

Impact of the extent of lymph node dissection on survival outcomes in clinically lymph node-positive bladder cancer.

OBJECTIVE: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.

The optimal number of induction chemotherapy cycles in clinically lymph node-positive bladder cancer.

OBJECTIVE: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. PATIENTS AND METHODS: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni- and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer-specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. RESULTS: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2-year OS estimates were 63% (95% confidence interval [CI] 0.53-0.74) and 63% (95% CI 0.58-0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni- or multivariable Cox regression analyses. CONCLUSION: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding.

OBJECTIVES: To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding. RESULTS: In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation. CONCLUSIONS: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.

Robotic-assisted radical cystectomy with cutaneous ureterostomies: a contemporary multicenter analysis.

BACKGROUND: Robotic-assisted radical cystectomy (RARC) offers decreased blood loss during surgery, shorter hospital length of stay, and lower risk for thromboembolic events without hindering oncological outcomes. Cutaneous ureterostomies (UCS) are a seldom utilized diversion that can be a suitable alternative for a selected group of patients with competing co-morbidities and limited life expectancy. OBJECTIVE: To describe operative and perioperative characteristics as well as oncological outcomes for patients that underwent RARC + UCS. METHODS: Patients that underwent RARC + UCS during 2013-2023 in 3 centers (EU = 2, US = 1) were identified in a prospectively maintained database. Baseline characteristics, pathological, and oncological outcomes were analyzed. Descriptive statistics and survival analysis were performed using R language version 4.3.1. RESULTS: Sixty-nine patients were included. The median age was 77 years (IQR 70-80) and the median follow-up time was 11 months (IQR 4-20). Ten patients were ASA 4 (14.5%). Nine patients underwent palliative cystectomy (13%). The median operation time was 241 min (IQR 202-290), and the median hospital stay was 8 days (IQR 6-11). The 30-day complication rate was 55.1% (grade ≥ 3a was 14.4%), and the 30-day readmission rate was 17.4%. Eleven patients developed metastatic recurrence (15.9%), and 14 patients (20.2%) died during the follow-up period. Overall survival at 6, 12, and 24 months was 84%, 81%, and 73%, respectively. CONCLUSIONS: RARC + UCS may offer lower complication and readmission rates without the need to perform enteric anastomosis, it can be considered in a selected group of patients with competing co-morbidities, or limited life expectancy. Larger prospective studies are necessary to validate these results.

Peri- and post-operative outcomes of robot-assisted radical cystectomy after the implementation of the EAU guidelines recommendations for collecting and reporting complications at a high-volume referral center.

PURPOSE: No studies relied on a standardized methodology to collect postoperative complications after robot-assisted radical cystectomy (RARC). The aim of our study was to evaluate peri- and post-operative outcomes of patients undergoing RARC adhering to the European Association of Urology (EAU) recommendations for reporting surgical outcomes and using a long postoperative follow-up. MATERIALS AND METHODS: 246 patients who underwent RARC with intracorporal urinary diversion at a single tertiary referral center with a postoperative follow-up ≥ 1 year for survivors. Postoperative outcomes were collected prospectively by interviews done by medical doctors. Complications were scored using the Clavien-Dindo classification (CD), grouped by type and severity (severe: CD score ≥ 3). We described peri- and post-operative outcomes and complication chronological distribution. RESULTS: Overall, 16 (6.5%) and 225 patients (91%) experienced intraoperative and postoperative complications, respectively. Moreover, 139 (57%) experienced severe complications. The most common any-grade and severe complications were infectious (72%) and genitourinary (35%), respectively. Overall, 52% of complications (358/682) occurred within 10 days from surgery, and 51% of severe complications (106/207) occurred within 35 days. However, 13% of complications (90/682) and 28% of severe complications (59/207) occurred 3 months after surgery. The earliest complications were fever of unknown origins and paralytic ileus (median time-to-complication [mTTC]: 4 days), the latest complications were urinary tract infection (mTTC: 40 days) and hydronephrosis/ureteral obstruction (mTTC: 70 days). CONCLUSIONS: The rate of postoperative complications after RARC is > 90% when a standardized collection method and a long follow-up is implemented. These results should be used to identify potential areas of improvement and for preoperative patient counseling.

Adjuvant immunotherapy in patients with renal cell carcinoma and urothelial carcinoma: A systematic review and network meta-analysis.

