Dr Weinberg on the Prognostic Use of ctDNA Testing in Resected CRC

Benjamin Adam Weinberg, MD, associate professor, medicine, Georgetown Lombardi Comprehensive Cancer Center, discusses the ability of circulating tumor DNA (ctDNA)–based minimal residual disease (MRD) detection to predict the benefit of adjuvant chemotherapy in patients with resected colorectal cancer (CRC).

ctDNA-based MRD testing has shown prognostic value for patients with resected CRC, Weinberg begins. With extended follow-up, an enriched dataset is emerging from the CIRCULATE-Japan GALAXY trial (UMIN000039205), aiding in more concrete conclusions regarding the role of ctDNA testing in this patient population, he says. CIRCULATE-Japan GALAXY was a large, prospective, observational trial conducted in Japan that used the Signatera ctDNA platform. This trial enrolled 5996 patients with various stages of CRC and showed that ctDNA status was prognostic across stages, according to Weinberg.

CIRCULATE-Japan GALAXY focused on ctDNA MRD status at the 4-week post-operative window, prior to the receipt of adjuvant chemotherapy. Patients with positive ctDNA results at this point have a poor prognosis but seem to derive the most benefit from adjuvant chemotherapy, Weinberg explains. In the extended follow-up analysis, 3 distinct patient groups emerged. One group consisted of patients with ctDNA-positive results, one-third of whom cleared ctDNA and maintained clearance, experiencing excellent outcomes with minimal instances of recurrence, he reports. The second group, slightly less than one-third of patients, achieved transient ctDNA clearance with chemotherapy, but their ctDNA levels later became positive, typically within 6 to 12 months of surgery. By 2 years, most patients in this group had disease recurrence, Weinberg says. The final group comprised patients whose ctDNA levels never cleared; approximately one-third of patients fall into this category and have the least favorable disease-free survival and overall survival outcomes, he notes.

A growing body of evidence underscores the value of ctDNA testing as a prognostic tool, Weinberg reiterates. However, results from prospective randomized trials are still needed to refine treatment strategies for these distinct patient populations, he emphasizes. The ctDNA-positive population derives the most substantial benefit from adjuvant chemotherapy, whereas ctDNA-negative patients derive little to no benefit from this treatment approach depending on their disease stage, he notes. The increased clinical use of ctDNA testing may help oncologists tailor adjuvant CRC therapy more effectively, he concludes.