Efficacy of cisplatin-based neoadjuvant chemotherapy and risk factors for residual extravesical disease in muscle-invasive bladder cancer: insights from a nationwide cohort.

Background: Cisplatin-based neoadjuvant chemotherapy (NAC) improves survival in muscle-invasive bladder cancer (MIBC) as long as disease progression does not occur during treatment. However, predictors of NAC sensitivity remain elusive in clinical practice. This study evaluated the efficacy of NAC followed by radical cystectomy (NAC-RC) in cStage II-IIIA MIBC and identified the risk factors associated with residual extravesical disease.

Methods: Clinical data from 1474 patients who underwent radical cystectomy for cStage II-IIIA urothelial carcinoma were collected from 36 institutions of the Japanese Urological Oncology Group. Overall survival (OS) and non-urinary tract recurrence-free survival (NUT-RFS) were compared between the NAC-RC and upfront RC groups using the Kaplan-Meier method adjusted by inverse probability of treatment weighting. Logistic regression was used to identify independent risk factors for RED.

Results: Pathological complete response (pT0N0) was achieved in 33.1 and 20.2% of cStage II and IIIA patients in the NAC-RC group, respectively, compared with 16.3 and 4.5% in the RC group. NAC significantly improved the OS and NUT-RFS in the IPTW-adjusted cohort. BCG-unresponsiveness, low serum albumin levels, and a high neutrophil-to-lymphocyte ratio were independent predictors of RED in the NAC-RC cohort. Squamous differentiation was associated with worse prognosis but a favorable response to NAC in some tumors.

Conclusions: Cisplatin-based NAC improves outcomes in patients with cStage II-IIIA MIBC, including some tumors with squamous differentiation; however, its benefits may be limited in BCG-unresponsive cases. Given the biological heterogeneity of urothelial cancer, individualized treatment planning that integrates biological features and treatment history is needed for patients with MIBC.