Too good for CARMENA: criteria associated with long systemic therapy free intervals post cytoreductive nephrectomy for metastatic clear cell renal cell carcinoma.

Purpose: The prospective CARMENA trial surprisingly suggested that patients with upfront metastatic clear-cell renal cell carcinoma (m-ccRCC) would not benefit from cytoreductive nephrectomy (CN). We aimed to identify the m-ccRCC patient subpopulation who would benefit from the continued use of CN.

Methods: We performed a retrospective cohort study on upfront m-ccRCC patients and identified three subgroups: patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) only without CN (TKI ONLY), patients undergoing CN immediately followed within 6 months by VEGFR-TKIs (CN > TKI) and patients undergoing CN followed by a considerable therapy-free interval of at least 6 months (CN > AS). Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare outcomes and investigate predictive factors.

Results: We included 119 patients. Overall survival was 17, 13 and 56 months for the CN > TKI, TKI only and CN > AS subgroups, respectively ( < 0.0001). Oligometastatic disease (HR = 0.33, 95% CI = 0.21-0.54,  < 0.0001), lung as only metastatic site (HR = 0.48, 95% CI = 0.31-0.76,  = 0.001) and having ≤ 2 evaluable International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria (HR = 0.56, 95% CI = 0.32-0.98,  = 0.04) were predictive for systemic therapy free survival after diagnosis.

Conclusions: The CARMENA results only apply for m-ccRCC patients in immediate need for systemic therapy, but not for patients in whom a period of AS can be expected after CN. Patients in whom systemic therapy most likely can be deferred and who are likely to benefit from CN have oligometastatic disease, only present in the lung and few (≤2) evaluable IMDC criteria.