Overview

This study is a prospective single-arm clinical trial targeting patients with stage IB-IIIA non-small cell lung cancer (NSCLC) who have received neoadjuvant immunotherapy. The primary objective is to evaluate whether a personalized follow-up and adjuvant treatment strategy-based on the combination of ctDNA-based minimal residual disease (MRD) testing and pathological response-can effectively improve the 2-year postoperative recurrence-free survival (RFS). The study will enroll 100 patients scheduled for radical surgery who have undergone neoadjuvant immunotherapy (in combination with platinum-based chemotherapy). Patients will receive individualized follow-up and adjuvant therapy based on dynamic changes in ctDNA at various preoperative and postoperative timepoints, as well as pathological response. Adjuvant therapy will be recommended if patients do not achieve pathological complete response (pCR) after surgery, or if ctDNA testing is positive after neoadjuvant therapy or post-surgery. Only patients who achieve pCR and have negative ctDNA at both specified timepoints will forgo adjuvant therapy; these patients will undergo blood sampling at each routine follow-up, with adjuvant therapy initiated upon ctDNA seroconversion to positive. The primary endpoint is 2-year RFS after surgery; secondary endpoints include overall survival (OS) and the diagnostic rate of recurrence/metastasis based on ctDNA-MRD testing. This project aims to explore the refinement of adaptive treatment strategies in the neoadjuvant immunotherapy lung cancer population, with the ultimate goal of improving overall therapeutic efficacy and establishing a standardized, integrated postoperative management system suitable for lung cancer patients.

Eligibility

Inclusion Criteria:

1. Signed written informed consent.
2. Male or female, aged ≥ 18 and \< 85 years.
3. Radical resection performed, pathologic stage IB-IIIA (8th TNM) non-small-cell lung cancer.
4. Tumor tissue and blood samples obtainable at all protocol-specified time-points.
5. No pure ground-glass nodule on imaging.
6. Completed standard neoadjuvant immunotherapy combined with platinum-based chemotherapy.

Exclusion Criteria:

1. Postoperative pathology shows other than NSCLC, including but not limited to benign lesions, small-cell carcinoma, metastasis, or indeterminate/inadequate histology.
2. Insufficient or poor-quality blood or tissue samples.
3. Pure ground-glass nodule on imaging.
4. History of any malignancy within the past 5 years.
5. Contraindication to surgery preventing radical resection.
6. Non-radical (R2) resection.
7. Pathologic stage IIIB-N3, IIIC, or IV on paraffin sections.
8. Refusal or withdrawal of informed consent.
9. Any condition deemed unsuitable by the investigator (e.g., perioperative blood transfusion, severe psychiatric disorder precluding follow-up).