Department of Urology, Icahn School of Medicine at Mount Sinai, NY; Department of Urology, Vita-Salute San Raffaele University, Milan, Italy.
Department of Urology, Icahn School of Medicine at Mount Sinai, NY.
Urol Oncol. 2020 Aug;38(8):684.e9-684.e15. doi: 10.1016/j.urolonc.2020.03.008. Epub 2020 Apr 10.
Presently, no level I evidence is available to support the use of neoadjuvant chemotherapy (N)(AC) in patients diagnosed with high-grade upper tract urothelial carcinoma (UTUC). We aimed to compare outcomes of patients treated with radical nephroureterectomy (RNU) who received NAC vs. those who received AC.
The National Cancer Database was queried for UTUC patients with cT2-4N0M0 disease treated with RNU and NAC or AC. The role of NAC or AC on overall survival (OS) was evaluated by means of a multivariable Cox regression. Time to death was evaluated from diagnosis.
Overall, 936 patients were identified, 128 (14%) received NAC whereas 808 (86%) received AC. No difference was observed between NAC vs. AC in terms of OS (P = 0.9). When sub-stratifying patients who received NAC in responders (cT>pT, given pN0; n = 46 [36%]) vs. nonresponders (n = 82 [64%]), we found that, relatively to AC, the subgroup of patients who did not respond to NAC had higher risk of dying from any cause (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.03,1.91; P = 0.03), whereas the sub-group who responded to NAC had better OS (HR: 0.45; 95% CI: 0.24,0.85; P = 0.01). The 5-year OS rates for responders to NAC vs. nonresponders vs. AC were: 71% vs. 26% vs. 43%, respectively. A landmark analysis fitted at 6 months after diagnosis, including 903 patients (NAC: 126 vs. AC: 777) confirmed our findings.
while we found no difference in outcomes between NAC vs. AC in high-grade UTUC, we found a hypothesis-generating association between survival and response to NAC. Further studies aimed at identifying potential responders to NAC are warranted.
目前，尚无一级证据支持对诊断为高级别上尿路上皮癌（UTUC）的患者使用新辅助化疗（N）（AC）。我们旨在比较接受根治性肾输尿管切除术（RNU）治疗的患者接受 NAC 与接受 AC 的患者的结局。
国家癌症数据库中对接受 RNU 治疗且患有 cT2-4N0M0 疾病的 UTUC 患者进行了查询，这些患者接受了 NAC 或 AC。通过多变量 Cox 回归评估 NAC 或 AC 对总生存（OS）的作用。从诊断开始评估死亡时间。
共有 936 名患者被确定，其中 128 名（14%）接受了 NAC，而 808 名（86%）接受了 AC。在 OS 方面，NAC 与 AC 之间无差异（P=0.9）。当在接受 NAC 的患者中根据应答情况进行分层（cT>pT，给予 pN0；n=46[36%]）和无应答者（n=82[64%]）时，我们发现，与 AC 相比，未对 NAC 产生应答的患者死亡风险更高（风险比[HR]：1.41；95%置信区间[CI]：1.03，1.91；P=0.03），而对 NAC 产生应答的患者 OS 更好（HR：0.45；95% CI：0.24，0.85；P=0.01）。对 NAC 产生应答的患者的 5 年 OS 率与无应答者和 AC 分别为：71%、26%和 43%。在诊断后 6 个月进行的里程碑分析（纳入 903 名患者（NAC：126 名，AC：777 名））证实了我们的发现。
虽然我们在高级别 UTUC 中未发现 NAC 与 AC 之间的结局差异，但我们发现了生存与对 NAC 反应之间存在假说生成的关联。需要进一步研究以确定潜在的 NAC 应答者。
