Survival Outcomes Associated With Cytoreductive Nephrectomy in Patients With Metastatic Clear Cell Renal Cell Carcinoma

Key Points

Question

Is cytoreductive nephrectomy associated with improved overall survival for patients with metastatic clear cell renal cell carcinoma?

Findings

In this cohort study of 12 766 patients, receipt of a cytoreductive nephrectomy was not associated with improved overall survival using instrumental variable analysis to adjust for bias due to unmeasured confounding. Methods that do not adjust for this bias would have suggested a substantial overall survival benefit.

Meaning

Consistent with contemporary Level I evidence, instrumental variable analysis demonstrated that cytoreductive nephrectomy was not associated with improved overall survival for patients with metastatic clear cell renal cell carcinoma.

Abstract

This cohort study of patients with metastatic clear cell renal cell carcinoma assesses whether cytoreductive nephrectomy is associated with improved overall survival.

Abstract

Importance

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.

Objective

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.

Exposures

Receipt of cytoreductive nephrectomy.

Main Outcomes and Measures

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.

Results

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).

Conclusions and Relevance

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.