C-reactive Protein to Albumin Ratio as a Prognostic Biomarker in Patients with Esophageal Squamous Cell Carcinoma Receiving Immune Checkpoint Inhibitor- based Therapy

Background The C-reactive protein to albumin ratio (CAR) reflects systemic inflammation and nutritional status, but its prognostic value in esophageal squamous cell carcinoma (ESCC) treated with immune checkpoint inhibitor (ICI)-based therapy remains unclear. Methods We retrospectively analyzed 199 patients with unresectable advanced or recurrent ESCC who received ICI-based therapy across three cohorts: second- or later-line nivolumab monotherapy (n = 107), first-line chemotherapy plus ICI (n = 60), and first-line nivolumab plus ipilimumab (n = 32). The CAR cutoff values were determined using time-dependent receiver operating characteristic curve analysis. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methods and Cox proportional hazards models. Results In the nivolumab monotherapy cohort, patients with a low CAR (< 0.072) had significantly better PFS (median 5.6 vs. 1.9 months; p = 0.001) and OS (median 20.0 vs. 5.5 months; p < 0.01) than those with a high CAR. In the first-line chemotherapy plus ICI cohort, patients with a low CAR (< 0.090) were associated with longer OS (median, 21.2 vs. 8.8 months; P = 0.03). A similar association was observed in the nivolumab plus ipilimumab cohort (median OS, 22.3 vs. 13.1 months; P = 0.003). In multivariable analyses, CAR remained an independent prognostic factor for OS in both the nivolumab monotherapy cohort (hazard ratio (HR) 2.36; 95% confidence interval (CI) 1.35–4.12; p = 0.002) and the first-line cohort (HR 2.38; 95% CI 1.24–4.56; p = 0.009). Patients with a high CAR were more likely to transition directly to best supportive care after discontinuing ICI-based therapy. Conclusions CAR is a simple, reliable, and independent prognostic biomarker in patients with unresectable advanced or recurrent ESCC receiving ICI-based therapy.