Body Mass Index as an Independent Prognostic Factor in Second-Line Nivolumab Therapy for Metastatic Clear Cell Renal Cell Carcinoma

Objective: Metastatic renal cell carcinoma (RCC) remains a therapeutic challenge despite significant advances with immune checkpoint inhibitors (ICIs). Nivolumab has demonstrated durable responses in pretreated metastatic clear cell RCC; however, prognostic and predictive biomarkers of response remain limited. Recent data suggest that increased body mass index (BMI) may correlate with improved survival outcomes in patients receiving ICIs, a phenomenon referred to as the “obesity paradox”. Material and Methods: This multicenter retrospective study evaluated the prognostic impact of BMI in 117 patients with metastatic clear cell RCC who received second-line nivolumab monotherapy following progression on prior tyrosine kinase inhibitor therapy. Results: The median BMI was 26.0 kg/m.; 40.3% were classified as underweight or normal, and 59.7% as overweight or obese. The median progression-free survival was 8.1 months [95% confidence interval (CI) 6.1-10.1], and the median overall survival (OS) was 24.7 months (95% CI 17.6-31.7). Overweight or obese (BMI ≥25 kg/m.) patients had longer OS than underweight or normal-weight patients (31.2 vs. 20.9 months, p=0.039). In the multivariate Cox regression analysis, higher Eastern Cooperative Oncology Group performance status (≥2), sarcomatoid differentiation, and liver and bone metastases were independent adverse prognostic factors, whereas higher BMI remained an independent favorable prognostic factor (HR=0.60, 95% CI 0.36-0.99, p=0.045). Conclusion: These results suggest that BMI may serve as a simple and clinically relevant prognostic marker in this population. Further large-scale prospective studies incorporating body composition and biomarker analyses are warranted to clarify the underlying mechanisms of this association.