Researchers writing in JAMA Network Open report that for patients with metastatic clear cell renal cell carcinoma, removal of the kidney and its primary tumor is not associated with improved overall survival.

The result, which was derived using instrumental variable analysis to adjust for bias due to unmeasured variables, contradicts results from previous observational datasets.

“These observational studies did not account for selection bias related to unmeasured confounding by surgical indication, and as such their results may not accurately reflect the effectiveness of the intervention,” the authors wrote, led by Nicholas H. Chakiryan, MD, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Primary outcome analysis using conventional adjustments for selection bias in the final study population of 12,766 patients (median age 63 years, 68% male, 88% Caucasian) revealed that nephrectomy Cytoreductive therapy performed in 5005 patients (39%) was associated with a survival benefit (multivariate regression of Cox proportional hazards: risk ratio [HR], 0.49; 95% confidence interval [CI], 0.47-0.51; propensity score matching: HR, 0.48; 95% CI, 0.46-0.50). Analysis using instrumental variable estimates, however, failed to demonstrate an association between cytoreductive nephrectomy and overall survival (HR, 0.92; 95% CI, 0.78-1.09). “This discrepancy likely reflects the fact that the surgical indication for cytoreductive nephrectomy is primarily driven by factors that are not commonly measured or available in observational data sets,” Chakiryan and colleagues wrote.

For surgical candidates for metastatic clear cell renal cell carcinoma (ccRCC) without low-risk disease, cytoreductive nephrectomy has been a clinical standard for decades. Several large observational studies conducted during the current era of post-cytokine tyrosine kinase-inhibiting targeted therapy have demonstrated that cytoreductive nephrectomy continues to provide a substantial benefit in terms of overall survival. However, these studies did not take into account the selection bias linked to confusion not measured by surgical indication.

The researchers identified 12,766 cases of ccRCC from the National Cancer Database, which includes more than 70% of newly diagnosed cancer cases in the United States from January 1, 2006 through December 31, 2016. Their main objective was to assess the effect of cytoreductive nephrectomy on the overall survival of patients with metastatic ccRCC using instrumental variable analysis to adjust for unmeasured confounders and compare these results with those generated by conventional adjustments for bias. selection.

Instrumental variables are used to control for confounding factors and measurement errors in observational studies. In this study, increasing distance to the treatment facility was a significant instrumental variable (P

“Consistent with contemporary Level 1 evidence, instrumental variable analysis demonstrated that cytoreductive nephrectomy was not associated with improved overall survival in patients with metastatic clear cell renal cell carcinoma,” the authors concluded. authors.

Among the limitations of the analysis, they noted that instrumental variable analyzes functionally compare marginal patient populations within the overall cohort, which potentially limits the generalizability of the results.

This story originally appeared on MDedge.com, part of the Medscape Professional Network.