Unlocking the Potential of Adequate Bacillus Calmette-Guérin Immunotherapy in Very-high-risk Non–muscle-invasive Bladder Carcinoma: A Multicenter Analysis of Oncological Outcomes and Risk Dynamics

background : the european association of urology (EAU) recommends discussing upfront radical cystectomy for all patients with very high risk (VHR) non-muscle-invasive bladder carcinoma (NMIBC), but the role of bacillus calmette-guérin (BCG) treatment remains controversial. objective: to analyze oncological outcomes in VHR NMIBC patients (EAU risk groups) treated with adequate BCG. design, setting,and partecipants: a multi-institutional retrospective study involving patients with VHR NMIBC who received adequate BCG therapy from 2007 to 2020 was conducted. outcomemeasurements and statisticalanalysis: a survival analysis estimated recurrence-free survival (RFS), progression-free survival (PFS), and the cumulative incidence of cancer-specific mortality (CSM) after accounting for other causes of mortality as competing risk events and of the overall mortality (OM). conditional survival probabilities for 0-4 yr without events were computed. cox regression assessed the predictors of oncological outcomes. results and limitation: a total of 640 patients, with a median 47 (32-67) mo follow-up for event-free individuals, were analyzed. high-grade RFS and PFS at 5 yr were 53% (49-57%) and 78% (74-82%), respectively. the cumulative incidence of CSM and OM at 5 yr was 13% (10-16%) and 16% (13-19%), respectively. conditional RFS, PFS, overall survival, and cancer-specific survival at 4 yr were 91%, 96%, 87%, and 94%, respectively. cox regression identified tumor grade (hazard ratio [HR]: 1.54; 1.1-2) and size (HR: 1.3; 1.1-1.7) as RFS predictors. tumor multiplicity predicted RFS (HR: 1.6; 1.3-2), PFS (HR: 2; 1.2-3.3), and CSM (HR: 2; 1.2-3.2), while age predicted OM (HR: 1.48; 1.1-2). conclusion: patients with VHR NMIBC who receive adequate BCG therapy have a more favorable prognosis than predicted by EAU risk groups, especially among those with a sustained response, in whom continuing maintenance therapy emerges as a viable alternative to radical cystectomy. patient summary: our research shows that a sustained response to bacillus calmette-guérin in patients can lead to favorable outcomes, serving as a viable alternative to cystectomy for select cases.