Unraveling the BMI paradox in different renal cortical tumors: insights from the INMARC registry.

• The "obesity paradox" is not an observable phenomenon across different renal cortical tumors. • Obesity is not associated with improved survival and recurrence in nonclear cell renal cell carcinoma (RCC) and in nonmetastatic clear cell RCC while metastatic clear cell RCC patients with obesity had improved oncological outcomes, due to an increased metabolic reserve and associated heightened inflammatory state which could amplify treatment responses. To investigate impact of body mass index (BMI) on survival across different histologies and stages of renal cell carcinoma (RCC). We conducted a retrospective multicenter analysis of clear cell (ccRCC) and non-ccRCC. Obesity was defined according to the WHO criteria (non-Asian BMI >30 Kg/m2, Asian BMI >27.5 Kg/m2). Multivariable analysis (MVA) via Cox regression model was conducted for all-cause (ACM), cancer-specific mortality (CSM) and recurrence. A total of 3,880 patients with a median follow-up of 31 (IQR 9–64) months were analyzed. Overall, 1,373 (35.3%) were obese; 2,895 (74.6%) were ccRCC and 985 (25.3%) were non-ccRCC (chRCC 246 [24.9%], pRCC 469 [47.6%] and vhRCC 270 [27.4%]). MVA in ccRCC revealed obesity associated with decreased risk of ACM, CSM and recurrence (hazard ratio [HR] 0.80, P = 0.044; HR 0.71, P = 0.039; HR 0.73, P = 0.012, respectively), while in non-ccRCC was not associated with decreased risk of ACM, CSM, and recurrence (P = 0.84, P = 0.53, P = 0.84, respectively). Subset analysis in stage IV ccRCC demonstrated obesity as associated with a decreased risk of ACM, CSM, and recurrence (HR 0.68, P = 0.04; HR 0.59, P = 0.01; HR 0.59, P = 0.01, respectively), while in stage I–III ccRCC was not (P = 0.21; P = 0.30; P = 0.19, respectively). Our findings refute a broad "obesity paradox" for RCC. Obesity was not associated with improved survival in non-ccRCC and in nonmetastatic ccRCC, while metastatic ccRCC patients with obesity had improved survival outcomes. [ABSTRACT FROM AUTHOR]