Prognostic value of the C-PLAN index in patients with advanced esophageal cancer treated with immune checkpoint inhibitors.

[BACKGROUND] Despite significant advancements in immunotherapy for advanced esophageal cancer, there remains a critical need for reliable biomarkers to predict long-term clinical outcomes. The C-PLAN index, a novel composite score integrating C-Reactive Protein (CRP), lymphocyte dynamics, nutritional risk, and the Neutrophil-to-Lymphocyte Ratio (NLR), was developed to serve as a potential prognostic tool in this setting.

[METHODS] This study included 228 patients with advanced esophageal cancer who received PD-1/PD-L1 inhibitors between January 2018 and March 2023. Patients were stratified into low-risk (score ≤ 2), Medium-risk (score 3-4), or high-risk (score ≥ 5) groups based on the C-PLAN index. Clinical outcomes, including Overall Survival (OS) and Progression-Free Survival (PFS), were assessed over a 24-month follow-up period. Nonlinear associations between the C-PLAN index and OS/PFS were evaluated using restricted cubic splines. Cox proportional hazards models identified independent prognostic factors for OS, while time-dependent Receiver Operating Characteristic (ROC) curves compared the predictive accuracy of the C-PLAN index with that of NLR.

[RESULTS] Of the 228 patients enrolled, 189 were included in the final analysis. Significant differences in baseline characteristics were observed across risk groups: low-risk patients exhibited higher Body Mass Index (BMI) and albumin levels, whereas high-risk patients had larger tumor sizes, elevated CRP, Lactate Dehydrogenase (LDH), NLR, and C-PLAN scores. The median PFS was significantly longer in the low-risk group compared with intermediate- and high-risk groups (p < 0.001). A significant nonlinear relationship between the C-PLAN index and both OS and PFS was observed (p for nonlinearity < 0.001). Multivariable analysis identified NLR, poorly differentiated histology, and the C-PLAN index as independent predictors of mortality. Time-dependent ROC analyses revealed that the C-PLAN index demonstrated superior predictive accuracy compared to NLR at both 12-months (Area Under the Curve [AUC], 0.710 vs. 0.496) and 24-months (AUC, 0.897 vs. 0.740).

[CONCLUSION] The C-PLAN index provides a robust and clinically meaningful prognostic tool for patients with advanced esophageal cancer treated with immune checkpoint inhibitors. Its superior predictive performance compared to traditional markers such as NLR highlights its potential utility in risk stratification and guiding treatment decisions.