To determine if the detection of ctDNA after surgical resection of CLM can stratify patients into high and low-risk cohorts for early disease recurrence in order to inform post-operative adjuvant therapy.

Primary Objective:

• To assess 1-year recurrence-free survival rate following liver resection of CLM with curative intent among ctDNA-negative patients who receive risk-stratified postoperative chemotherapy

Secondary Objectives:

• To assess recurrence-free survival following liver resection of CLM with curative intent among ctDNA-positive patients
• To assess overall survival following liver resection among ctDNA-negative and ctDNA-positive patients
• To evaluate the proportion of ctDNA-negative at 1-year post-resection
• To compare survival of ctDNA-negative patients undergoing ctDNA-guided postoperative chemotherapy to historical controls
• To evaluate proportion of patients in each arm who change chemotherapy in response to ctDNA measurement
• To delineate the pattern of disease recurrence
• To assess ctDNA sensitivity and specificity for predicting disease recurrence
• To evaluate MDASI-GI during the course of postoperative therapy
• To evaluate and correlate patient molecular subtypes and characterization of tumor biologic factors that are associated with ctDNA detection
• To evaluate surgery-related adverse events occurring up to 90 days after surgery, and chemo-related adverse events occurring up to 30 days after the last dose of chemotherapy

Outcome Measures:

Primary:

• Recurrence-free survival at 1-year post-hepatectomy among ctDNA-negative patients

Secondary:

• Recurrence-free survival at 1-year post-hepatectomy among ctDNA-positive patients
• Overall survival (OS) among ctDNA-negative and ctDNA-positive patients
• ctDNA-negativity at 1-year post-resection
• Proportion of patients in each group with chemotherapy regimen change in response to ctDNA dynamics
• Pattern of disease recurrence (i.e., liver, systemic, salvageable vs. unsalvageable)
• ctDNA sensitivity/specificity for recurrent disease overall by timepoint
• MDASI-GI at clinic visits during course of postoperative therapy
• Tumor radiologic, histologic, and molecular profiling and correlative characterization based upon ctDNA detection
• Adverse events

Inclusion Criteria:

• Patients ≥18 years of age with CLM undergoing elective hepatectomy with curative intent (primary colorectal primary cancer previously removed OR being removed at time of hepatectomy) after preoperative chemotherapy (i.e., FOLFOX/FOLFIRI +/- bevacizumab or panitumumab/cetuximab) from 07/01/2021 - 12/31/2023
• Must receive ≥ 4 cycles of preoperative chemotherapy

Exclusion Criteria:

• Patients with primary colorectal tumor that will remain in situ
• Inability to undergo postoperative chemotherapy, or postoperative chemotherapy not planned a priori
• Unwilling/unable to undergo blood draws for ctDNA, patient or provider-determined
• Other active malignancies requiring treatment
• Women who are pregnant