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

Abstract

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 participants

A multi-institutional retrospective study involving patients with VHR NMIBC who received adequate BCG therapy from 2007 to 2020 was conducted.

Outcome measurements and statistical analysis

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).

Conclusions

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.