Radical cystectomy vs bladder-sparing therapy in very high-risk non–muscle-invasive bladder cancer: Real-world 5-year outcomes and immune checkpoint inhibitor–based substrategy analysis.

Abstract

e16610 Background: While early radical cystectomy (RC) is recommended by contemporary guidelines for very high-risk non–muscle-invasive bladder cancer (VHR-NMIBC), a substantial proportion of patients are not ideal candidates for RC or decline surgery; therefore, bladder-sparing therapy (BST) approaches remain clinically relevant, including intravesical BCG and emerging immune checkpoint inhibitor–based (ICI-based) strategies in BCG-naïve NMIBC. However, follow-up data on ICI-based strategies in BCG-naïve NMIBC remain limited. Therefore, we compared 5-year survival outcomes of RC vs BST and examined BST substrategies, focusing on whether ICI-based approach improves intravesical control. Methods: This multi-center retrospective cohort (2019–2025) included patients with pathologically confirmed very high-risk NMIBC per EAU risk stratification across 13 medical centers in China. Treatments were RC (± pelvic lymph node dissection) or BST (ICI-based systemic therapy or intravesical BCG). Endpoints were 5-year progression-free survival (PFS; ≥T2 progression, regional/distant metastasis, or death), cancer-specific survival (CSS), and intravesical recurrence–free survival (IVRFS; intravesical recurrence [Ta/T1/CIS], persistent disease on re-TURBT, or death before intravesical failure). Kaplan–Meier estimated 5-year rates. Multivariable Cox models adjusted for age, sex, stage (Ta/T1), CIS, tumor size/multifocality, and variant histology. Results: Among 379 patients, 186 received RC and 193 received BST (ICI-based n = 93; BCG n = 100). Median follow-up was 62.3 months (reverse KM; 95%CI 60.07–64.17). RC vs BST showed no significant differences: 5-year PFS 94.0% vs 87.5% (HR 0.59, 95%CI 0.23–1.40, P = 0.44); CSS 95.7% vs 95.7% (HR 1.65, 95%CI 0.52–5.24, P = 0.84); IVRFS 87.1% vs 82.2% (HR 0.99, 95%CI 0.48–2.00, P = 0.87). Within BST, ICI-based vs BCG demonstrated no significant differences in PFS and CSS but significantly improved IVRFS: PFS 89.0% vs 87.6%; CSS 96.9% vs 97.0%; IVRFS 67.5% vs 60.5% (HR 0.34, 95%CI 0.17–0.69, P = 0.003). Compared with RC, ICI-based BST showed no significant differences in PFS, CSS, or IVRFS (all P > 0.05), with a 5-year bladder preservation rate of 93.78%. Conclusions: In this real-world cohort of patients with BCG-naïve very high-risk NMIBC, RC and BST had broadly similar 5-year PFS, CSS, and IVRFS. Within BST, while maintaining similar PFS and CSS, an ICI-based strategy provided significantly better intravesical recurrence disease control than BCG, supporting ICI-based BST as a meaningful bladder-preserving option for selected patients.