Cytoreductive nephrectomy imparts no survival benefit in metastatic renal cell carcinoma patients: JAMA

USA: A new study published in the Journal of American Medical Association (JAMA) shows that an examination of instrumental variables revealed no survival benefit related to cytoreductive nephrectomy in patients with metastatic clear cell renal cell carcinoma (ccRCC).

In the modern period, Level I evidence has failed to establish an overall survival (OS) advantage for cytoreductive nephrectomy in patients with metastatic clear cell renal cell carcinoma (ccRCC), despite observational studies suggesting a significant OS benefit associated with these procedures. These studies were not intended to account for unmeasured confounding. As a result, Nicholas H. Chakiryan and colleagues undertook this study to see if cytoreductive nephrectomy is related to better overall survival in patients with metastatic ccRCC.

From January 1, 2006, to December 31, 2016, patients with metastatic ccRCC who underwent systemic targeted treatment were identified in the National Cancer Database. On July 23, 2021, the analysis was completed. The primary outcome was time from diagnosis to death or censoring at the final follow-up. Distance from the patient's zip code to the treatment facility was recognized as a valid instrument and utilized in a 2-stage residual inclusion instrumental variable analysis.

The key findings of this study were as follows:

1. The total number of patients in the trial was 12 766. In 5005 patients, cytoreductive nephrectomy was done (39%).

2. Adjusting for selection bias revealed a substantial OS improvement associated with cytoreductive nephrectomy.

3. The instrumental variable estimates did not show a link between cytoreductive nephrectomy and OS.

In conclusion, consistent with the findings of the CARMENA trial, instrumental variable estimates in this cohort research did not show a survival benefit linked with cytoreductive nephrectomy for patients with metastatic ccRCC. Methods that did not account for unmeasured confoundings, such as multivariable Cox proportional hazards regression and propensity score matching, revealed a significant advantage from cytoreductive nephrectomy. This disparity is most likely due to the fact that the surgical rationale for cytoreductive nephrectomy is predominantly determined by characteristics that are seldom assessed or available in observational data sets.

Reference:

Chakiryan, N. H., Gore, L. R., Reich, R. R., Dunn, R. L., Jiang, D. D., Gillis, K. A., Green, E., Hajiran, A., Hugar, L., Zemp, L., Zhang, J., Jain, R. K., Chahoud, J & Gilbert, S. M. (2022). Survival Outcomes Associated With Cytoreductive Nephrectomy in Patients With Metastatic Clear Cell Renal Cell Carcinoma. In JAMA Network Open (Vol. 5, Issue 5, p. e2212347). American Medical Association (AMA). https://doi.org/10.1001/jamanetworkopen.2022.12347