Updated long-term follow-up from a phase II clinical trial of gemcitabine and cisplatin as neoadjuvant chemotherapy for patients with high-grade upper tract urothelial carcinoma.
Authors: Viranda Jayalath, Min Yuen Teo, Melissa Assel, Daniel Rodriguez, Abraham Meyerson, 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, Jonathan E. Rosenberg, Gopa Iyer, Dean F. Bajorin, Jonathan Coleman
Journal: Journal of Clinical Oncology (2025)

811 Background: We previously reported our multicenter phase II trial of neoadjuvant gemcitabine and split-dose cisplatin (GC) in 57 patients with high-grade upper tract urothelial carcinoma (HG UTUC), where 63% of patients experienced a pathological response (&lt;ypT2 N0) at radical nephroureterectomy (RNU). Pathological response was associated with superior progression-free (PFS) and overall survival (OS) over a median 3-years of follow-up. Herein we report survival outcomes among the 50 patients treated at our institution with long-term follow-up. Methods: Patients with histologically confirmed HG UTUC and/or radiographically visible tumor stage T2-T4a N0/NX disease with a positive upper tract urine cytology were eligible. All patients received 4 cycles of split-dose GC followed by RNU and lymphadenectomy. The primary endpoints for this report were PFS (defined as metastasis or death from UTUC), cancer-specific survival (CSS) and OS, stratified by pathological response to NAC. Responders (&lt;ypT2 N0) included both complete responders (CR, ypT0 N0) and partial responders (PR, ypTa/Tis/T1 N0/X); non-responders (NR) included ≥ypT2 Nany. Follow up started at RNU and patients were censored at the last occurrence of: clinical assessment, imaging study, or blood draw. Kaplan-Meier analyses estimated survival outcomes and log-rank tests evaluated for significant differences. Results: Of the 50 patients available for analysis, 32 (64%) were responders, of which 10 (20%) were CR. Baseline characteristics were similar between responders and NR. Forty-four of 50 patients tolerated ≥3 cycles of GC. Over a median follow-up among survivors of 5.7 years (interquartile range: 5.0, 7.9), 16 progression events, 11 cancer-specific deaths, and 16 total deaths occurred. Overall event rates were 63% and 63% for PFS, 77% and 70% for CSS, and 75% and 54% for OS, at 7- and 9-years, respectively. Estimated survival was higher among responders, compared to NR for PFS (log-rank p&lt;0.001), CSS (log-rank p=0.002), and OS (log-rank p=0.002); corresponding 7- and 9-year event rates are presented in the table. Survival and event estimates were similar between CR and PR. Conclusions: These findings demonstrate a durable long-term progression and survival advantage of split-dose GC as NAC for HG UTUC among patients with a pathological response. Clinical trial information: NCT01261728 . 7- and 9-year PFS, CSS, and OS rates in patients treated with NAC, stratified by pathological response at RNU. Outcome Characteristic* 7 Years (95% CI) 9 Years (95% CI) PFS Responders 80% (64%, 99%) 80% (64%, 99%) Non-responders 36% (19%, 69%) 36% (19%, 69%) CSS Responders 89% (76%, 100%) 79% (60%, 100%) Non-responders 54% (33%, 88%) 54% (33%, 88%) OS Responders 87% (73%, 100%) 67% (46%, 99%) Non-responders 54% (33%, 88%) 32% (14%, 77%) *Responders were defined as &lt;ypT2 N0/NX; Non-responders were defined as ≥ypT2 Nany.