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

IF 25.2 1区医学 Q1 UROLOGY & NEPHROLOGY

European urology Pub Date : 2025-09-25 DOI:10.1016/j.eururo.2025.08.012

Viranda H. Jayalath, Melissa Assel, Gopa Iyer, Scot 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 A. Al-Ahmadie, H. Alberto Vargas, Soleen Ghafoor, Nicole E. Benfante, Daniel V. Rodriguez, Abraham R. Meyerson, Anoop M. Meraney, Jonathan A. Coleman

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引用次数: 0

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.

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高风险局限性上尿路上皮癌的新辅助化疗：来自2期临床试验和扩大队列的最终长期结果

我们之前报道了一项前瞻性、多中心、2期试验的结果，该试验显示，在57名高风险非转移性上尿路上皮癌（UTUC）患者中，接受吉西他滨和分剂量顺铂组成的4个周期新辅助化疗（NAC）治疗的患者中，病理缓解率（<ypT2N0）为63%。在此，我们报告最新的长期肿瘤预后。结果包括无病生存期（DFS，非尿路上皮复发或死于UTUC），癌症特异性生存期（CSS），总生存期（OS）和膀胱无复发生存期（B-RFS），根据NAC的病理反应进行分层，单独试验队列（主要分析）和扩大队列，包括69例额外的高风险非转移性UTUC患者（总n = 126），这些患者接受NAC后在我们机构进行最终手术（次要分析）。存活的试验患者的中位随访时间为5.4年（四分位数范围4.6-7.5），期间发生了20例DFS， 11例CSS和18例OS事件。估计DFS的7年生存率为60%，CSS为77%，OS为72%。NAC应答者的7年DFS （78% vs 31%; log-rank p < 0.001）、CSS （90% vs 56%; log-rank p = 0.002）和OS （87% vs 48%; log-rank p < 0.001）均优于NAC应答者。在126例接受NAC治疗的扩大队列中，结果相似。B-RFS与NAC疗效无相关性。这些数据支持将NAC纳入高风险非转移性UTUC的治疗模式。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European urology 医学-泌尿学与肾脏学

CiteScore

43.00

自引率

2.60%

发文量

1753

审稿时长

23 days

期刊介绍： European Urology is a peer-reviewed journal that publishes original articles and reviews on a broad spectrum of urological issues. Covering topics such as oncology, impotence, infertility, pediatrics, lithiasis and endourology, the journal also highlights recent advances in techniques, instrumentation, surgery, and pediatric urology. This comprehensive approach provides readers with an in-depth guide to international developments in urology.