Segmentectomy After Induction Therapy (SAINT)

Inclusion Criteria:

* Patients must have histologically confirmed non-small-cell lung cancer that is clinically staged as ≤ycT1cN0M0 (tumor size 3cm or less on greatest dimension measured by cross-sectional imaging) after receiving induction therapy.
* Patients may have received any regimen of neoadjuvant chemotherapy, neoadjuvant immunotherapy, or neoadjuvant chemoimmunotherapy.
* Patients must have the ability to understand and the willingness to sign a written informed consent document.
* Patients must be age ≥ 18 years.
* Patients must exhibit a/an ECOG (Eastern Cooperative Oncology Group) performance status of \<3.
* Patients must have adequate organ function as defined below: These are guidelines that may or should be modified based on protocol-specific or drug development-specific needs.

Table 1: Measures of Adequate Organ Function. FEV1 or DLCO ≥40% (DLCO: diffusing capacity of lung for carbon monoxide)

* For patients with a known history of Human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 6 months prior to registration.
* For patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be considered a candidate for surgical resection under general anesthesia.
* Females of child-bearing potential (FOCBP) must have a negative pregnancy test prior to registration on study.

NOTE: A FOCBP is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

* Has not undergone a hysterectomy or bilateral oophorectomy
* Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for \> 12 months)

Exclusion Criteria:

* Patients who have had prior lung resection or thoracic surgery.
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
* Patients who are receiving any other investigational agents.
* Patients with evidence of distant metastases including brain metastases will be excluded from this study because they will not benefit from surgical resection.
* Patients that do not have documented consensus agreement on the feasibility of anatomic sublobar resection (segmentectomy) from at least 2 study surgeons will not be enrolled.
* Patients with pre-induction therapy tumor involving greater than 1 lobe.
* Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:

  * Hypertension that is not controlled on medication
  * Ongoing or active infection requiring systemic treatment
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * Psychiatric illness/social situations that would limit compliance with study requirements
  * Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
* Female patients who are pregnant. Pregnant patients are excluded from this study because the study protocol requires frequent cross-sectional imaging with potential for teratogenic effects.
* Patients with another malignancy within 3 years (except for non-melanoma skin cancer, CIS of cervix (a preinvasive carcinomatous change of the cervix), superficial bladder cancer). Patients with prior malignancies are excluded to isolate overall survival outcomes.
* Patients with active smoking status or cessation \<4 weeks prior to surgical resection.
* Patients with biopsy positive hilar or mediastinal lymph nodes following induction therapy detected by EBUS (endobronchial ultrasound), mediastinoscopy, or intraoperative sampling.