Clinical Impact of the CARMENA Trial on Cytoreductive Nephrectomy Practices in the USA: A Difference-in-differences Analysis.

Abstract

Background and objective: It is unclear whether cytoreductive nephrectomy (CN) practices have changed in the USA after the publication of the Cancer du Rein Métastatique Nephrectomie et Antiangiogéniques (CARMENA) trial in 2018. Our primary objective is to determine the effect of the CARMENA trial on CN rates in the USA.

Methods: Patients were identified in the National Cancer Database from 2004 to 2020. A quasiexperimental difference-in-differences analysis was used to test the primary outcome, as follows: the change in CN rate was assessed among metastatic clear cell renal cell carcinoma (ccRCC) patients diagnosed before versus after 2018, while using the localized nephrectomy (LN) rate performed in the setting of nonmetastatic ccRCC as a control group.

Key findings and limitations: The difference-in-differences analysis identified a statistically significant decrease in CN rate after CARMENA (β-coefficient [standard error]: -0.06 [0.025], p = 0.028), with a 10.2% absolute and a 31.8% relative rate reduction when compared with the counterfactual (expected) value (34.7% → 21.9% [actual] vs 32.1% [expected]). Primarily, relative differences in CN and LN rates before and after 2018 may be attributable to additional factors, aside from CARMENA publication, not tested in this quasiexperimental model.

Conclusions and clinical implications: CN rates decreased significantly after the publication of the CARMENA trial in 2018, with a minimal difference in regional or demographic practice patterns. Overall, the publication of the CARMENA trial results is seemingly associated with substantial alteration of clinical practice in the USA, with relatively broad and nonspecific adoption across facilities, regions, and demographics.

Patient summary: For decades, the immediate surgical removal of the kidney tumor (cytoreductive nephrectomy) was a mainstay of metastatic kidney cancer treatment. In 2018, the CARMENA study showed that patients treated with systemic therapy alone had similar outcomes to patients who underwent cytoreductive nephrectomy first. In this study, we show that fewer cytoreductive nephrectomies were performed after the CARMENA trial results were published.