Adjuvant immune checkpoint inhibitor therapies have radically altered the treatment landscape for renal cell carcinoma and urothelial carcinoma. However, studies have reported negative data regarding adjuvant immune checkpoint inhibitor therapies. Thus, this study aimed to assess the role of adjuvant immune checkpoint inhibitor therapy for both renal cell carcinoma and urothelial carcinoma. A systematic review and network meta-analysis were conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Multiple databases were searched for articles published as of February 2023. Studies were deemed eligible if they evaluated disease-free survival in patients with renal cell carcinoma and urothelial carcinoma receiving adjuvant immune checkpoint inhibitor therapy. Five studies met the inclusion criteria. In a network meta-analysis, pembrolizumab was shown to be the most effective regimen for patients with renal cell carcinoma, whereas nivolumab was found to be the most effective regimen for patients with urothelial carcinoma. Additionally, these results were consistently observed in a sub-analysis of the T stage. The present analysis provides findings that support the usefulness of adjuvant nivolumab therapy in urothelial carcinoma and adjuvant pembrolizumab therapy in renal cell carcinoma, in agreement with the currently available guidelines. However, the caveat is that the randomized controlled trials included in this analysis differed in important respects despite being similar in study design. Therefore, with these differences in mind, care needs to be taken when selecting patients for these immune checkpoint inhibitor therapies to maximize their benefits.

Survival outcomes of patients treated with local therapy for nonmetastatic prostate cancer with high prostate-specific antigen concentrations.

BACKGROUND: Patients with nonmetastatic prostate cancer (nmPCa) and high prostate-specific antigen (PSA) levels due to the high likelihood of metastasis pose a clinical dilemma regarding their optimal treatment and long-term outcomes after initial local therapy. We aimed to evaluate the oncologic outcomes of patients treated with radical prostatectomy (RP) or radiotherapy (RT) for nmPCa with high PSA levels. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with nmPCa who received RP or RT from 2004 through 2015. We included nmPCa patients with high PSA levels categorized as ≥50 and ≥98 ng/mL, the highest level recorded in SEER. We used the Kaplan-Meier method and Cox proportional hazards to analyze cancer-specific (CSS) and overall survival (OS). RESULTS: We included 6177 patients with nmPCa and PSA ≥ 50 ng/mL at diagnosis; 1698 (27%) had PSA ≥ 98 ng/mL. Of these, 1658 (26.8%) underwent RP and 4519 (73.16%) patients received primary RT. Within a median of 113 months (interquartile range 74-150 months), the 5- and 10-year CSS estimates were 92.3% and 81.5% respectively; 10-year OS was 61%. In the PSA ≥ 98 ng/mL subgroup 5- and 10-year CSS estimates were 89.2% and 76%, respectively. In multivariable analyses for CSS, ISUP grade group (p < 0.001), N stage (p < 0.001), treatment with RP (hazard ratio [HR] = 0.60, 95% confidence interval [CI] 0.43-0.83, p < 0.001), and patient's age (p < 0.05) were associated with improved CSS. In the whole cohort of patients with PSA ≥ 50 ng/mL and RP subgroup, PSA failed to retain its independent prognostic value for CSS. CONCLUSIONS: Patients treated with local therapy for nmPCa with very high PSA at diagnosis have relatively good long-term oncological outcomes. Therefore, among well-selected patients with nmPCa, high PSA levels alone should not preclude the use of radical local therapy. Potential selection bias limits inferences about the relative effectiveness of specific local therapies in this setting.

Psychological Health of Surgeons in a Time of COVID-19: A Global Survey.

OBJECTIVE: To assess the degree of psychological impact among surgical providers during the COVID-19 pandemic. SUMMARY OF BACKGROUND DATA: The COVID-19 pandemic has extensively impacted global healthcare systems. We hypothesized that the degree of psychological impact would be higher for surgical providers deployed for COVID-19 work, certain surgical specialties, and for those who knew of someone diagnosed with, or who died, of COVID-19. METHODS: We conducted a global web-based survey to investigate the psychological impact of COVID-19. The primary outcomes were the depression anxiety stress scale-21 and Impact of Event Scale-Revised scores. RESULTS: A total of 4283 participants from 101 countries responded. 32.8%, 30.8%, 25.9%, and 24.0% screened positive for depression, anxiety, stress, and PTSD respectively. Respondents who knew someone who died of COVID-19 were more likely to screen positive for depression, anxiety, stress, and PTSD (OR 1.3, 1.6, 1.4, 1.7 respectively, all P < 0.05). Respondents who knew of someone diagnosed with COVID-19 were more likely to screen positive for depression, stress, and PTSD (OR 1.2, 1.2, and 1.3 respectively, all P < 0.05). Surgical specialties that operated in the head and neck region had higher psychological distress among its surgeons. Deployment for COVID- 19-related work was not associated with increased psychological distress. CONCLUSIONS: The COVID-19 pandemic may have a mental health legacy outlasting its course. The long-term impact of this ongoing traumatic event underscores the importance of longitudinal mental health care for healthcare personnel, with particular attention to those who know of someone diagnosed with, or who died of COVID-19.

