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

• DOI: 10.1016/j.euo.2024.01.017
• Publication Date: 2024-02-13T20:20:54Z
• Authors: José Daniel Subiela; Wojciech Krajewski; Daniel A. Gonzále...; Jan Laszkiewicz; Javier Taborda; Júlia Aumatell; Miguel Sanchez En...; Giuseppe Basile; Marco Moschini; Jorge Caño-Velasco; Enrique Lopez Perez; Pedro Del Olmo Durán; Andrea Gallioli; Andrzej Tukiendorf; David D'Andrea; Jeremy Yuen-Chun ...; Alejandra Serna C...; Renate Pichler; Luca Afferi; Francesco Del Giu...; Juan Gomez Rivas; Simone Albisinni; Francesco Soria; Guillaume Ploussard; Laura S. Mertens; Paweł Rajwa; Ekaterina Laukhtina; Benjamin Pradere; Karl Tully; Félix Guerrero-Ramos; Óscar Rodríguez-Faba; Mario Alvarez-Mae...; Jose Luis Domingu...; Tomasz Szydełko; Victoria Gomez Do...; Miguel Ángel Jimé...; Francisco Javier ...
• Keywords: Bacillus Calmette-Guérin; Non–muscle-invasive bladder carcinoma; Very high risk; Non–muscle-invasive bladder carcinoma; Bacillus Calmette-Guérin; Settore MEDS-14/C - Urologia; 610; Very high risk

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.To analyze oncological outcomes in VHR NMIBC patients (EAU risk groups) treated with adequate BCG.A multi-institutional retrospective study involving patients with VHR NMIBC who received adequate BCG therapy from 2007 to 2020 was conducted.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.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).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.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.