Multivariable model for predicting 5-year survival in patients with EGFR-mutated non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: a retrospective study.

Background: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. In Asian populations, epidermal growth factor receptor (EGFR) mutations are particularly prevalent, leading to the development of EGFR tyrosine kinase inhibitors (TKIs) to improve patient outcomes. While extensive research has been conducted on the prognosis of patients receiving EGFR-TKIs, the estimation of 5-year survival in this population remains an underexplored area.

Objectives: This study aimed to provide real-world evidence and conduct a comprehensive analysis of the determinants influencing the 5-year survival rate in patients with EGFR-mutated NSCLC. Considering the factors identified in this study, a scoring system was developed to predict the likelihood of patients achieving this goal.

Design: A retrospective cohort study utilizing a training cohort of 1,873 patients and a validation cohort of 484 patients.

Methods: A logistic regression model was constructed to evaluate the weighting of factors and develop a scoring system. The Kaplan-Meier model estimated the overall survival probability, and patients were categorized into four risk groups based on their likelihood of five-year survival. The prediction performance of both the training and validation cohorts was evaluated using the area under the curve (AUC), accuracy, precision, sensitivity, specificity, and F1-score.

Results: Results indicated that age > 65 years; performance score of 2-4; metastasis to the liver, brain, bone, or pleura; and poor disease control were associated with a decreased likelihood of 5-year survival. The estimated 5-year survival rate was 23.4% (odds ratio [OR]: 20.56; 95% confidence interval [CI]: 9.06-46.64; p < 0.0001), 16.1% (OR: 12.88; 95% CI: 5.82-28.49; p < 0.0001), 7.2% (OR: 5.23; 95% CI: 2.36-11.60; p < 0.0001), and 1.5% (OR: reference) for the low-risk, intermediate-risk, high-risk, and very-high-risk groups, respectively. The validation cohort further confirmed these findings, showing survival probabilities of 52.6% (OR: 96.67; 95% CI: 11.07-844.23; p < 0.0001), 21.3% (OR: 23.49; 95% CI: 3.13-176.46; p = 0.002), 14.9% (OR: 15.21; 95% CI: 2.03-114.25; p = 0.008), and 1.1% (OR: reference) for the low-risk, intermediate-risk, high-risk, and very-high-risk groups, respectively. The training cohort demonstrated an AUC of 0.79 (95% CI: 0.75-0.82) and a model quality score of 0.75, indicating good predictive performance. Calibration plots demonstrated a good fit for the scoring system. For the external validation cohort, the AUC, precision, sensitivity, and specificity were 0.71, 0.74, 0.35, 0.33, respectively. The model achieved an F1-score of 0.47, reflecting adequate performance in predicting 5-year survival probabilities.

Conclusion: This study identified critical prognostic factors and developed a validated scoring system for estimating 5-year survival in patients with EGFR-mutated NSCLC receiving EGFR-TKIs. While the model demonstrated robust predictive performance within the study cohort, broader applicability beyond Taiwan may require further refinements and alternative study designs.