Martini Alberto, Daza Jorge, Poltiyelova Elona, Gul Zeynep, Heard John R, Ferket Bart S, Waingankar Nikhil, Galsky Matthew D, Sfakianos John P
Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Institute for Healthcare Delivery Science, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
BJU Int. 2019 Oct;124(4):665-671. doi: 10.1111/bju.14719. Epub 2019 Mar 26.
To evaluate whether pathological downstaging (pDS) was more informative in predicting overall survival (OS) than pathological complete response (pCR) in patients treated with neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC).
The National Cancer Database was queried for patients with high-grade cN0M0 disease who had received NAC. pDS was defined as a decrease of at least one stage from cT to pT stage along with pN0, including pCR. A multivariable Cox model predicting OS was generated by fitting alternatively either pDS or pCR, and adjusted for potential confounders. The discrimination of the Cox models for predicting OS was evaluated using Harrell's C-index. The analyses were repeated in patients diagnosed as having cT2-4N0M0 disease.
Among 264 patients meeting the inclusion criteria, 72 (27%) and 39 (15%) achieved pDS and pCR, respectively. On multivariable analysis, both pDS (hazard ratio [HR] 0.24, 95% confidence interval [CI] 0.13, 0.45; P < 0.001) and pCR (HR 0.37, 95% CI 0.18, 0.79; P = 0.01) were associated with OS. The model including pDS achieved better discrimination with respect to the model including pCR: C-index 76.4 vs 72.7, respectively. In the 128 patients diagnosed with cT2-4 disease, both pDS (HR 0.19, 95% CI 0.09, 0.40; P < 0.001) and pCR (HR 0.31, 95% CI 0.11, 0.85; P = 0.023) were confirmed as predictors of OS. The model including pDS was confirmed to discriminate better than the model including pCR: C-index 75 vs 68.9, respectively.
The study showed that pDS after NAC for UTUC was more informative than pCR when predicting OS. These findings, although requiring prospective validation, can aid in the design of clinical trials seeking to refine the use of chemotherapy and other systemic therapies in this setting.
评估在接受新辅助化疗（NAC）的上尿路尿路上皮癌（UTUC）患者中，病理降期（pDS）在预测总生存期（OS）方面是否比病理完全缓解（pCR）更具信息价值。
查询国家癌症数据库中接受NAC治疗的高级别cN0M0疾病患者。pDS定义为从cT期到pT期至少下降一个分期且pN0，包括pCR。通过交替拟合pDS或pCR生成预测OS的多变量Cox模型，并对潜在混杂因素进行校正。使用Harrell's C指数评估Cox模型预测OS的辨别力。在诊断为cT2-4N0M0疾病的患者中重复进行分析。
在264例符合纳入标准的患者中，分别有72例（27%）和39例（15%）达到pDS和pCR。多变量分析显示，pDS（风险比[HR]0.24，95%置信区间[CI]0.13，0.45；P<0.001）和pCR（HR 0.37，95%CI 0.18，0.79；P = 0.01）均与OS相关。包含pDS的模型在辨别力方面优于包含pCR的模型：C指数分别为76.4和72.7。在128例诊断为cT2-4疾病的患者中，pDS（HR 0.19，95%CI 0.09，0.40；P<0.001）和pCR（HR 0.31，95%CI 0.11，0.85；P = 0.023）均被确认为OS的预测因素。包含pDS的模型被证实比包含pCR的模型辨别力更好：C指数分别为75和68.9。
该研究表明，对于UTUC患者，NAC后的pDS在预测OS方面比pCR更具信息价值。这些发现尽管需要前瞻性验证，但有助于设计旨在优化该情况下化疗和其他全身治疗应用的临床试验。
