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 = 0.012). Moreover, the optimal %RVT cutoff for RFS was 75%. Multivariable analysis revealed that %RVT > 75% was an independent risk factor for RFS (P = 0.045). 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 = 0.0023). The IASLC adenocarcinoma grading system retained prognostic significance after targeted therapy (P < 0.0001) and was confirmed as an independent prognostic factor (P = 0.006). It also exhibited synergistic prognostic value with a 10% RVT (P < 0.0001). 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.