Surgical checklist adherence across urology expertise levels impacts transurethral resection of bladder tumour quality indicators.

OBJECTIVES: To address the association of perioperative surgical checklist across variable surgical expertise with transurethral resection of bladder tumour (TURBT) accuracy and oncological outcomes in non-muscle-invasive bladder cancer. PATIENTS AND METHODS: We relied on our prospective collaborative database of patients treated with TURBT between 2012 and 2017. Surgical experience was stratified into three groups: resident vs young vs expert consultants. The association of surgical experience with detrusor muscle (DM) presence and adherence to the standardised peri-procedural nine-items TURBT checklist was evaluated with logistic regression models. A Cox regression model was used to investigate the association of surgical experience with recurrence-free survival (RFS). RESULTS: A total of 503 patients were available for analysis. TURBT was performed by expert consultants in 265 (52.7%) patients, by young consultants in 149 (29.6%) and by residents in 89 (17.7%). Residents were more likely to have DM in the TURBT specimen than expert consultants (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.03-2.99, P = 0.04). Conversely, no differences in DM presence were seen between young vs expert consultants (OR 1.09, 95% CI 0.71-1.70, P = 0.69). The median checklist completion rate was higher for both residents and young consultants when compared to experts' counterparts (56% and 56% vs 44%, P = 0.009). When focusing on patients receiving a second-look TURBT, the persistent disease was associated with resident status (OR 4.24, 95% CI 1.14-17.70, P = 0.037) at initial TURBT. Surgical experience was not associated with 5-years RFS. CONCLUSION: Surgeon's experience in the case of adequate perioperative surgical checklist implementation was inversely associated with the presence of DM in the specimen but directly linked to higher probability of persistent disease at re-TURBT, although no 5-year RFS differences were noted.

Teaching robotic cystectomy: prospective pilot clinical validation of the ERUS training curriculum.

OBJECTIVE: To provide the first clinical validation of the European Association of Urology Robotic Urology Section (ERUS) curriculum for training in robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS AND METHODS: The ERUS proposed a structured curriculum, divided into 11 steps, to train novice surgeons and help overcome the steep learning curve associated with iRARC. In this study, one trainee completed the curriculum under the mentorship of an expert. Twenty-one patients were operated on by the trainee following the proposed iRARC curriculum [(t)iRARC group] and were compared with 42 patients treated with the standard of care by the mentor [(m)iRARC group]. To evaluate curriculum safety, peri-operative outcomes, surgical margins and complications were assessed. Propensity-score matching (1:2) was used to identify comparable (t)iRARC and (m)iRARC cases. Matched variables included age, body mass index, neoadjuvant therapy, American Society of Anesthesiologists score and cT stage. Mann-Whitney and chi-squared tests were used to compare peri- and postoperative outcomes between the two cohorts. To evaluate curriculum efficacy, steps attempted and completed by the trainee were assessed and studied as a function of growing surgical experience of the trainee. RESULTS: The trainee progressed in proficiency-based training through steps of increasing difficulty. No differences in estimated blood loss, positive soft tissue margins, number of resected lymph nodes, overall and high-grade complications, or 90-day readmissions between the (t)iRARC and (m)iRARC groups were observed (all P > 0.05). However, operating time was significantly longer in the (t)iRARC group (P = 0.01). Of the 209 available steps, the trainee attempted 168 (80%) and successfully performed 125 (60%). Increasing experience was associated with more steps being successfully performed (P < 0.001). CONCLUSIONS: The proposed ERUS curriculum assists naïve surgeons during the learning curve for iRARC and should be encouraged in order to guarantee optimal outcomes during the learning phase of this procedure.

Oncological impact of cystoscopic findings in non-muscle-invasive bladder cancer: a meta-analysis.

