Circulating Tumor DNA (ctDNA) Testing Can Inform Treatment and Predict Outcomes in Colorectal Cancer

According to updated results from the BESPOKE CRC trial, circulating tumor DNA (ctDNA) testing can inform treatment decisions and predict outcomes of adjuvant chemotherapy in patients with stage II-III colorectal cancer. The results were presented at the ASCO Gastrointestinal Cancers Symposium 2025.

The BESPOKE CRC trial (NCT04264702) included 1,166 patients with surgically resected stage II-III colorectal cancer. At baseline, the patients’ median age was 61.8 years, 56.7% were men, and 55.7% had stage III disease. The patients underwent ctDNA testing at various time points.

Dr. Purvi K. Shah, from the Virginia Cancer Institute, explained:

"The first time point, called the MRD (molecular residual disease) time point, was collected 2-6 weeks after surgery. Subsequent collections occurred at 2, 4, and 6 months, and then every 3 months up to 24 months post-surgery. Oncologists received the results and treated patients at their discretion according to standard care guidelines."

A total of 694 patients received adjuvant chemotherapy, while 472 were placed under observation. Among oncologists, 83.7% reported that ctDNA testing did not influence their treatment decisions, but 83.8% stated that the results helped reinforce their treatment choices.

Among the 16.3% of oncologists whose treatment decisions were influenced by ctDNA testing:

• 35.7% intensified treatment.
• 59.9% reduced treatment intensity.

Researchers found that ctDNA positivity after surgery was associated with worse disease-free survival (DFS).

• In stage II patients, the 2-year DFS rate was 91.8% for ctDNA-negative patients, compared to 45.9% for ctDNA-positive patients (HR: 11.23; 95% CI: 6.43-19.62; P <.0001).
• In stage III patients, the 2-year DFS rate was 87.4% in ctDNA-negative patients and 35.5% in ctDNA-positive patients (HR: 8.33; 95% CI: 5.89-11.78; P <.0001).

Additionally, clearing ctDNA during and after adjuvant chemotherapy was associated with superior DFS.

• ctDNA clearance at 3 months significantly improved DFS (HR: 0.43; 95% CI: 0.29-0.64; P <.0001).
• ctDNA clearance at 6 months further improved DFS (HR: 0.31; 95% CI: 0.19-0.52; P <.0001).

Finally, researchers determined that ctDNA testing could predict the benefits of adjuvant chemotherapy.

• In ctDNA-positive patients, the 2-year DFS rate was 40.3% in those who received adjuvant chemotherapy vs. 24.7% in those under observation.
• In ctDNA-negative patients, the 2-year DFS rate was similar: 89.7% for those receiving chemotherapy and 89.5% for those under observation.

Dr. Shah concluded:

"This first U.S.-based prospective study demonstrated that post-operative ctDNA testing altered adjuvant management in 1 out of 6 patients and validated treatment plans for the majority. Serial ctDNA testing was linked to an increased rate of potentially curative metastasis-directed therapy. Moreover, ctDNA positivity was highly prognostic for DFS within MRD surveillance. Adjuvant chemotherapy benefits were exclusively observed in MRD-positive patients, and ctDNA clearance by months 3 and 6 was predictive of improved DFS."