E221: Pre-operative liquid biopsy for optimal patient selection in metastatic colorectal cancer: techniques to avoid futile liver resections

Futile liver resection (i.e. recurrence at ≤9 months) for metastatic colorectal cancer (mCRC) portends a poor overall survival. In this pilot study, we sought to determine if preoperative circulating tumor DNA (ctDNA) could be a useful predictor of futile liver resections, recurrence, and optimal chemotherapy duration following resection in patients with resectable liver mCRC.

Methods: Patients who underwent operative management for colorectal liver metastases from July of 2021 through January of 2023 were enrolled and evaluated with ctDNA pre-operatively and post-operatively at 6 weeks and 3, 6, 9, and 12 months for detection of recurrence.

Results: Eighty-five patients were screened for inclusion: 26 (31%) underwent any surgical procedure, while 21 (25%) underwent liver-specific surgical procedures and were included in the final analysis with a median age of 55 years [IQR 49, 63] and median follow-up time of 14.5 months [13, 18]. Sixteen patients (76%) had synchronous metastases at time of colorectal cancer diagnosis and 17 (81%) had liver only metastases with 7 (33%) having bilobar liver disease.  The median pre-operative ctDNA level was 0.46 MTM/ml [0.04, 32.65].  Ten (53%) patients with a pre-op ctDNA measurement recurred at or within 9 months of surgery. The median change in ctDNA level pre‑ to post-op was -0.05 [‑11.22, 0.01].  On univariate analysis among patients who recurred, the pre-op ctDNA level, change between pre‑op and post‑op ctDNA levels, and post-op ctDNA level did not correlate with time to recurrence. When pre-op ctDNA levels were separated into a dichotomous variable, detected vs undetectable, and compared with recurrence status, those with a detectable pre-op ctDNA level were more likely to recur (p = 0.04). When pre-op ctDNA groups were compared against recurrence groups (no recurrence, recurrence in ≤9 months, and recurrence > 9 months) there was no statistically significant difference between the groups (p = 0.11). 

Conclusions: New technologies including use of ctDNA may help better predict which patients with colorectal liver metastases will undergo futile surgery. Our preliminary findings suggest that patients with detectable ctDNA prior to surgery are more likely to recur. Utilization of ctDNA in guiding operative management should be done in conjunction with high quality imaging and other serologic markers to determine which patients with colorectal liver metastases are likely to receive durable benefit from operative intervention.