Integrated Inflammatory and Nutritional Biomarkers in Metastatic Renal Cell Carcinoma Treated with Second- or Later-Line Nivolumab: A Retrospective Cohort Study

Background and Objectives: During the 2016–2022 period, tyrosine kinase inhibitor (TKI) monotherapy was the standard first-line option at our center before combination protocols became available. This study evaluates patients experiencing initial TKI failure who subsequently received second- or later-line nivolumab. Because clinical practice lacks low-cost, accessible tools to prognosticate outcomes in this setting, we evaluated whether baseline psoas muscle index (PMI), early on-treatment C-reactive protein (CRP) kinetics, and a specific panel of blood-derived inflammatory/nutritional ratios offer reliable prognostic value. Materials and methods: We retrospectively reviewed data from 49 consecutive mRCC patients who progressed on a TKI and received second- or later-line nivolumab monotherapy. Primary endpoints were overall survival (OS; N = 49) and time-to-treatment failure (TTF; N = 48). We utilized Kaplan–Meier and Cox regression models for analysis. Benjamini–Hochberg false discovery rate (FDR) correction (q < 0.05) controlled false positive inflation across two separate testing frameworks: seven log-rank assessments for TTF and the core Cox models. Adjusted models accounted for clinical covariates including International Metastatic RCC Database Consortium (IMDC) risk category, Eastern Cooperative Oncology Group performance status (ECOG PS), and de novo metastatic presentation. We calculated the intraclass correlation coefficient (ICC) to evaluate measurement reproducibility. Results: Median follow-up reached 48.4 months (reverse Kaplan–Meier; maximum: 87.8 months), with a cohort-wide median OS of 13.9 months (IQR: 5.8–36.2). A low baseline C-reactive protein-to-albumin ratio (CAR) mapped to a distinct survival benefit, showing a median OS of 32.6 months versus 5.8 months in the high-CAR group (log-rank p < 0.001; BH q = 0.003). In adjusted multivariable Cox hazards modeling, both CAR (HR: 1.029; p = 0.002) and the prognostic nutritional index (PNI; HR: 0.893; p < 0.001) maintained independent prognostic significance. When evaluating the 43 patients with complete 3-month CRP records, we found a significantly higher objective response rate (ORR) in those at or below the cohort-median ratio threshold of 1.16 compared to patients above it (54.5% vs. 23.8%; p = 0.039). The overall ITT population registered an ORR of 36.7% (18/49). Conclusions: Low pretreatment CAR and elevated PNI identify mRCC patients showing improved survival profiles in this post-TKI nivolumab subgroup. Additionally, an elevated 3-month CRP ratio correlates with compromised objective response rates and a trend toward shorter TTF, though the TTF endpoint did not clear strict FDR parameters (BH q = 0.098). These retrospective, single-center data serve strictly for signal generation and require independent prospective multi-institutional confirmation before translating to oncology practice.