Systemic Therapy for Muscle-Invasive Urothelial Carcinoma of the Bladder (Muscle-Invasive Bladder Cancer): Insights From Real-World Data.

Abstract

Neoadjuvant cisplatin-based chemotherapy before radical cystectomy (RC) has been standard-of-care treatment for muscle-invasive bladder cancer (MIBC) for over two decades. The study aimed to explore the outcomes of systemic therapy for MIBC. A cohort analysis of patients treated with RC for MIBC across the United States was performed using the National Cancer Database. The primary outcome measure was overall survival (OS), defined as the time from the date of initial diagnosis to the date of death from any cause. Additional variables including patient characteristics, pathologic complete response (pCR), clinical complete response (cCR), surgical margins, and the impact of surgical volume were also explored. Between 2006 and 2021, 47,983 patients who underwent RC for MIBC were included: 14,730 (31%) received neoadjuvant systemic therapy before RC. With a median follow-up of 82 months, the median OS was 61.1 months (95% CI, 59.3 to 62.59). Pathologic T0 and downstaging to ≤pT2 were associated with improved OS. Immunotherapy monotherapy was 55%-66% less likely to induce a pCR but was associated with improved OS compared with multiagent chemotherapy. Treatment at facilities at 90th+ percentile of surgical volume was associated with improved OS. Neoadjuvant systemic therapy was associated with improved OS compared with adjuvant systemic therapy. These results support the use of neoadjuvant systemic therapy and underscore that in addition to pT0, ypTis carcinoma in situ (CIS) and ypT1 are associated with improved OS. Perioperative systemic therapy maybe more effective before rather than after surgery. Future studies should focus on whether patients with no evidence of muscle-invasive disease (<cT2) after neoadjuvant therapy are candidates for bladder-preserving strategies.