Positive circulating tumor DNA (ctDNA) was highly prognostic of disease-free survival (DFS) within molecular residual disease (MLD) and surveillance windows for a subset of patients with stage II to III colorectal cancer enrolled in the BESPOKE CRC study.

These results were first presented by Purvi Shah, MD, MBBS, Virginia Cancer Institute, Richmond, Virginia, at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.

The BESPOKE CRC study was a multicenter, prospective, observation evaluation of the clinical utility of ctDNA for detecting the MRD-based early recurrence among patients with surgically resected colorectal cancer. From the patients enrolled, there were complete clinical and laboratory data available for 1001. The ctDNA testing was done with a clinically validated, personalized, tumor-informed multiplex PCR-next generation sequencing assay. The primary end point was impact of ctDNA testing on treatment decisions and asymptomatic recurrence rates, and secondary end points included MRD clearance rate, survival of MRD-negative patients, overall survival, and patient-reported outcomes. As part of an exploratory analysis, the correlation between ctDNA status and DFS was evaluated.

Following the curative resection, 62.4% of patients received adjuvant chemotherapy. The median follow-up duration was 23.15 months. Among those patients with ctDNA results available during the MRD window, ctDNA positivity was found in 8.1% of patients with stage II disease and 24.9% of patients with stage III. There was a significant association between ctDNA positivity and inferior DFS for both patients with stage II (hazard ratio [HR], 10.4; P < .0001) and stage III (HR, 10.1; P < .0001). For patients who tested ctDNA positive during the surveillance period, in both the cohort who underwent observation and those who underwent adjuvant chemotherapy, ctDNA-positivity had a correlation with significantly worse DFS. Dr Shah noted that ctDNA “demonstrated high sensitivity in detecting recurrence,” as well as “a high rate of potentially curative metastasis-directed therapy.” He added that the benefit of adjuvant chemotherapy was seen “exclusively” among patients with positive MRD.

Dr Shah et al concluded, “Our results highlight the potential value of ctDNA-based MRD detection for treatment-decision making.”

Source:

Shah P, Aushev V, Ensor J, et al. Circulating tumor DNA for detection of molecular residual disease (MRD) in patients (pts) with stage II/III colorectal cancer (CRC): Final analysis of the BESPOKE CRC sub-cohort. Presented at 2025 Gastrointestinal Cancers Symposium. January 23-25, 2025; San Francisco, CA. Abstract 15.