Patients with Muscle-Invasive Bladder Cancer with Nonluminal Subtype Derive Greatest Benefit from Platinum Based Neoadjuvant Chemotherapy
Patients with Muscle-Invasive Bladder Cancer with Nonluminal Subtype Derive Greatest Benefit from Platinum Based Neoadjuvant Chemotherapy
复制标题
DOI：
10.1097/ju.0000000000002261
复制
发表时间：
2022-03-01
影响因子：
6.6
通讯作者：
Boormans, Joost L.
中科院分区：
文献类型：
--
作者：
Lotan, Yair;de Jong, Joep J.;Boormans, Joost L.
目的：非转移性肌层浸润性膀胱癌（MIBC）患者在根治性化疗（RC）前进行新辅助化疗（NAC）可获得5%-10%的绝对生存获益。有证据表明，肿瘤之间的分子差异可能会影响对治疗的反应，强调需要临床验证的生物标志物来预测对NAC.Materials和Methods的反应：包括四个膀胱癌队列。使用逆概率加权使NAC给药组和未给药组之间的基线特征（年龄、性别和临床肿瘤分期）更具可比性。使用商业基因组亚型分类器确定分子亚型。使用加权Kaplan-Meier曲线估计生存率。考克斯比例风险模型被用来评估的主要和次要研究终点的总生存期（OS）和癌症特异性survivals.Results：共601例MIBC，其中247人已与NAC和RC治疗，和354接受RC没有NAC。对于NAC，3年OS和癌症特异性生存率的总体净获益分别为7%和5%。在控制了临床病理学变量后，NAC对非管腔性肿瘤的获益最大，3年OS增加10（71%对61%），而管腔肿瘤的获益甚微（63% vs 65%）NAC vs非NAC。在MIBC患者中，一种市售的分子亚型分析显示，NAC对非管腔肿瘤的获益最大，而患有腔肿瘤的患者经历了最小的存活益处。基因组分类器可以帮助识别MIBC患者，他们将从NAC中获益最多。
Purpose: Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) in patients with nonmetastatic muscle-invasive bladder cancer (MIBC) confers an absolute survival benefit of 5%-10%. There is evidence that molecular differences between tumors may impact response to therapy, highlighting a need for clinically validated biomarkers to predict response to NAC.Materials and Methods: Four bladder cancer cohorts were included. Inverse probability weighting was used to make baseline characteristics (age, sex and clinical tumor stage) between NAC-treated and untreated groups more comparable. Molecular subtypes were determined using a commercial genomic subtyping classifier. Survival rates were estimated using weighted Kaplan-Meier curves. Cox proportional hazards models were used to evaluate the primary and secondary study end points of overall survival (OS) and cancer-specific survival, respectively.Results: A total of 601 patients with MIBC were included, of whom 247 had been treated with NAC and RC, and 354 underwent RC without NAC. With NAC, the overall net benefit to OS and cancer-specific survival at 3 years was 7% and 5%, respectively. After controlling for clinicopathological variables, nonluminal tumors had greatest benefit from NAC, with 10% greater OS at 3 years (71% vs 61%), while luminal tumors had minimal benefit (63% vs 65%) for NAC vs non-NAC.Conclusions: In patients with MIBC, a commercially available molecular subtyping assay revealed nonluminal tumors received the greatest benefit from NAC, while patients with luminal tumors experienced a minimal survival benefit. A genomic classifier may help identify patients with MIBC who would benefit most from NAC.