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.

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Journal
European Urology
Published
2025-09-27
DOI
https://doi.org/10.1016/j.eururo.2025.08.012
Citations
3
Primary Topic
Bladder and Urothelial Cancer Treatments
Type
article
Field-Weighted Citation Impact
6.02
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article

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

Muhammad A. Rizvi, Hebert Alberto Vargas, Jonathan A. Coleman, Antonio F Muina et al.
3 citations
European Urology
Bladder and Urothelial Cancer Treatments
6.02
article

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

Muhammad A. Rizvi, Hebert Alberto Vargas, Jonathan A. Coleman, Antonio F Muina, Guido Dalbagni, Hikmat A Al‐Ahmadie, Jacob Rosenberg, Timothy F. Donahue, Paul Palyca, Eugene J. Pietzak, S. Machele Donat, Andrea B. Apolo, Melissa J. Assel, Bradley W. Lash, Scot A. Niglio, Soleen Ghafoor, Kwanghee Kim, Viranda H. Jayalath, Abraham Meyerson, Steven J. Shichman, Dean F. Bajorin, Gopa Iyer, A Ari Hakimi, Nicole E. Benfante, K. Eugene, Suresh Nair, Anoop Meraney, Bernard H. Bochner, Angelo A. Baccala, Daniel Rodriguez, Jeffrey M. Kamradt, Harry W. Herr, Scott K. Swanson
article en
3 citations

Abstract

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.

European UrologyVol. 89(2)
Hartford Hospital (US), Lehigh Valley Hospital-Pocono (US), Memorial Sloan Kettering Cancer Center (US), Lehigh Valley Health Network (US), Mayo Clinic in Arizona (US), Miami Heart Research Institute (US), National Cancer Institute (US)
Openalex Percentile: Top 3%
Bladder and Urothelial Cancer Treatments
6.02
DOIOpen Access PDFOpenAlex
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