Overall survival prediction and risk stratification for advanced EGFR-mutant lung adenocarcinoma patients treated with first-line tyrosine kinase inhibitors

Background Lung adenocarcinoma (LAD) is the most common non-small cell lung cancer subtype, with frequent epidermal growth factor receptor (EGFR) mutations in Asians. First-line tyrosine kinase inhibitors (TKIs) improves survival but resistance is inevitable, leading to disease progression and even death. We aimed to develop a predictive model for overall survival (OS) and prognostic risk stratification. Methods In this retrospective study, patients with stage IIIB-IV EGFR-mutant LAD who received first-line TKIs and underwent pretreatment contrast-enhanced thoracic CT between January 2015 and April 2024 were enrolled. Clinicoradiological findings associated with OS were evaluated using multivariate Cox regression. The performance of the Cox regression model was assessed using the time-dependent area under the curve (AUC) and Harrell’s concordance index (C-index). Nonparametric bootstrapping with 1000 resamples was performed as internal validation to evaluate the robustness and discriminative ability of the model. Results A total of 250 patients (105 males and 145 females) with a mean age of 61 ± 11 years were included. The median OS was 33 (95% CI 25–37) months in patients with advanced EGFR-mutant LAD receiving TKIs. Among the EGFR subtypes, the exon 21-L858R mutation was associated with greater mortality than the exon 19- deletion mutation (HR = 1.541, P = 0.030). Age ≥ 60 years (HR = 1.682, P = 0.003), and CYFRA21-1 ≥ 4.5 ng/mL (HR = 1.767, P = 0.005) were associated with relatively high mortality risk. Treatment with third-generation EGFR-TKIs (HR = 0.476, P < 0.001) was associated with a decreased mortality risk compared with first/second-generation EGFR-TKIs. We further constructed a nomogram for predicting 12-, 24-, 36-, and 48-month OS with the AUCs of 0.745, 0.717, 0.645, and 0.673, respectively. The global C-index was 0.674. The internally validated corrected global C-index was 0.662, and the AUCs for predicting 12-, 24-, 36-, and 48-month OS were 0.766, 0.714, 0.631, and 0.672, respectively. The high-risk group had a higher risk of mortality than the low-risk group (HR = 2.558, P < 0.001). Conclusion Nomogram including age, EGFR genotype, serum CYFRA21-1 level, and EGFR-TKI generation can predict OS and facilitate risk stratification in patients with advanced EGFR-mutated LAD receiving first-line TKIs. Clinical trial number Not applicable