Circulating Tumor DNA Predicts Early Recurrence Following Locoregional Therapy for Oligometastatic Colorectal Cancer

Simple Summary: Colorectal cancer is a major cause of cancer death, often due to metastasis. For patients with limited spread, treatments to remove all cancerous lesions can extend life or even cure the disease. However, predicting who benefits most from further treatment is challenging. This study used tumor-informed circulating tumor DNA (ctDNA) testing to detect minimal residual disease (MRD) after locoregional therapy for metastatic colorectal cancer. The results showed that positive ctDNA results after curative-intent treatment predict poor prognosis better than traditional tests. Those with negative ctDNA had over three times longer survival without recurrence compared to those with positive ctDNA. In this group of patients, the majority of whom had received prior chemotherapy, receiving more of the same chemotherapy did not seem to delay cancer recurrence. These preliminary results set the stage for future prospective trials which may examine the value of ctDNA-guided patient management for those with colorectal cancer and limited metastatic disease. (1) Background: Local therapies offer a potentially curative approach for patients with oligometastatic colorectal cancer (CRC). An evidence-based consensus recommendation for systemic therapy following definitive locoregional therapy is lacking. Tumor-informed circulating tumor DNA (ctDNA) might provide information to help guide management in this setting. (2) Methods: A multi-institutional retrospective study was conducted, including patients with CRC that underwent curative-intent locoregional therapy to an isolated site of metastatic disease, followed by tumor-informed ctDNA assessment. The Kaplan-Meier method and log-rank tests were used to compare disease-free survival based on ctDNA results. ctDNA test performance was compared to carcinoembryonic antigen (CEA) test results using McNemar's test. (3) Results: Our study cohort consisted of 87 patients treated with locoregional interventions who underwent ctDNA testing. The initial ctDNA test post-intervention was positive in 28 patients and negative in 59 patients. The median follow-up time was 14.0 months. Detectable ctDNA post-intervention was significantly associated with early disease recurrence, with a median disease-free survival (DFS) of 6.63 months compared to 21.30 months in ctDNA-negative patients (p < 0.001). ctDNA detected a numerically higher proportion of recurrences than CEA (p < 0.097). Post-intervention systemic therapy was not associated with improved DFS (p = 0.745). (4) Conclusions: ctDNA results are prognostically important in oligometastatic CRC, and further prospective studies are urgently needed to define its role in guiding clinical decisions.