Teplitsky Seth L, Cranford Will, Kim Joon Kyung, Bell Spencer, Strup Sydney, Allison Derek, Buchanan Amanda, Myint Zin, Strup Stephen E, Martin Frances, Sood Akshay, Kamat Ashish M, McLouth Christopher J, Hensley Patrick J
Department of Urology, University of Kentucky College of Medicine, Lexington, KY.
Department of Biostatistics, University of Kentucky College of Medicine, Lexington, KY.
Urol Oncol. 2025 Sep;43(9):521.e19-521.e27. doi: 10.1016/j.urolonc.2025.04.010. Epub 2025 May 23.
Patients with histologic subtypes (HS) of urothelial cancers are often excluded from neoadjuvant chemotherapy (NAC) trials for muscle-invasive bladder cancer (MIBC). Additionally, there exist conflicting data regarding the inherent chemotherapeutic sensitivity of individual HS. Herein, we assess the prognostic significance of pathologic response to NAC, a common surrogate endpoint of success in NAC trials, in patients with HS versus pure urothelial carcinoma (PUC).
The National Cancer Database (NCDB) was queried for patients with cT2-4N0M0 MIBC who received NAC and radical cystectomy (RC) between 2004 and 2020. Pathologic response to NAC was defined as complete (ypT0N0), partial (<ypT2N0), and no response (≥ypT2 or ypN+). Kaplan-Meier analysis and log-rank tests were performed for overall survival (OS) and Cox proportional hazard regressions were performed to test relationships between NAC response and the presence of a HS in predicting OS.
5,372 patients were included, with 345 (6.4%) having HS. Nonresponse rates to NAC in HS patients were significantly higher than those with PUC (65.2% vs. 55.8%, P = 0.003). Patients with squamous and glandular differentiation exhibited the highest rates of nonresponse (79% and 72.2%, respectively). In unstratified analysis, patients with HS exhibited shorter OS (P < 0.0001). Patients with HS had uniformly worse OS even after controlling for pathologic response (P = 0.013), with the most notable discrepancy in partial responders (HR = 4.88, 95% CI 2.29-10.38, P < 0.001; 3-year OS 91% vs. 66% for partial response in PUC vs. HS, respectively).
Patients with HS MIBC exhibit poor survival when treated with NAC followed by RC compared with PUC, even when controlling for pathologic response. These data suggest that pathologic response is a less accurate surrogate endpoint in patients with HS relative to PUC, and may suggest a role for therapeutic intensification in the adjuvant setting for patients with HS.
尿路上皮癌组织学亚型（HS）患者通常被排除在肌层浸润性膀胱癌（MIBC）的新辅助化疗（NAC）试验之外。此外，关于各个HS内在化疗敏感性的数据存在冲突。在此，我们评估了NAC病理反应（NAC试验成功的常见替代终点）对HS患者与纯尿路上皮癌（PUC）患者的预后意义。
查询国家癌症数据库（NCDB）中2004年至2020年间接受NAC和根治性膀胱切除术（RC）的cT2-4N0M0 MIBC患者。NAC的病理反应定义为完全缓解（ypT0N0）、部分缓解（<ypT2N0）和无缓解（≥ypT2或ypN+）。进行Kaplan-Meier分析和对数秩检验以评估总生存期（OS），并进行Cox比例风险回归以检验NAC反应与HS的存在之间在预测OS方面的关系。
共纳入5372例患者，其中345例（6.4%）患有HS。HS患者对NAC的无反应率显著高于PUC患者（65.2%对55.8%，P = 0.003）。鳞状和腺性分化患者的无反应率最高（分别为79%和72.2%）。在未分层分析中，HS患者的OS较短（P < 0.0001）。即使在控制病理反应后，HS患者的OS仍普遍较差（P = 0.013），部分缓解者之间的差异最为显著（HR = 4.88，95% CI 2.29-10.38，P < 0.001；PUC与HS部分缓解者的3年OS分别为91%和66%）。
与PUC相比，HS MIBC患者在接受NAC后再行RC治疗时生存率较差，即使在控制病理反应的情况下也是如此。这些数据表明，相对于PUC患者，病理反应在HS患者中作为替代终点的准确性较低，这可能提示在辅助治疗中对HS患者进行强化治疗的作用。
