Neoadjuvant Chemotherapy for High-risk Localized Upper Tract Urothelial Carcinoma: Final Long-term Outcomes from a Phase 2 Clinical Trial and an Expanded Cohort
Viranda H. Jayalath, Melissa Assel, Gopa Iyer, Scot A. Niglio, Bernard H. Bochner, Guido Dalbagni, S. Machele Donat, Harry W. Herr, Eugene K. Cha, Timothy F. Donahue, Eugene J. Pietzak, A Ari Hakimi, Kwanghee Kim, Hikmat Al‐Ahmadie, Hebert Alberto Vargas, Soleen Ghafoor, Nicole Benfante, Daniel Rodriguez, Abraham Meyerson, Anoop Meraney, Steven J. Shichman, Jeffrey M. Kamradt, Suresh Nair, Angelo A. Baccala, Paul Palyca, Bradley W. Lash, Muhammad A. Rizvi, Scott K. Swanson, Antonio F Muina, Andrea B. Apolo, Jonathan E. Rosenberg, Dean F. Bajorin, Jonathan A. Coleman
Abstract
In a prospective phase 2 trial in patients with high-risk nonmetastatic upper tract urothelial carcinoma, cisplatin-based neoadjuvant chemotherapy (NAC) resulted in durable 7-yr oncologic outcomes. The response to NAC was highly predictive of survival. These findings were confirmed in 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.