Primary Tumor Resection Plus Osimertinib in Advanced EGFR-mutant Non-small Cell Lung Cancer

Inclusion Criteria:

1. Age 18-75 years, no restriction on sex.
2. Histologically or cytologically confirmed stage III-IV non-squamous NSCLC, unresectable as assessed by multidisciplinary team (MDT).
3. Presence of EGFR exon 19 deletion (19Del) or L858R mutation, confirmed by ARMS-PCR, NGS, or other validated methods.
4. No prior systemic therapy for lung cancer.
5. ECOG performance status of 0-1.
6. Estimated life expectancy of at least 6 months.
7. Primary lung tumor size ≥1 cm, with at least one measurable lesion remaining after resection according to RECIST v1.1 criteria.
8. Adequate organ function, including:

   ① Hematologic function: absolute neutrophil count ≥1.5 × 10⁹/L; platelet count ≥100 × 10⁹/L; hemoglobin ≥9.0 g/dL.

   ② Hepatic function: ALT and AST ≤2.5 × ULN (≤5 × ULN if liver metastases are present); total bilirubin ≤1.5 × ULN.

   ③ Renal function: serum creatinine ≤1.5 × ULN, or creatinine clearance ≥50 mL/min (Cockcroft-Gault formula).
9. Adequate pulmonary function (must meet at least one of the following to ensure postoperative reserve):

   ① FEV1 ≥1.2 L (or ≥40% of predicted value);

   ② FEV1/FVC ≥0.7, to exclude severe obstructive ventilatory dysfunction;

   ③ DLCO (diffusing capacity for carbon monoxide) ≥40% of predicted value, to assess diffusion capacity.

   ④ If preoperative FEV1 \<1.2 L or DLCO \<40%, additional cardiopulmonary exercise testing (e.g., 6-minute walk test, stair climbing test) is recommended to evaluate postoperative pulmonary reserve.
10. Evaluated by the study team and deemed suitable for primary tumor resection.
11. Signed written informed consent and willingness to comply with study protocol.

Exclusion Criteria:

1. Presence of any other known EGFR mutations.
2. Histological evidence of mixed small-cell lung cancer (SCLC) or history of transformation to SCLC.
3. Immunodeficiency: history of primary immunodeficiency disorders, or prior allogeneic organ or bone marrow transplantation.
4. Active brain metastases. Patients with adequately treated brain metastases may be eligible if they are neurologically stable for at least 2 weeks before enrollment, and are either not requiring corticosteroids or receiving a stable or decreasing dose of ≤10 mg prednisone (or equivalent) once daily.
5. Pregnancy.
6. Any serious comorbid condition that, in the opinion of the investigator, may interfere with participation in the study or interpretation of study results, including but not limited to: uncontrolled systemic diseases, psychiatric illness, active or uncontrolled infections, or other abnormal findings from laboratory or clinical examinations.