Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide. Approximately one-third of patients are diagnosed at a locally advanced, initially unresectable stage. With the increasing application of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in advanced and adjuvant settings, their role in the “conversion therapy” phase—i.e., transforming unresectable tumors into resectable ones through drug-induced downstaging—has drawn growing attention. However, there is still a lack of systematic and sufficient evidence regarding the safety, feasibility, and potential survival benefits of conversion surgery after EGFR-TKI induction therapy in EGFR-mutant, locally advanced NSCLC. This study aims to evaluate the efficacy and safety of conversion surgery following EGFR-TKI induction therapy in this population, providing scientific evidence for optimizing comprehensive treatment strategies.

This retrospective cohort study included patients with stage IIIA-N2 to IIIC EGFR-mutant NSCLC who received EGFR-TKI therapy between January 2017 and December 2022. All patients were deemed unresectable by a multidisciplinary team (MDT) prior to treatment and received at least two cycles of EGFR-TKI monotherapy or combined chemotherapy. Patients who were considered resectable after MDT reassessment were included in the conversion surgery group; those who remained on systemic therapy formed the non-surgical control group. The primary endpoints included: (1) surgical safety (perioperative complication rate, postoperative hospital stay, 30-day mortality); (2) oncological outcomes (objective response rate, major pathological response [MPR], lymph node downstaging rate); and (3) prognostic indicators (disease-free survival [DFS]/progression-free survival [PFS], overall survival [OS]). Kaplan-Meier and Cox proportional hazard models were used to assess survival outcomes.

A total of 66 patients were included, with 38 undergoing conversion surgery and 28 continuing systemic therapy. Baseline characteristics were comparable between groups. Among surgical patients, 92.1% underwent lobectomy and 7.9% bilobectomy, all via video-assisted thoracoscopic surgery (VATS) without open conversion. The R0 resection rate was 97.4%, with a median postoperative hospital stay of 5 days and no 30-day mortality. Postoperative complications occurred in 5.3% of patients and were managed conservatively. MPR was achieved in 28.9% of patients, with a higher rate in those receiving EGFR-TKI plus chemotherapy (36.4% vs. 25.9%). T and N downstaging occurred in 78.9% and 57.9% of patients, respectively. The objective response rate in the surgical group exceeded 50%. After a median follow-up of 31.5 months, the surgery group demonstrated significantly longer DFS than the non-surgical group (48.0 vs. 15.1 months, P=0.009). Multivariate Cox analysis identified conversion surgery as an independent protective factor for both DFS and OS (P<0.05). At follow-up, 36 of 38 surgical patients were alive, with 19 experiencing distant recurrence (lungs, brain, bone, lymph nodes).

This study demonstrates that EGFR-TKI induction therapy provides effective tumor and nodal downstaging, enabling surgical resection in a subset of initially unresectable EGFR-mutant NSCLC patients. Conversion surgery was associated with favorable safety outcomes, minimal postoperative complications, and excellent recovery. Compared to systemic therapy alone, conversion surgery significantly improved DFS and OS, indicating its potential survival benefit. Multivariate analysis further supported surgery as an independent prognostic factor. These findings suggest that EGFR-TKI induction therapy combined with timely surgical intervention represents a promising treatment pathway with potential for long-term survival. Prospective, large-scale, multi-center studies are warranted to validate these results and refine treatment strategies for this patient population.