Neoadjuvant Chemotherapy for High-risk Localized Upper Tract Urothelial Carcinoma: Final Long-term Outcomes from a Phase 2 Clinical Trial and an Expanded Cohort.

We previously reported results from a prospective, multicenter, phase 2 trial that demonstrated a pathologic response rate (<ypT2N0) of 63% among 57 patients with high-risk nonmetastatic upper tract urothelial carcinoma (UTUC) treated with four cycles of neoadjuvant chemotherapy (NAC) comprising gemcitabine and split-dose cisplatin. Here we report updated long-term oncologic outcomes. Outcomes included disease-free survival (DFS, non-urothelial recurrence or death from UTUC), cancer-specific survival (CSS), overall survival (OS), and bladder recurrence-free survival (B-RFS), stratified by pathologic response to NAC in the trial cohort alone (primary analysis) and in an expanded cohort including 69 additional patients (total n = 126) with high-risk nonmetastatic UTUC who received NAC followed by definitive surgery at our institution (secondary analysis). Median follow-up among surviving trial patients was 5.4 yr (interquartile range 4.6-7.5), during which 20 DFS, 11 CSS, and 18 OS events occurred. Estimated 7-yr survival rates were 60% for DFS, 77% for CSS, and 72% for OS. Responders to NAC experienced superior 7-yr DFS (78% vs 31%; log-rank p < 0.001), CSS (90% vs 56%; log-rank p = 0.002), and OS (87% vs 48%; log-rank p < 0.001). Findings were similar in the expanded cohort of 126 patients treated with NAC. B-RFS was not associated with response to NAC. These data support incorporation of NAC in the treatment paradigm for high-risk nonmetastatic UTUC.