Beril Balci Topuz, Ahmet Tufekci, Sibel Cangi, Ömer Aydın Yıldırım, Mustafa Yildirim
Background/Objectives: Systemic inflammation, nutritional status, and immune competence have emerged as important prognostic determinants in metastatic renal cell carcinoma (mRCC). The C-reactive protein–albumin–lymphocyte (CALLY) index integrates these parameters into a single composite biomarker, yet its utility in mRCC remains insufficiently explored. This study aimed to evaluate the prognostic significance of the CALLY index in mRCC and its associations with clinicopathological features and survival outcomes. Methods: A total of 68 patients with mRCC treated between 2017 and 2024 were retrospectively analyzed. All patients received first-line VEGF–TKI therapy, and 73.5% subsequently received second-line treatment, predominantly nivolumab. The CALLY index was calculated as (albumin × lymphocyte count)/(CRP × 104), and patients were stratified using the median cut-off (0.16). Survival outcomes were assessed with Kaplan–Meier and Cox regression analyses. Discriminative performance was evaluated using Harrell’s C-index and time-dependent ROC curves at 6, 12, and 24 months. Results: Low CALLY (≤0.16) was significantly associated with shorter PFS (4 vs. 8 months, p < 0.001) and OS (9 vs. 26 months, p < 0.001). In multivariate analysis, the CALLY index independently predicted both PFS (HR = 1.91, p = 0.045) and OS (HR = 2.89, p = 0.005). Time-dependent ROC analysis demonstrated increasing discriminative strength for PFS (AUC: 0.70 → 0.95) and modest decline for OS over time (AUC: 0.83 → 0.72). CALLY also showed strong associations with IMDC risk classification and peritoneal metastasis. Conclusions: The CALLY index is a simple, cost-effective, and objective prognostic biomarker that may independently predict progression and survival in mRCC. Its complementary value to the IMDC model supports its integration into routine risk stratification and real-world clinical decision-making.