Boorjian, Stephen A.

Objective To validate International Bladder Cancer Group (IBCG) definitions of Bacillus Calmette‐Guérin (BCG)‐unresponsive and BCG‐exposed non‐muscle‐invasive bladder cancer (NMIBC) and assess prognostic heterogeneity across various BCG‐failure types. Patients and Methods From a multicentre international cohort of 3806 BCG‐treated patients, 591 who developed high‐grade NMIBC recurrence following BCG between 2003 and 2024 were included. Progression‐free survival (PFS) was the primary endpoint; cancer‐specific (CSM) and overall mortality (OM) were secondary endpoints. Cumulative incidence functions, competing‐risk models and multivariable Cox regression were used. Results Patients with BCG‐unresponsive and BCG‐exposed disease showed similar PFS, CSM, and OM (all P > 0.05). When stratified into five subgroups, prognosis varied: 5‐year progression rates were 29% for BCG‐unresponsive, 32.5% for late relapse (between 6 and 24 months) after adequate BCG, 30% for BCG‐exposed with inadequate BCG (<24 months from induction), 6.2% for BCG‐resistant, and 14% for very late relapse (>24 months since last BCG) ( P < 0.01). In multivariable analysis, BCG‐exposed after inadequate BCG (subdistribution hazard ratio [sHR] 3.42, 95% confidence interval [CI] 1.33–8.84), late relapse (sHR 3.74, 95% CI 1.59–8.78), and BCG‐unresponsive (sHR 2.34, 95% CI 1.00–5.44) were associated with higher progression risks compared to very late relapse. Limitations include retrospective design and treatment heterogeneity. Conclusions Under IBCG definitions, BCG‐unresponsive and BCG‐exposed NMIBC have similarly poor outcomes. A refined classification reveals prognostic heterogeneity, with late relapses after adequate BCG demonstrating outcomes comparable to BCG‐unresponsive, and very late relapses conferring better prognosis.

ABSTRACT Introduction Non‐muscle invasive bladder cancer (NMIBC) is a chronic disease with a lifelong treatment burden that may cause substantial urinary morbidity. Such quality‐of‐life changes remain understudied. We therefore evaluated the incidence and predictors of treatment for overactive bladder (OAB) among older adults following diagnosis of NMIBC. Materials and Methods We identified adults aged 66–89 years with newly diagnosed NMIBC from 2007 to 2017 in the linked SEER‐Medicare database. We examined the incidence of treatment initiation for OAB following initial transurethral resection of bladder tumor (TURBT) and evaluated associations with baseline characteristics using Cox regression. Results We identified 9,819 patients, of whom 68% had Ta disease, 29% had T1 disease, and 4% had CIS. Within the first 12 months of TURBT, 7% of patients received treatment for OAB, and this increased to 15% of patients at 5 years. In the first year, the most utilized therapies were anticholinergic medications (early 3.72%, late 2.74%) and beta‐3 agonists (early 0.11%, late 0.32%), while procedural OAB therapy utilization was rare (0.2%). On multivariable analysis, female gender (HR 1.26, 95% CI 1.11–1.42), congestive heart failure (HR 1.21, 95% CI 1.03–1.43), and T1 tumor stage (HR 1.27, 95% CI 1.12–1.44 vs. Ta) were independently associated with an increased risk of OAB treatment. Conclusions The incidence of OAB requiring treatment among patients with NMIBC is substantial, with approximately one in six patients receiving treatment by 5 years after diagnosis. Predictive clinicopathologic features for OAB treatment—including, sex, high‐risk tumor features, and repeat TURBT—may be useful for clinical counseling.

Abstract Objectives Sarcomatoid urothelial carcinoma (sUC) is associated with poor clinical outcomes. Herein, we evaluated clinicopathologic features (including PD-L1 expression) for institutional cases. Methods Sixty-five patients with sUC treated by radical cystectomy were matched for age, sex, and pathologic stage to 190 patients with pure urothelial carcinoma (UC). Outcomes were evaluated using the Kaplan-Meier method. Immunohistochemistry (IHC) results for tumor-specific PD-L1 expression in sUC were quantified using H-scores (range, 0-300). Cases with constitutive PD-L1 expression (cPD-L1; H-score ≥240) were evaluated for amplification events using fluorescence in situ hybridization (n = 28), mate-pair sequencing (Mpseq; n = 6), RNA sequencing (n = 5), and targeted next-generation sequencing (n = 8). PD-L1 regulatory pathways were evaluated using gene set enrichment analysis in the Cancer Hallmark dataset. Results Most patients with sUC had advanced disease (≥pT2, 62/65, 95%), without significant differences in overall and cancer-specific survival, when matched to pure UC. Median PD-L1 H-scores using different clones were 100 (SP142), 120 (SP263), and 195 (22C3). cPD-L1 was seen in 43% (28/65) of cases of sUC that were enriched for TP53, TERT, and CDKN2A/B alterations. PD-L1 amplification was identified in 7 (of 28, 25%) of these cases. Bionformatics analysis consistently identified IL6-JAK-STAT3 and interferon α/γ signaling in sUC with cPD-L1 expression. Conclusions Our results suggest that cPD-L1 expression in most sUC occurs secondary to IL6-JAK-STAT3 and interferon α/γ signaling. This provides a biologic rationale for evaluating response to immunotherapy in this patient population.

Purpose: Surgical video review can be used in urologic training, yet significant barriers to the implementation of video review programs exist, and formal assessment of usage and utility for trainees is limited. Here, we evaluate a novel video review platform to describe patterns of use and determine perceived utility. Materials and Methods: We analyzed learning points entered by trainees during video review of radical prostatectomy cases using our surgical intelligence–enabled Film Room platform between September 2023 and July 2024. Learning point content was categorized according to surgical coaching domains as technical, cognitive, nontechnical, or descriptive. Entries were compared by surgical step and level of training. Anonymous surveys were distributed to trainees to determine perceived utility and reveal patterns of video review. Results: Thirteen trainees entered 480 unique learning points across all radical prostatectomy steps and spanning surgical coaching domains during the study period. Learning points varied by training level, with junior trainees entering points more often than senior trainees for Retzius-space dissection ( N = 73 vs 17, p < 0.01) and seminal vesicle and posterior dissection ( N = 58 vs 27, p < 0.01). Trainees used video review in preparation for both upcoming cases and performance analysis. Ninety-four percent of survey respondents reported they either agreed or strongly agreed that video review helped them develop surgical skills. Conclusions: We found usage across training levels and high perceived utility of our Film Room platform for video review of robotic prostatectomy. Implementation of video review platforms holds promise to augment existing urologic training and should be explored further.