Selection Instability and External Performance of Transcriptomic Models Beyond Age, Sex and Stage in Resected Lung Adenocarcinoma

Background/Objectives: We evaluated molecular selection stability and external prediction beyond age, sex and broad pathological stage in resected stage I–II lung adenocarcinoma.

Methods

Models were developed in 228 patients from two sources and frozen before evaluation in four historical cohorts containing 778 patients. The primary comparison added pathway scores using elastic-net Cox regression. Secondary analyses examined a gene model, 200 development bootstrap resamples, alternative modeling specifications and locally updated baselines. Prediction error was measured by the integrated Brier score over 1–3 years (IBS); negative molecular-minus-clinical differences (ΔIBS) favored molecular models. Evaluation intervals used 2000 paired bootstrap resamples.