New combo approach for Lung-Limited colorectal cancer shows promise in early trial

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Histological confirmation of colorectal adenocarcinoma * Metastatic colorectal cancer involving the lung classified as determined by the treating clinical team * Diagnosis of colorectal metastasis to lung made either histologically with trans-thoracic needle biopsy or clinically based on radiographic imaging * Identification as a medically appropriate candidate for surgical resection of the lung metastasis (metastases) according to the evaluating cardiothoracic surgeon. Standard justification for deeming a patient medically operable based on: * Pulmonary reserve adequate to tolerate complete resection of all intrathoracic disease, as deemed by thoracic surgeon, which may be determined by: * Baseline forced expiratory volume in one second (FEV1) \> 40% predicted * Post-operative predicted FEV1 \> 30% predicted * Diffusion capacity of the lung for carbon monoxide (DLCO) \> 40% predicted * Absent baseline hypoxemia and/or hypercapnia * Exercise oxygen consumption \> 50% predicted * Absent severe pulmonary hypertension * Absent severe cerebral, cardiac, or peripheral vascular disease * Absent severe chronic heart disease * Ability to tolerate surgical resection and acceptable operative risk as deemed by thoracic surgeon based on performance status and medical comorbidities * Identification as a medically appropriate candidate for systemic chemotherapy at the discretion of the evaluating medical oncologist * Resection/definitive therapy of primary colorectal tumor with no suspicion of recurrence. Prior radiation to a rectal adenocarcinoma is permitted * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Ability to provide informed consent for participation * Leukocytes \>= 2,000/mcL * Absolute neutrophil count \>= 1,000/mcL * Hemoglobin \>= 9.0 gm/dL * Platelet count \>= 100,000/mcL * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (except patients with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN * Serum creatinine =\< 1.5 x ULN OR creatinine clearance (CrCl \>= 50 mL/min (if using the Cockcroft-Gault formula) * Patients (men and women) of child bearing potential should use an effective (for them) method of birth control throughout their participation in this study Exclusion Criteria: * Tumor involvement at other metastatic sites (e.g., liver, distant lymph nodes) that has not been definitively treated. Prior surgical resection for metastatic disease at other (non-pulmonary) sites is permitted * Presence of intact primary colorectal adenocarcinoma (or of an anastomotic recurrence) * Previous radiotherapy to a lung metastasis that is still detectable radiographically * Known dihydropyrimidine dehydrogenase (DPD) deficiency that would preclude the patient from tolerating 5- fluorouracil chemotherapy * Prior intolerance of systemic therapies used as standard regimens in the treatment of metastatic CRC that would prohibit further receipt of systemic chemotherapy and/or biologic agents -e.g.,5-fluorouracil, oxaliplatin, irinotecan, anti-VEGF therapies (e.g., bevacizumab, ramucirumab), or anti-EGFR therapies (e.g., cetuximab, panitumumab, for patients with RAS wild-type colorectal tumors) * Prior therapy with regorafenib or trifluridine/tipiracil (TAS-102) for metastatic/unresectable colorectal cancer * Synchronous primary or prior malignancy in the past 5 years other than non-melanomatous skin cancer or in situ cancer * Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus