This is a single-center randomized trial that investigates microwave ablation (MWA) combined with EGFR-TKI therapy in 120 early-stage NSCLC patients (T1-T2N0M0, EGFR-mutant) unsuitable for standard treatments. Participants are stratified by tumor characteristics and randomized equally to MWA alone, MWA-TKI concurrent, or TKI induction followed by MWA-TKI, assessing disease-free survival, overall survival, and safety outcomes. The study compares the clinical benefits and optimal sequencing of local ablation with targeted therapy in early-stage EGFR-mutant NSCLC management.

This is a single-center, randomized, controlled, exploratory study enrolling patients with mixed ground-glass or solid lesions on CT, histologically or cytologically confirmed as NSCLC, harboring EGFR mutations, and clinically staged as Ia, Ib, or IIa (size ≤5 cm, T1-T2N0M0). Patients deemed unsuitable for or refusing surgery/radiotherapy after multidisciplinary assessment were included. Eligible participants who provided informed consent were randomized in a 1:1:1 ratio into three groups: microwave ablation alone (MWA), MWA combined with targeted therapy (MWA-TKI), or targeted therapy induction followed by MWA combined with targeted therapy (TKI-MWA-TKI). Randomization was stratified by solid tumor proportion (<50% vs ≥50%), tumor size (8-30 mm vs >30 mm), and EGFR mutation status (Ex19del vs Ex21 L858R). The study aims to enroll 120 participants. The primary endpoints include disease-free survival (DFS), overall survival (OS), and the incidence of adverse events. The study evaluates the efficacy, safety, and clinical benefits of MWA combined with EGFR-TKI therapy in early-stage NSCLC, comparing different treatment sequences.

Inclusion Criteria:

• CT findings showing mixed ground-glass or solid lesions, histologically or cytologically confirmed as NSCLC, with clinical stages Ia, Ib, or IIa (size ≤5 cm, T1-T2N0M0) according to the 9th edition of TNM classification.
• EGFR exon 19 deletion or exon 21 L858R mutation.
• Age ≥18 years.
• ECOG PS score of 0-2.
• Expected survival ≥3 months.
• Deemed unsuitable for or refusal of surgery/radiotherapy after multidisciplinary discussion.
• No prior EGFR-TKI targeted therapy.
• Willing to undergo initial ablation therapy, with good compliance to examinations and follow-ups, and able to understand the study and provide informed consent.

Exclusion Criteria:

• Severe liver, kidney, heart, lung, or brain dysfunction or other comorbidities that preclude tolerance to MWA or targeted therapy.
• Chest CT findings indicating percutaneous inaccessibility of the lung lesion for MWA.
• Platelet count <50×10⁹/L, severe bleeding tendency, or uncorrectable coagulation disorders.
• Current or prior (within 3 months) use of anti-tumor drugs or EGFR-TKI therapy.
• Uncontrolled conditions (including but not limited to non-pulmonary malignancies, active infections, symptomatic congestive heart failure, unstable angina, arrhythmias, psychiatric disorders, etc.).
• Pregnant or breastfeeding women, or those planning pregnancy during the study.
• Other conditions deemed by the investigator as unsuitable for study participation.