The SCIENCE trial is a multicenter, open-label, randomized, parallel, noninferiority investigator-initiated trial (IIT). This study aims to evaluate the prognostic differences between selective mediastinal lymph node sampling and systematic mediastinal lymph node dissection in patients with node-negative stage IIA to IIIB (N2) non-small-cell lung cancer (NSCLC) undergoing anatomical lobectomy following neoadjuvant chemoimmunotherapy.

Inclusion Criteria:

1. Voluntary participation with a signed written informed consent form.

2. Aged ≥ 18 and < 75 years, of either gender.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

4. Anticipated life expectancy of ≥ 12 months.

5. Histologically or pathologically confirmed peripheral non-small cell lung cancer (NSCLC), with clinical tumor, node, metastasis(TNM) stage IIA-IIIB, which according to the International Association for the Study of Lung Cancer(IASLC) 9th edition, and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

6. Absence of satellite nodules involving different lung lobes.

7. No history of prior ipsilateral thoracotomy.

8. Completion of neoadjuvant therapy prior to enrollment, consisting of a PD-1 inhibitor combined with platinum-based doublet chemotherapy.

9. Adequate organ function.

10. Cardiopulmonary function assessed by the investigator as meeting surgical standards, specifically: forced expiratory volume in one second (FEV1) > 1.0 L or diffusing capacity of the lung for carbon monoxide (DLCO) > 40% of the predicted value; and no other cardiopulmonary impairments that, in the investigator's judgment, would preclude surgery.

11. Evaluation by a multidisciplinary team (MDT) or an evaluation committee* confirming that R0 resection can be achieved via anatomical lobectomy.

    • Evaluation Committee: Composed of multidisciplinary experts with at least 10 years of clinical experience. Each participant's eligibility is discussed and evaluated by at least two experts to reach a consensus; in the event of a disagreement, a third expert will be invited for assessment.

Exclusion Criteria:

1. Anticipated inability to tolerate an anatomical lobectomy;

2. Anticipated requirement for sleeve resection, pneumonectomy, or pulmonary autotransplantation to remove the affected lobe;

3. Prior thoracic radiotherapy before the initiation of surgical treatment;

4. History of allogeneic tissue or solid organ transplantation;

5. Diagnosis of an autoimmune disease within 3 months prior to surgery, or currently receiving long-term systemic corticosteroid therapy (at a dose >10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy;

6. History of or current non-infectious interstitial lung disease requiring corticosteroid therapy;

7. Presence of viral infectious diseases during the screening period:

   1. Seropositivity for human immunodeficiency virus (HIV);
   2. Active hepatitis B: positive for hepatitis B surface antigen (HBsAg) with an HBV-DNA viral load >500 IU/mL or >2000 copies/mL;
   3. Active hepatitis C: positive for hepatitis C virus (HCV) antibody with an HCV-RNA viral load above the upper limit of normal (ULN);

8. Poorly controlled hypertension despite medical therapy, defined as systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg (adjustment of antihypertensive medications is permitted prior to study initiation, provided that the average of the last three consecutive blood pressure readings taken prior to enrollment is ≤150/90 mmHg, with at least a 2-minute interval between each measurement);

9. Active infection requiring intravenous anti-infective therapy at the time of screening;

10. History of another malignancy within 3 years prior to providing informed consent, excluding cured basal cell carcinoma of the skin, carcinoma in situ of the cervix or breast, superficial bladder cancer, and localized prostate cancer. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, PSA <10 ng/mL) are eligible to enroll if they have received radical treatment or are under active surveillance with stable disease, regardless of prior treatment status;

11. Any condition that, in the investigator's judgment, might interfere with the interpretation of study results, compromise the participant's ability to complete the study, or render study participation contrary to the participant's best interests;

12. Pregnant, lactating, or planning to become pregnant; or having a positive serum pregnancy test within 7 days prior to the first study treatment;

13. Poor compliance, or unwilling or unable to adhere to the protocol-specified procedures.