Prediction of immunotherapy efficacy for pulmonary lymphoepithelioma-like carcinoma using baseline routine blood tests and serum tumor markers: a multicenter retrospective study.

Background: Pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare Epstein-Barr virus-associated subtype of non-small cell lung cancer. Although immune checkpoint inhibitors (ICIs) have shown promising activity, robust predictors of benefit remain lacking. Programmed death-ligand 1 (PD-L1) is widely used but has limited accuracy. Routine blood tests and serum tumor markers (STMs) are inexpensive and universally available, yet their prognostic value in pLELC has not been systematically evaluated. Objectives: To develop and validate a composite blood-based score integrating hematologic indices and STMs for predicting immunotherapy outcomes in advanced pLELC. Design: Multicenter retrospective cohort study. Methods: We retrospectively analyzed 254 patients with advanced pLELC treated with ICIs across six tertiary centers in China. Baseline hematologic indices, serum biochemistry, and STMs were collected. A composite Blood Routine & Tumor-Marker Score (BRTS) was constructed using LASSO Cox regression with progression-free survival (PFS) as the endpoint. Patients were stratified into high- and low-BRTS groups, and prognostic value was validated in an independent cohort. Nomograms combining BRTS with clinical variables were developed and internally validated. Results: High BRTS was associated with significantly shorter PFS and overall survival (OS) in both training (hazard ratio (HR) for PFS = 4.59; OS = 6.86) and validation cohorts (HR for PFS = 5.37; OS = 3.87; all p < 0.001). In multivariate analyses, BRTS remained an independent predictor alongside treatment line, regimen, and liver metastasis, whereas PD-L1 expression lost significance. Nomograms incorporating BRTS demonstrated good discrimination (C-index ~0.79), calibration, and clinical net benefit. Prognostic utility was consistent across treatment lines. Conclusion: The BRTS, derived from widely available laboratory tests, robustly stratified immunotherapy outcomes in advanced pLELC and outperformed PD-L1 alone. This simple, low-cost tool may facilitate individualized treatment decisions and warrants prospective validation.