Presence of Postoperative ctDNA May Be Predictive of Recurrence Risk in Colorectal Cancer

As data on the potential of circulating tumor DNA (ctDNA) as a biomarker in several cancers mounts, a large multicenter study is indicating that the presence of postoperative ctDNA is highly predictive of relapse in patients with stage II-III colorectal cancer.

Results of the study showed that being positive for ctDNA 3 to 7 days following operation resulted in patients being nearly 11 times more likely to have disease recurrence. This increased risk remained even after adjuvant chemotherapy (ACT), with ctDNA-positive patients being 12 times more likely to have recurrence.

Based on the prognostic value observed in the study, the researchers suggest that evaluating ctDNA status as early as within a week of surgery could aid in risk stratification of patients and decision-making for postoperative management.

“It’s groundbreaking that, not like any other conventional factors for recurrence risk stratification (high versus low), detection of ctDNA is the reflection of MRD itself (yes versus no),” commented the researchers. “As the ctDNA measuring technology continues to evolve and manifest its significance, the real-time detection of MRD using ctDNA may help guide the precise administration of ACT, evaluation of ACT efficacy, and monitoring of disease recurrence.”

In contrast to the 20 patients who were positive for ctDNA and had a 2-year recurrence-free survival (RFS) rate of just under 40.0%, the 220 (91.7%) patients who were negative for ctDNA had a low recurrence risk, with a 2-year RFS rate of 89.4%.

The study also found that serial ctDNA detection identified recurrent disease before radiological imaging. According to the researchers, serial ctDNA analyses identified recurrent disease approximately 5 months ahead of radiological imaging and accurately identified recurrent disease 92% of the time.

“The results from 240 patients strongly support the notion that positive ctDNA status could reflect the existence of [minimal residual disease] and thus the extremely high risk of disease recurrence,” explained the researchers. “Across the whole clinical course, ctDNA status remained the most significant and independent predictor of RFS among all clinicopathological risk factors though the multivariate analysis may be not powered given the small subgroup size of ctDNA-positive patients, and the dynamic change of ctDNA status was in good concordance with clinical courses and outcomes.”

A subgroup analysis comparing patients who received ACT with patients who did not receive ACT showed that ctDNA was significantly associated with RFS in both groups, indicating that ctDNA’s association with RFS is independent of ACT use.

Reference

Chen G, Peng J, Xiao Q, et al. Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer. J Hematol Oncol. Published online May 17, 2021. doi:10.1186/s13045-021-01089-z