Real-World Predictors of Response to Immunotherapy in Metastatic Renal Cell Carcinoma: The Emerging Role of the Urologist in Immuno-Oncology

Celia Abad Rodriguez-Hesles,1,2 Francisco Gutierrez-Tejero,1 Virginia Yuste-Mascarós,1 Alberto Zambudio-Munuera,1 Miguel Arrabal-Martin,1,2 Miguel Angel Arrabal-Polo1,2 1Department of Urology, Hospital Clínico San Cecilio, Granada, Spain; 2Uromet Group Research, Biomedic Research Institute Granada (IBS Granada), Granada, SpainCorrespondence: Miguel Angel Arrabal-Polo, Department of Urology, Hospital Clínico San Cecilio, Granada, Spain, Tel +34 628 837 188, Email [email protected]: Immunotherapy has transformed the treatment of metastatic renal cell carcinoma (mRCC), with urologists playing a central role in systemic treatment selection through multidisciplinary decision-making, patient selection, and treatment sequencing. Identifying predictors of response is essential to personalize therapy and improve outcomes.Material and Methods: We conducted a retrospective, single-center study of 32 patients with mRCC who received immunotherapy: 15 received first-line nivolumab-ipilimumab, 3 pembrolizumab-axitinib, 13 second-line nivolumab, and 1 third-line nivolumab. Clinical, histological, and prognostic variables (International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), Meet-URO, FAN score), and blood biomarkers (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), eosinophil percentage) were assessed using Kaplan-Meier analysis with Log rank tests and Cox regression. Given the small sample size, results should be interpreted with caution.Results: A total of 32 patients were included, with the majority classified as IMDC intermediate risk. The Meet-URO score showed superior prognostic value for overall survival compared with IMDC (median 21 vs. 1– 2 months across groups; 95% CI 1.83– 20.17; p=0.043). A post-treatment NLR below 2.44 predicted improved progression-free survival (median 17 vs. 7 months; 95% CI 7.4– 26.2; p=0.014) and remained independently significant. Neither FAN score nor eosinophil percentage provided prognostic discrimination. No survival differences were observed between treatment lines. Cytoreductive nephrectomy (78%) was associated with longer progression-free survival (9 vs. 3 months; HR: 3.72, 95% CI 1.15– 12.02; p=0.028) and overall survival (21 vs. 3 months; HR 4.03, 95% CI 1.14– 14.19; p=0.030).Conclusion: Cytoreductive nephrectomy, early NLR, and the Meet-URO score may have potential value for risk stratification in patients with mRCC receiving immunotherapy. In a real-world urology-led setting, these factors may support clinical decision-making and treatment selection. These findings should be considered exploratory and hypothesis-generating, given the limited sample size, and warrant confirmation in larger prospective studies.Keywords: renal cell carcinoma, immunotherapy, neutrophil-to-lymphocyte ratio, cytoreductive nephrectomy, survival analysis, urologic oncology