OBJECTIVE: To assess the association between cystoscopic findings and oncological outcomes in patients with non-muscle-invasive bladder cancer (NMIBC) given that the oncological impact of quantity and quality assessment of tumours with cystoscopy has not been well verified. METHODS: Multiple databases were queried in May 2022 for studies investigating the association of oncological outcomes, such as recurrence-free (RFS), progression-free (PFS), and cancer-specific survival (CSS), with cystoscopic findings, including multiplicity, size, and gross appearance of tumours in patients with NMIBC. RESULTS: Overall, 73 studies comprising 28 139 patients were eligible for the meta-analysis. Tumour multiplicity was associated with worse RFS (pooled hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.48-1.74) and PFS (pooled HR 1.44, 95% CI 1.18-1.76) in NMIBC patients (including both Ta and T1). Tumour size (≥3 cm) was associated with worse RFS (pooled HR 1.97, 95% CI 1.69-2.30) and PFS (pooled HR 1.81, 95% CI 1.52-2.15) in NMIBC patients. In patients with T1 bladder cancer (BCa), tumour multiplicity and size (≥3 cm) were also associated with worse RFS, PFS and CSS. By contrast, among patients treated with bacillus Calmette-Guérin (BCG), tumour multiplicity was not associated with worse RFS, and tumour size (≥3 cm) was not associated with worse PFS. Sessile tumours were associated with worse RFS (pooled HR 2.14, 95% CI 1.52-3.01) and PFS (pooled HR 2.17, 95% CI 1.42-3.32) compared to pedunculated tumours. Compared to papillary tumours, solid tumours were associated with worse RFS (pooled HR 1.84, 95% CI 1.25-2.72) and PFS (pooled HR 3.06, 95% CI 2.31-4.07) in NMIBC patients, and CSS in T1 BCa patients (pooled HR 2.32, 95% CI 1.63-3.30). CONCLUSIONS: Cystoscopic findings, including tumour multiplicity, size, and gross appearance, strongly predict oncological outcomes in NMIBC patients. Cystoscopic visual features can help in the decision-making process regarding the timeliness and extent of tumour resection as well as future management such as intravesical therapy.

Oncological and safety profiles in patients undergoing simultaneous transurethral resection (TUR) of bladder tumour and TUR of the prostate.

OBJECTIVES: To determine the oncological impact and adverse events of performing simultaneous transurethral resection of bladder tumour (TURB) and transurethral resection of the prostate (TURP), as evidence on the outcomes of simultaneous TURB for bladder cancer and TURP for obstructive benign prostatic hyperplasia is limited and contradictory. PATIENTS AND METHODS: Patients from 12 European hospitals treated with either TURB alone or simultaneous TURB and TURP (TURB+TURP) were retrospectively analysed. A propensity score matching (PSM) 1:1 was performed with patients from the TURB+TURP group matched to TURB-alone patients. Associations between surgery approach with recurrence-free (RFS) and progression-free (PFS) survivals were assessed in Cox regression models before and after PSM. We performed a subgroup analysis in patients with risk factors for recurrence (multifocality and/or tumour size >3 cm). RESULTS: A total of 762 men were included, among whom, 76% (581) underwent a TURB alone and 24% (181) a TURB+TURP. There was no difference in terms of tumour characteristics between the groups. We observed comparable length of stay as well as complication rates including major complications (Clavien-Dindo Grade ≥III) for the TURB-alone vs TURB+TURP groups, while the latest led to longer operative time (P < 0.001). During a median follow-up of 44 months, there were more recurrences in the TURB-alone (47%) compared to the TURB+TURP group (28%; P < 0.001). Interestingly, there were more recurrences at the bladder neck/prostatic fossa in the TURB-alone group (55% vs 3%, P < 0.001). TURB+TURP procedures were associated with improved RFS (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.29-0.53; P < 0.001), but not PFS (HR 1.63, 95% CI 0.90-2.98; P = 0.11). Within the PSM cohort of 254 patients, the simultaneous TURB+TURP was still associated with improved RFS (HR 0.33, 95% CI 0.22-0.49; P < 0.001). This was also true in the subgroup of 380 patients with recurrence risk factors (HR 0.41, 95% CI 0.28-0.62; P < 0.001). CONCLUSION: In our contemporary cohort, simultaneous TURB and TURP seems to be an oncologically safe option that may, even, improve RFS by potentially preventing disease recurrence at the bladder neck and in the prostatic fossa.