University of Colorado, School of Medicine, Aurora, Colorado.
Fred Hutchinson Cancer Research Center, Seattle, Washington.
Clin Cancer Res. 2021 May 1;27(9):2435-2441. doi: 10.1158/1078-0432.CCR-20-2409. Epub 2021 Feb 10.
Dose-dense methotrexate-vinblastine-adriamycin-cisplatin (ddMVAC) and gemcitabine-cisplatin (GC) are accepted neoadjuvant regimens for muscle-invasive bladder cancer. The aim of this study was to validate the score from a coexpression extrapolation (COXEN) algorithm-generated gene expression model (GEM) as a biomarker in patients undergoing radical cystectomy.
Eligibility included cT2-T4a N0 M0, urothelial bladder cancer, ≥ 5 mm of viable tumor, cisplatin eligible, with plan for cystectomy; 237 patients were randomized between ddMVAC, given every 14 days for four cycles, and GC, given every 21 days for four cycles. The primary objective assessed prespecified dichotomous treatment-specific COXEN score as predictive of pT0 rate or ≤ pT1 (downstaging) at surgery.
Among 167 evaluable patients, the OR for pT0 with the GC GEM score in GC-treated patients was 2.63 [ = 0.10; 95% confidence interval (CI), 0.82-8.36]; for the ddMVAC COXEN GEM score with ddMVAC treatment, the OR was 1.12 ( = 0.82, 95% CI, 0.42-2.95). The GC GEM score was applied to pooled arms (GC and ddMVAC) for downstaging with an OR of 2.33 ( = 0.02; 95% CI, 1.11-4.89). In an intention-to-treat analysis of eligible patients ( = 227), pT0 rates for ddMVAC and GC were 28% and 30% ( = 0.75); downstaging was 47% and 40% ( = 0.27), respectively.
Treatment-specific COXEN scores were not significantly predictive for response to individual chemotherapy treatment. The COXEN GEM GC score was significantly associated with downstaging in the pooled arms. Additional biomarker development is planned.
密集剂量甲氨蝶呤-长春碱-阿霉素-顺铂（ddMVAC）和吉西他滨-顺铂（GC）是肌层浸润性膀胱癌的可接受的新辅助治疗方案。本研究的目的是验证来自共表达外推（COXEN）算法生成的基因表达模型（GEM）的评分作为接受根治性膀胱切除术患者的生物标志物。
入选标准包括 cT2-T4a N0 M0、尿路上皮膀胱癌、≥5mm 的存活肿瘤、顺铂适用且计划行膀胱切除术；237 例患者随机分为 ddMVAC 组，每 14 天给予 4 个周期，GC 组，每 21 天给予 4 个周期。主要评估指标是预测手术时 pT0 率或≤pT1（降期）的预设二分类治疗特异性 COXEN 评分。
在 167 例可评估患者中，GC 治疗患者的 GC GEM 评分与 pT0 的比值比（OR）为 2.63[=0.10；95%置信区间（CI），0.82-8.36]；ddMVAC 治疗患者的 ddMVAC COXEN GEM 评分的 OR 为 1.12[=0.82，95%CI，0.42-2.95]。GC GEM 评分应用于联合治疗组（GC 和 ddMVAC）的降期 OR 为 2.33[=0.02；95%CI，1.11-4.89]。在 227 例符合条件患者的意向治疗分析中，ddMVAC 和 GC 的 pT0 率分别为 28%和 30%[=0.75]；降期率分别为 47%和 40%[=0.27]。
治疗特异性 COXEN 评分对个体化疗治疗的反应没有显著预测作用。COXEN GEM GC 评分与联合治疗组的降期显著相关。计划进一步开发生物标志物。
