This clinical trial compares the effect of pulmonary vein-first surgical technique to pulmonary artery-first surgical technique in decreasing circulating tumor cell deoxyribonucleic acid (ctDNA) in patients with stage I-III non-small cell lung cancer. Pulmonary vein first and pulmonary artery first surgical techniques are standard surgical techniques for the division of the blood vessels during lung resection surgery. Pulmonary vein-first surgical technique may reduce the risk of shedding tumor cells during surgery and influence long term overall survival.

PRIMARY OBJECTIVE:

I. To determine the association between sequence of surgical resection and postoperative ctDNA levels at specified time points.

SECONDARY OBJECTIVE:

I. To determine the associated between sequence of surgical resection and postoperative ctDNA level and clinical oncologic outcomes.

II. To assess disease-free survival and the role of circulating tumor DNA in disease recurrence in patients with resectable non-small cell lung cancer.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients undergo pulmonary vein first approach surgical procedure on day of surgery.

GROUP II: Patients undergo pulmonary artery first approach surgical procedure on day of surgery.

After completion of surgery, patients are followed up at day 1, day 7, days 7-28, 4 months, every 6 months for 2 years, then every 6 months for up to 5 years

Inclusion Criteria:

• Any patients 18 years of age or older with confirmed or suspected early-stage (stage I-III) NSCLC
• Eligible and scheduled for surgical anatomic lung resection (e.g. lobectomy or segmentectomy) as routine clinical care for their disease

Exclusion Criteria:

• Previous cancer diagnosis within 5 years (except ductal carcinoma in situ [DCIS] of the breast, superficial bladder cancer, non-melanoma skin primary, other malignancy that does not require treatment).
• Preoperative chemotherapy, immunotherapy, or radiation therapy
• Receipt of perioperative blood transfusion