Association Between Pathologic Response and Survival Following Neoadjuvant Targeted Therapy in Epidermal Growth Factor Receptor-Mutant Lung Adenocarcinoma

OBJECTIVES: The International Association for the Study of Lung Cancer (IASLC) recommended applying a 10% residual viable tumour (%RVT) threshold for major pathological response (MPR) to all therapies. However, evidence supporting the association between pathological regression and prognosis after neoadjuvant targeted therapy is lacking. METHODS: This study retrospectively included 228 patients with epidermal growth factor receptor-mutant adenocarcinoma receiving neoadjuvant targeted therapy. The optimal %RVT cutoff for predicting recurrence-free survival (RFS) was determined using maximally selected rank statistics and Youden's index. RFS was evaluated utilizing Kaplan-Meier methods and Cox proportional hazard analyses. RESULTS: The median %RVT was 50%, with 17% of patients achieving MPR. Patients with %RVT ≤ 10% (MPR) had a significantly better RFS than those with %RVT > 10% (non-MPR) (P = .012). Moreover, the optimal %RVT cutoff for RFS was 75%. Multivariable analysis revealed that %RVT > 75% was an independent risk factor for RFS (P = .045). When stratified by 10% and 75% RVT, patients with %RVT > 75% had the worst RFS, followed by those with %RVT 10%-75%, while patients with %RVT ≤10% had the best survival (P = .0023). The IASLC adenocarcinoma grading system retained prognostic significance after targeted therapy (P < .0001) and was confirmed as an independent prognostic factor (P = .006). It also exhibited synergistic prognostic value with a 10% RVT (P < .0001). CONCLUSIONS: This study verified the association between tumour regression and prognosis after neoadjuvant targeted therapy. A 10% RVT threshold stratified the prognosis, validating the IASLC's MPR for use in neoadjuvant targeted therapy, while a 75% RVT cutoff also proved useful for prognostic discrimination. These findings require validation by prospective studies.