136 - Locoregional Recurrence in pT3-4/pN+ Muscle-Invasive Bladder Cancer Receiving Modern Perioperative Systemic Therapy: A Propensity Score-Matched Competing Risk Analysis

Purpose/Objective(s): Patients with pT3-4/pN+ muscle-invasive bladder cancer (MIBC) face significant risks of failure following radical cystectomy (RC). While modern systemic agents, including PD-1/L1 inhibitors and antibody-drug conjugates (ADCs), are increasingly utilized to improve survival, their specific impact on locoregional recurrence (LRR) remains inadequately defined. This study evaluated LRR patterns in high-risk patients receiving contemporary systemic therapy using a competing risk framework.

Materials/Methods: We retrospectively reviewed data from 446 consecutive pT3-4/pN+ MIBC patients at a single academic institution. LRR was defined as recurrence within the pelvic soft tissue or regional lymph nodes. A 1:1 propensity score matching (PSM) was utilized to balance cohorts based on age, sex, pathologic T/N stage, surgical margin status, and extent of lymph node dissection. The matched cohort comprised 167 pairs. In the systemic therapy group, 44.9% (75/167) received perioperative immunotherapy and/or ADCs. LRR was analyzed using the Fine-Gray subdistribution hazard model, treating distant metastasis and death as competing risks.

Results: Median follow-up was 25.3 months (95% CI: 22.1–29.8). Systemic therapy was associated with a lower cumulative incidence of distant metastasis or death (P = 0.043). However, the cumulative incidence of LRR was not significantly different between the groups (P = 0.409). The 2-year cumulative incidence of LRR was 28.5% (95% CI: 19.9–37.0%) in the systemic therapy group versus 29.3% (95% CI: 21.0–37.5%) in the RC-only group. In multivariable Fine-Gray regression adjusting for covariates, systemic therapy was not independently associated with a significant reduction in LRR (sHR = 0.775; 95% CI: 0.481–1.249; P = 0.30).

Conclusion: In pT3-4/pN+ MIBC, while modern perioperative systemic therapy effectively controls distant disease, no significant improvement in locoregional control was observed within the current follow-up period. These findings indicate that locoregional control remains a persistent challenge even in the era of immunotherapy and ADCs, suggesting that adjuvant radiotherapy may still be required to optimize outcomes for high-risk patients.

Abstract 136 - Table 1. Cumulative Incidence of Locoregional Recurrence (LRR) and Distant Metastasis (DM) at 24 Months.

* An sHR < 1 indicates a protective effect of systemic therapy. RC = Radical Cystectomy; sHR = Subdistribution Hazard Ratio.