The Impact of Relative Dose Intensity on Pathological Complete Response in Neoadjuvant Chemotherapy of Muscle-Invasive Urothelial Cancer: a Multicenter Retrospective Study.

BACKGROUND:Cisplatin-based neoadjuvant chemotherapy (NAC) improves survival in muscle-invasive urothelial cancer (MIUC), yet pathological complete response (pCR) is achieved in a minority of patients. Relative dose intensity (RDI) is a potentially modifiable determinant of chemotherapy efficacy, but its impact during NAC in MIUC remains unexplored. METHODS:This multicenter retrospective study included patients with MIUC treated with cisplatin-gemcitabine NAC followed by radical cystectomy. Relative dose intensity was calculated from original administration records and categorized as ≥85% vs <85%. The primary endpoint was pCR (ypT0N0M0). Secondary endpoints included overall survival (OS) and event-free survival (EFS). RESULTS:A total of 330 patients were included; 66% maintained RDI ≥ 85%. Overall pCR rate was 25.2%. Patients with RDI ≥ 85% achieved higher pCR rates compared with those with RDI < 85% (29.7% vs 16.2%; P = .008). Relative dose intensity  ≥ 85% remained independently associated with pCR in multivariable analysis (odds ratio = 2.10; P = .032). Preserved RDI was also associated with improved EFS (hazard ratio [HR] = 0.65; P = .039) and OS (HR = 0.53; P = .026) at univariate analysis. Achievement of pCR was strongly associated with superior EFS (HR = 0.23; P < .001) and OS (HR = 0.35; P = .009). CONCLUSION:Preservation of cisplatin RDI ≥ 85% during NAC is independently correlated with higher pCR rates and associated to a better survival trend in MIUC. Optimization of chemotherapy delivery represents a clinically actionable strategy to enhance neoadjuvant efficacy.