Bladder preservation with disitamab vedotin plus PD-1 inhibitors and local intensification in muscle-invasive bladder cancer: a single-center retrospective cohort of 81 patients.

purposeTo evaluate the efficacy and safety of disitamab vedotin (DV) plus a PD-1 inhibitor combined with different local intensification strategies for the bladder-preserving management of muscle-invasive bladder cancer (MIBC).

methodsThis single-center retrospective cohort study enrolled patients with MIBC who underwent maximal transurethral resection of bladder tumor (TURBT), followed by DV plus a PD-1 inhibitor between January 1, 2023, and September 30, 2025. According to the local intensification strategy, patients were classified into three groups: group A, maximal TURBT followed by DV plus a PD-1 inhibitor; group B, maximal TURBT followed by DV plus a PD-1 inhibitor combined with intravesical Bacillus Calmette-Guérin (BCG); and group C, maximal TURBT followed by DV plus a PD-1 inhibitor combined with radiotherapy. Treatment selection was based on multidisciplinary evaluation of patients' clinical characteristics and treatment accessibility; because treatment allocation was nonrandomized, between-group comparisons were considered exploratory. The primary endpoint was bladder-intact event-free survival (BI-EFS). Secondary endpoints included clinical complete response (cCR), progression-free survival (PFS), overall survival (OS), bladder preservation rate, salvage or delayed radical cystectomy (RC) rate, and safety. Patient-level reasons for not receiving RC, conventional TMT, or radiotherapy were not uniformly documented, limiting assessment of treatment-selection bias.

resultsA total of 81 patients were included, comprising 41 in group A, 30 in group B, and 10 in group C. The median follow-up duration was 18.5 months (IQR, 13.7-26.6). The 12-month BI-EFS rates were 58.5%, 93.1%, and 90.0% in groups A, B, and C, respectively (P = 0.025). Compared with group A, group B showed improved BI-EFS (P = 0.002). In multivariable Cox regression analysis, group B was associated with a lower risk of BI-EFS events than group A (adjusted HR, 0.35; 95% CI 0.14-0.89; P = 0.027), while group C had a favorable but imprecise point estimate (adjusted HR, 0.31; 95% CI 0.07-1.40; P = 0.128). The cCR rates were 39.0%, 80.0%, and 60.0% in groups A, B, and C, respectively (P = 0.002), while the bladder preservation rates at the last follow-up were 75.6%, 100.0%, and 80.0%, respectively (P = 0.005). The 12-month PFS rates were 82.7%, 90.0%, and 100.0%, and the 12-month OS rates were 90.1%, 93.3%, and 100.0%, respectively. Any-grade and grade ≥ 3 adverse events occurred in 92.6% and 4.9% of patients, respectively; all four grade ≥ 3 events resulted in permanent discontinuation of ongoing DV plus PD-1 inhibitor therapy.

conclusionDV plus a PD-1 inhibitor combined with local intensification strategies was feasible for the bladder-preserving management of MIBC and demonstrated an acceptable overall safety profile. The addition of intravesical BCG was associated with improved bladder-intact outcomes. Group C also showed favorable 12-month BI-EFS, PFS, and OS estimates; however, its small sample size and wide confidence intervals preclude firm conclusions, and non-significance should not be interpreted as evidence of no radiotherapy benefit. These findings should be regarded as hypothesis-generating.