肌层浸润性膀胱癌新辅助化疗的 2 期研究的长期结果（SWOG S1314；NCT02177695）。
Long-term Outcomes from a Phase 2 Study of Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer (SWOG S1314; NCT02177695).
机构信息
School of Medicine, University of Colorado, Aurora, CO, USA.
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
出版信息
Eur Urol. 2023 Sep;84(3):341-347. doi: 10.1016/j.eururo.2023.06.014. Epub 2023 Jul 4.
BACKGROUND
The COXEN gene expression model was evaluated for prediction of response to neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC).
OBJECTIVE
To conduct a secondary analysis of the association of each COXEN score with event-free survival (EFS) and overall survival (OS) and by treatment arm.
DESIGN, SETTING, AND PARTICIPANTS: This was a randomized phase 2 trial of neoadjuvant gemcitabine-cisplatin (GC) or dose-dense methotrexate-vinblastine-adriamycin-cisplatin (ddMVAC) in MIBC.
INTERVENTION
Patients were randomized to ddMVAC (every 14 d) or GC (every 21 d), both for four cycles.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
EFS events were defined as progression or death before scheduled surgery, a decision to not undergo surgery, recurrence, or death due to any cause after surgery. Cox regression was used to evaluate the COXEN score or treatment arm association with EFS and OS.
RESULTS AND LIMITATIONS
A total of 167 evaluable patients were included in the COXEN analysis. The COXEN scores were not significantly prognostic for OS or EFS in the respective arms, but the GC COXEN score had a hazard ratio (HR) of 0.45 (95% confidence interval [CI] 0.20-0.99; p = 0.047) when the arms were pooled. In the intent-to-treat analysis (n = 227), there was no significant difference between ddMVAC and GC for OS (HR 0.87, 95% CI 0.54-1.40; p = 0.57) or EFS (HR 0.86, 95% CI 0.59-1.26; p = 0.45). Among the 192 patients who underwent surgery, pathologic response (pT0 vs downstaging vs no response) was strongly correlated with superior postsurgical survival (5-yr OS 90%, 89% and 52%, respectively).
CONCLUSIONS
The COXEN GC score has prognostic value for patients receiving cisplatin-based neoadjuvant treatment. The randomized, prospective design provides estimates of OS and EFS for GC and ddMVAC in this population. Pathologic response (<pT2) performed well as an intermediate endpoint in this modern cohort. For expediency in evaluating new regimens, pathologic response should continue to be used in phase 2 trials.
PATIENT SUMMARY
In this study, we evaluated a biomarker to predict the response to chemotherapy. The results did not meet the preset study parameters, but our study provides information on clinical outcomes with the use of chemotherapy before surgery for bladder cancer.
背景
COXEN 基因表达模型已被评估用于预测肌层浸润性膀胱癌（MIBC）新辅助化疗的反应。
目的
对 COXEN 评分与无事件生存（EFS）和总生存（OS）以及与治疗臂的相关性进行二次分析。
设计、设置和参与者：这是一项 MIBC 新辅助吉西他滨联合顺铂（GC）或密集剂量甲氨蝶呤联合长春碱-阿霉素-顺铂（ddMVAC）的随机 2 期试验。
干预
患者被随机分配到 ddMVAC（每 14 天）或 GC（每 21 天），均为 4 个周期。
结局测量和统计分析
EFS 事件定义为计划手术前进展或死亡、决定不进行手术、手术后复发或任何原因导致的死亡。使用 Cox 回归评估 COXEN 评分或治疗臂与 EFS 和 OS 的相关性。
结果和局限性
共有 167 名可评估患者纳入 COXEN 分析。在各自的臂中，COXEN 评分与 OS 或 EFS 均无显著预后意义，但当臂合并时，GC COXEN 评分的危险比（HR）为 0.45（95%置信区间 [CI] 0.20-0.99；p=0.047）。在意向治疗分析（n=227）中，ddMVAC 和 GC 在 OS（HR 0.87，95%CI 0.54-1.40；p=0.57）或 EFS（HR 0.86，95%CI 0.59-1.26；p=0.45）方面无显著差异。在 192 名接受手术的患者中，病理反应（pT0 与降期与无反应）与术后生存的改善密切相关（5 年 OS 分别为 90%、89%和 52%）。
结论
COXEN GC 评分对接受顺铂为基础的新辅助治疗的患者具有预后价值。这项随机、前瞻性设计提供了 GC 和 ddMVAC 在该人群中的 OS 和 EFS 的估计值。在这个现代队列中，病理反应（<pT2）作为中间终点表现良好。为了评估新方案的便利性，病理反应应继续在 2 期试验中使用。
患者总结
在这项研究中，我们评估了一种生物标志物来预测化疗的反应。结果未达到预设的研究参数，但我们的研究提供了在膀胱癌术前使用化疗的临床结果信息。
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