Sercan ÖN, Mehmet Cihan İÇLİ, Tuğçe ULAŞLI, Gökhan ŞAHİN, Aslı GEÇGEL, Burcu ÇELİKTEN QUIGLEY, Yiğit Efe SÜRGEN, Hasan Çağrı YILDIRIM, Hüseyin Salih SEMİZ, Mustafa ERMAN, Erhan GÖKMEN
Journal of Oncological Sciences - 2025;11(3):269-275
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.
