Surgery Does Not Increase Survival in Stage 4 Kidney Cancer

Metastatic (stage 4) clear cell kidney cancer patients did not have improved overall survival after kidney removal, as shown by a study published in JAMA Network Open on 16 May 2022 and involving about 13 thousand patients... New and more effective systemic treatment options are available for kidney cancer.

As a general rule in oncology, once cancer reaches stage 4 — meaning it has spread to other organs and tissues — it is known that surgery will no longer be beneficial. For some specific cancers, there is weak evidence that removing the primary tumor surgically may be beneficial even at stage 4; kidney cancer was one of them. The study discussed in this article used "instrumental variable analysis" to correct bias caused by unmeasured variables and reached results that contradicted findings from earlier observational datasets.

A further analysis of the study, involving 12,766 patients with a median age of 63, 68% of whom were men and 88% white, showed no association between kidney removal and overall survival (HR, 0.92; 95% CI, 0.78-1.09).

This inconsistency with earlier findings probably reflects the fact that eligibility for "cytoreductive nephrectomy," surgery to reduce tumor burden in advanced kidney cancer, is largely driven by factors that are unmeasured or unavailable in observational datasets.

For decades, cytoreductive nephrectomy has been the standard initial treatment approach for patients with metastatic clear cell kidney cancer who do not have poor-risk disease. Tyrosine kinase inhibitor targeted drugs were in their early days when several large observational studies showed that cytoreductive nephrectomy continued to offer a significant overall survival benefit. However, these studies did not account for selection bias in choosing patients suitable for surgery.

For this new study, researchers identified 12,766 cases of clear cell kidney cancer in the National Cancer Database, which includes more than 70% of cancer cases diagnosed in the United States from 1 January 2006 to 31 December 2016. They assessed the effect of cytoreductive nephrectomy on overall survival in patients with metastatic clear cell kidney cancer using instrumental variable analysis to compare it with results produced by conventional adjustments for selection bias.

Instrumental variables are used in observational studies to control confounding and measurement error. In this study, increasing distance to the treatment center was an important instrumental variable (P < 0.001). As the distance to a hospital increased, so did the proportion of patients undergoing cytoreductive nephrectomy. This was probably because patients preferred surgery as a more radical choice over systemic therapies requiring frequent visits, in order to visit hospitals less often.

But the study showed, consistently with the most up-to-date evidence, that instrumental variable analysis found no association between cytoreductive nephrectomy and improved overall survival in patients with metastatic clear cell kidney cancer.

After 2016

It should also be remembered that this study did not measure the survival contribution of new drugs approved for kidney cancer after 2016. These new treatments have significantly improved survival rates in advanced kidney cancer compared with 10 years earlier, reinforcing the place of systemic drugs as first-line treatment.

*

Manage preferences to view external content