Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
Urol Oncol. 2020 Jun;38(6):604.e9-604.e17. doi: 10.1016/j.urolonc.2020.02.029. Epub 2020 Apr 3.
Despite immune checkpoint inhibitor (ICI) approval for metastatic renal cell carcinoma (mRCC) in 2015, cytoreductive nephrectomy (CN) is guided by extrapolation from earlier classes of therapy. We evaluated survival outcomes, timing, and safety of combining CN with modern immunotherapy (IO) for mRCC.
From 96,329 renal cancer cases reported to the NCDB between 2015 and 2016, we analyzed 391 surgical candidates diagnosed with clear cell mRCC treated with IO ± CN and no other systemic therapies. Primary outcome was overall survival (OS) stratified by the performance of CN (CN + IO vs. IO alone). Secondary outcomes included OS stratified by the timing of CN, pathologic findings, and perioperative outcomes.
Of 391 patients, 221 (56.5%) received CN + IO and 170 (43.5%) received IO only. Across a median follow-up of 14.7 months, patients who underwent CN + IO had superior OS (median NR vs. 11.6 months; hazard ratio 0.23, P < 0.001), which was upheld on multivariable analyses. IO before CN resulted in lower pT stage, grade, tumor size, and lymphovascular invasion rates compared to upfront CN. Two of 20 patients (10%) undergoing CN post-IO achieved complete pathologic response in the primary tumor (pT0). There were no positive surgical margins, 30-day readmissions, or prolonged length of stay in patients undergoing delayed CN.
Using a large, national, registry-based cohort, we provide the first report of survival outcomes in mRCC patients treated with CN combined with modern IO. Our findings support an oncologic role for CN in the ICI era and provide preliminary evidence regarding the timing and safety of CN relative to IO administration.
尽管免疫检查点抑制剂（ICI）于 2015 年被批准用于转移性肾细胞癌（mRCC），但细胞减灭性肾切除术（CN）是基于对早期治疗类别的推断。我们评估了 CN 联合现代免疫疗法（IO）治疗 mRCC 的生存结果、时机和安全性。
我们分析了 2015 年至 2016 年期间向 NCDB 报告的 96329 例肾肿瘤病例中的 391 例手术候选者，这些患者诊断为接受 IO ± CN 治疗且未接受其他全身治疗的透明细胞 mRCC。主要结局是根据 CN 的实施情况（CN + IO 与 IO 单药治疗）分层的总生存期（OS）。次要结局包括根据 CN 的时机、病理发现和围手术期结局分层的 OS。
在 391 例患者中，221 例（56.5%）接受了 CN + IO，170 例（43.5%）接受了 IO 单药治疗。在中位随访 14.7 个月期间，接受 CN + IO 的患者 OS 更优（中位 NR 与 11.6 个月；风险比 0.23，P < 0.001），这在多变量分析中仍然成立。CN 前 IO 导致的 pT 分期、分级、肿瘤大小和血管淋巴管侵犯率低于 CN upfront。20 例接受 CN 后 IO 的患者中有 2 例（10%）在原发肿瘤中获得完全病理缓解（pT0）。CN 术后无阳性切缘，30 天再入院率和住院时间延长。
使用大型的、基于全国范围的注册队列，我们首次报道了接受 CN 联合现代 IO 治疗的 mRCC 患者的生存结果。我们的研究结果支持 CN 在 ICI 时代的肿瘤学作用，并提供了关于 CN 相对于 IO 给药的时机和安全性的初步证据。
