肌浸润性膀胱癌患者新辅助化疗后ATM、RB1、ERCC2和FANCC突变与病理完全缓解的相关性分析：SWOG S1314试验结果

Correlative Analysis of ATM, RB1, ERCC2, and FANCC Mutations and Pathologic Complete Response After Neoadjuvant Chemotherapy in Patients with Muscle-invasive Bladder Cancer: Results from the SWOG S1314 Trial

EUROPEAN UROLOGY

影响因子:25.2

分区:医学1区 Top / 泌尿学与肾脏学1区

发表日期:2024 Oct

作者: Elizabeth R Plimack, Catherine Tangen, Melissa Plets, Rutika Kokate, Joanne Xiu, Chadi Nabhan, Eric A Ross, Erin Grundy, Woonyoung Choi, Colin P N Dinney, I-Ling C Lee, Megan Fong, M Scott Lucia, Siamak Daneshmand, Dan Theodorescu, Amir Goldkorn, Seth P Lerner, Thomas W Flaig, David J McConkey

DOI: 10.1016/j.eururo.2024.06.018

摘要

我们之前报道，携带ATM、RB1、FANCC或ERCC2任一基因突变的肿瘤更可能对新辅助顺铂化疗（NAC）产生反应，从而在膀胱切除术时获得无癌的手术标本（pT0）。在本研究中，我们验证了这一发现。利用CARIS 592基因检测面板（Caris Life Sciences，美国菲尼克斯），分析了来自多中心大规模试验（S1314）中105例接受新辅助吉西他滨和顺铂（GC）或高剂量甲氨蝶呤、长春碱、阿霉素和顺铂（DDMVAC）治疗的术前肿瘤标本。结果显示，任何一项基因突变都预测手术时达到pT0（比值比=5.36；95%置信区间[CI]为2.05至14.02；双侧p=0.0006）。该生物标志物在预测是否存在疾病方面优于预测无疾病（pT0的阴性预测值为86%；95%CI为73%至94%），而在预测无疾病方面的正预测值为48%；95%CI为35%至62%。不同治疗组（DDMVAC与GC）与基因变异之间在pT0的预测上没有交互作用。结合临床评估，这些发现有助于指导膀胱保存策略的患者选择，尤其是在接受顺铂化疗后。

Abstract

We previously reported that tumors harboring any one of four gene mutations (ATM, RB1, FANCC, or ERCC2) were likely to respond to neoadjuvant cisplatin-based chemotherapy (NAC), resulting in cancer-free surgical specimens at the time of cystectomy (pT0). Here, we report our validation of this finding. Using the CARIS 592 Gene Panel (Caris Life Sciences, Phoenix, AZ, USA), we analyzed 105 pre-NAC tumor specimens from a large multicenter trial (S1314) of either neoadjuvant gemcitabine and cisplatin (GC), or dose-dense methotrexate, vinblastine, Adriamycin, and cisplatin (DDMVAC). We found that a mutation in any one of these four genes predicted for pT0 at surgery (odds ratio = 5.36; 95% confidence interval [CI] 2.05, 14.02; two-sided p = 0.0006). The biomarker was better at predicting the presence of disease (negative predictive value for pT0 86%; 95% CI 73%, 94%) than the absence of disease (positive predictive value for pT0 48%; 95% CI 35%, 62%). There was no evidence of an interaction between the treatment arm (DDMVAC vs GC) and the genetic variant in terms of pT0. When combined with clinical assessment, these findings help inform patient selection for bladder preservation after cisplatin-based chemotherapy.