肿瘤降期作为评估新辅助全身治疗在肌层浸润性膀胱癌患者中活性的中间终点。
Tumor downstaging as an intermediate endpoint to assess the activity of neoadjuvant systemic therapy in patients with muscle-invasive bladder cancer.
机构信息
Department of Urology, Icahn School of Medicine at Mount Sinai, New York, New York.
Institute for Healthcare Delivery Science, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.
出版信息
Cancer. 2019 Sep 15;125(18):3155-3163. doi: 10.1002/cncr.32169. Epub 2019 May 31.
BACKGROUND
Achieving a pathologic complete response (pCR) with neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC) has been associated with improved overall survival (OS). This study was aimed at evaluating the impact of pathologic downstaging (pDS; ie, a pT stage at least 1 stage lower than the pre-NAC cT stage) on the OS of patients with MIBC treated with NAC.
METHODS
The Retrospective International Study of Cancers of the Urothelial Tract (RISC) and the National Cancer Database (NCDB) were queried for cT2-4N0M0 patients treated with NAC. A multivariable Cox model including either pDS or pCR was generated. A nested model was built to evaluate the added value of pDS (excluding patients achieving a pCR) to a model including pCR alone. C indices were computed to assess discrimination. NCDB was used for validation. The treatment effect of NAC versus cystectomy alone in achieving pDS was estimated through an inverse probability-weighted regression adjustment.
RESULTS
Overall, 189 and 2010 patients from the RISC and NCDB cohorts, respectively, were included; pDS and pCR were achieved by 33% and 35% and by 20% and 15% in RISC and NCDB, respectively. In both data sets, pDS and pCR were associated with better OS and C indices. Adding pDS excluding pCR to the model with pCR fit the data better (likelihood ratio, P = .019 for RISC and P < .001 for NCDB), and it yielded better discrimination (incremental C index, 4.2 for RISC and 1.6 for NCDB). The treatment effect of NAC in achieving pDS was 2.07-fold (P < .001) in comparison with cystectomy alone.
CONCLUSIONS
A decrease of at least 1 stage from the cT stage to the pT stage is associated with improved OS in patients with MIBC treated with NAC.
背景
新辅助化疗（NAC）治疗肌层浸润性膀胱癌（MIBC）患者获得病理完全缓解（pCR）与总生存（OS）改善相关。本研究旨在评估病理降期（pDS；即比新辅助化疗前 cT 分期至少低 1 期的 pT 分期）对接受 NAC 治疗的 MIBC 患者 OS 的影响。
方法
检索回顾性国际尿路上皮癌研究（RISC）和国家癌症数据库（NCDB）中接受 NAC 治疗的 cT2-4N0M0 患者。生成包含 pDS 或 pCR 的多变量 Cox 模型。构建嵌套模型，以评估排除获得 pCR 的患者后的 pDS 的附加价值（仅包含 pCR）。计算 C 指数以评估判别能力。使用 NCDB 进行验证。通过逆概率加权回归调整估计 NAC 与单纯膀胱切除术在实现 pDS 方面的治疗效果。
结果
RISC 和 NCDB 队列分别纳入 189 例和 2010 例患者；pDS 和 pCR 的实现率分别为 33%和 35%，以及 20%和 15%，RISC 和 NCDB 中。在两个数据集，pDS 和 pCR 均与更好的 OS 和 C 指数相关。将排除 pCR 的 pDS 添加到包含 pCR 的模型中更符合数据（似然比，RISC 为 P=0.019，NCDB 为 P<.001），且具有更好的判别能力（增量 C 指数，RISC 为 4.2，NCDB 为 1.6）。与单纯膀胱切除术相比，NAC 实现 pDS 的治疗效果是其 2.07 倍（P<.001）。
结论
在接受 NAC 治疗的 MIBC 患者中，cT 分期到 pT 分期至少降低 1 期与 OS 改善相关。
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