Baseline and Dynamic Clinical–Laboratory Risk Models for Early Progression or Death during PD-(L)1 Blockade in Advanced NSCLC: Development and Internal Validation

Background: Tumour-growth kinetics required to diagnose hyperprogressive disease are often unavailable in routine care. We developed baseline and dynamic clinical–laboratory models for progression or death within 90 days (EPD90), a pragmatic endpoint for early clinical deterioration, and assessed whether six-week laboratory change improved risk estimation. Methods: This retrospective single-centre cohort included consecutive adults with advanced or unresectable non-small cell lung cancer treated with PD-1/PD-L1 blockade between January 2018 and March 2026. EPS-4 combined bone metastasis, lactate dehydrogenase (LDH) >240 U/L, albumin < 3.5 g/dL and C-reactive protein >10 mg/L. Day-42 landmark models added log2 ratios of neutrophil-to-lymphocyte ratio (NLR) and LDH. Performance was assessed with 2000 bootstrap resamples and repeated cross-validation. Results: Among 282 assessable patients, 83 (29.4%) had EPD90. In common complete cases (n = 252; 76 events), EPS-4 had an AUC of 0.729 (95% CI 0.665–0.793). Among 238 patients alive and progression-free at day 42 (56 subsequent events), AUC increased from 0.718 for EPS-4 alone to 0.801 after adding NLR change and 0.816 after adding LDH change. The final increment from LDH was modest (ΔAUC 0.016; P = 0.094). Conclusions: Baseline EPS-4 and early NLR change identified higher-risk patients, but the models remain development-stage and require independent prospective validation.