Early Post-Treatment Eosinophil Elevation and Survival Outcomes in Metastatic Renal Cell Carcinoma Treated with First-Line VEGFR-TKI Monotherapy: A Turkish Multicenter Retrospective Cohort Study

Background/Objectives: We aimed to evaluate the association between early post-treatment eosinophil (Eo) elevation and survival outcomes in metastatic renal cell carcinoma (mRCC) treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). We also assessed whether early post-treatment Eo elevation provided prognostic information beyond the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model. Methods: This Turkish retrospective multicenter cohort study included 280 patients with mRCC who received first-line VEGFR-TKI monotherapy between 2015 and 2025. Early post-treatment Eo elevation was defined as a post-baseline Eo percentage >5% in the complete blood count obtained within 15 days before the first computed tomography assessment performed for response/progression evaluation. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods and compared with log-rank tests. Cox regression models assessed independent prognostic associations. Time-dependent receiver operating characteristic (ROC) curve analyses were performed to evaluate the incremental prognostic value of early post-treatment Eo elevation beyond IMDC risk. Results: The median age was 61 years, and 205 patients (73.2%) were male. Early post-treatment Eo elevation was observed in 88 patients (31.4%). Median PFS was longer in patients with early post-treatment Eo elevation than in those without Eo elevation (15.1 vs. 10.1 months; p < 0.001). Median OS was also longer in the Eo elevation group (70.0 vs. 38.6 months; p < 0.001). In multivariable analysis, early post-treatment Eo elevation remained independently associated with improved PFS (hazard ratio HR: 0.60, 95% confidence interval CI: 0.44–0.81, p = 0.001) and OS (HR: 0.51, 95% CI: 0.33–0.80, p = 0.004). The combined IMDC plus Eo model showed higher time-dependent area under the curve values than the IMDC model alone. Conclusions: Early post-treatment Eo elevation was independently associated with improved PFS and OS, and the combined model showed greater prognostic discrimination than IMDC risk alone. Given that Eo status was assessed after treatment initiation, residual selection bias cannot be excluded, and prospective validation is required before clinical implementation.