Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida.
Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center, Tampa, Florida.
JAMA Netw Open. 2022 May 2;5(5):e2212347. doi: 10.1001/jamanetworkopen.2022.12347.
Level I evidence has failed to demonstrate an overall survival (OS) advantage for cytoreductive nephrectomy in patients with metastatic clear cell renal cell carcinoma (ccRCC) in the modern era, which is at odds with observational studies reporting a marked OS benefit associated with these operations. These observational studies were not designed to adjust for unmeasured confounding.
To assess whether cytoreductive nephrectomy is associated with improved OS in patients with metastatic ccRCC.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study identified patients with metastatic ccRCC in the National Cancer Database from January 1, 2006, to December 31, 2016, who received systemic targeted therapy. The analysis was finalized on July 23, 2021.
Receipt of cytoreductive nephrectomy.
The primary outcome was OS from the date of diagnosis to death or censoring at last follow-up. Distance from the patients' zip code of residence to the treating facility was identified as a valid instrument and was used in a 2-stage residual inclusion instrumental variable analysis. Conventional adjustments for selection bias, multivariable Cox proportional hazards regression, and propensity score matching were performed for comparison. Measured covariates adjusted for in all analyses included age, sex, race, Charlson-Deyo score, facility type, year of diagnosis, clinical T stage, and clinical N stage.
The final study population included 12 766 patients (median age, 63 years; IQR, 56-70 years; 8744 [68%] male; 11 206 [88%] White). Cytoreductive nephrectomy was performed in 5005 patients (39%). Conventional adjustments for selection bias demonstrated a significant OS benefit associated with cytoreductive nephrectomy (multivariable Cox proportional hazards regression: hazard ratio [HR], 0.49; 95% CI, 0.47-0.51; propensity score matching: HR, 0.48; 95% CI, 0.46-0.50). Instrumental variable estimates did not demonstrate an association between cytoreductive nephrectomy and OS (HR, 0.92; 95% CI, 0.78-1.09).
Instrumental variable analysis did not demonstrate a survival advantage associated with cytoreductive nephrectomy for patients with metastatic ccRCC. This discrepancy likely reflects the fact that surgical indication for cytoreductive nephrectomy is primarily driven by factors that are not commonly measured or available in observational data sets.
一级证据未能证明在现代，细胞减灭性肾切除术对转移性透明细胞肾细胞癌（ccRCC）患者的总生存（OS）有优势，这与报告这些手术与明显 OS 获益相关的观察性研究相矛盾。这些观察性研究并非旨在调整未测量的混杂因素。
评估细胞减灭性肾切除术是否与转移性 ccRCC 患者的 OS 改善相关。
设计、设置和参与者：本队列研究于 2021 年 7 月 23 日最终确定，从 2006 年 1 月 1 日至 2016 年 12 月 31 日，在国家癌症数据库中确定了接受系统靶向治疗的转移性 ccRCC 患者。
接受细胞减灭性肾切除术。
主要结局是从诊断日期到死亡或最后一次随访时的死亡或删失的 OS。确定患者居住地邮政编码与治疗机构之间的距离作为有效的工具，并在两阶段剩余纳入工具变量分析中使用。为了进行比较，进行了常规的选择偏差调整、多变量 Cox 比例风险回归和倾向评分匹配。所有分析中调整的测量协变量包括年龄、性别、种族、Charlson-Deyo 评分、机构类型、诊断年份、临床 T 分期和临床 N 分期。
最终研究人群包括 12766 名患者（中位年龄，63 岁；IQR，56-70 岁；8744 名[68%]男性；11206 名[88%]白人）。5005 名患者（39%）接受了细胞减灭性肾切除术。常规选择偏差调整显示，细胞减灭性肾切除术与 OS 显著相关（多变量 Cox 比例风险回归：风险比[HR]，0.49；95%CI，0.47-0.51；倾向评分匹配：HR，0.48；95%CI，0.46-0.50）。工具变量估计未显示细胞减灭性肾切除术与 OS 之间存在关联（HR，0.92；95%CI，0.78-1.09）。
工具变量分析并未显示转移性 ccRCC 患者细胞减灭性肾切除术与生存获益相关。这种差异可能反映出细胞减灭性肾切除术的手术指征主要由观察性数据集通常无法测量或获取的因素驱动。
