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: We developed clinical–laboratory models for early progression or death within 90 days (EPD90) during PD-1/PD-L1 blockade in advanced non-small cell lung cancer. EPD90 is a pragmatic early-risk endpoint, not a diagnosis of hyperprogressive disease. Methods: This retrospective single-centre cohort included patients treated between January 2018 and March 2026. The four-item baseline score, EPS-4, combined bone metastasis, lactate dehydrogenase (LDH), albumin and C-reactive protein. Among patients alive and progression-free at day 42, D1 added six-week changes in neutrophil-to-lymphocyte ratio (NLR), and D2 additionally included LDH changes. Internal validation used bootstrap resampling and repeated cross-validation. Results: Among 282 patients, 83 (29.4%) had EPD90. In the common baseline complete-case set (n = 252; 76 events), EPS-4 had an apparent area under the curve (AUC) of 0.729 (95% confidence interval [CI] 0.665–0.793). In 238 landmark-eligible complete cases (56 subsequent events), adding NLR change increased AUC from 0.718 to 0.801. Adding LDH yielded an AUC of 0.816, a modest, statistically non-significant increment (delta AUC 0.016; p = 0.094). Bootstrap-corrected calibration slopes were 0.980 for D1 and 0.957 for D2. Conclusions: NLR provided the principal dynamic contribution. D1 is emphasized as the main dynamic model; D2 remains an exploratory extension with uncertain incremental value. Unavailable laboratory collection dates and lack of external validation limit interpretation. The models and proposed thresholds require independent validation before clinical use.