New Insights From IDEA-France & HORG: The Prognostic Power of ctDNA and Immunoscore

For patients with stage III colon cancer, immunoscore and circulating tumor DNA (ctDNA) are 2 biomarkers that can improve prognostication and tailor adjuvant treatments.

A recent post hoc analysis of the phase 3 IDEA-France and HORG trials has gleaned more information on the prognostic value of these 2 biomarkers in patients who took part in the trials.

In both randomized trials, plasma samples were collected after surgery and before adjuvant chemotherapy. A 16-plex protein chain reaction assay was used to analyze ctDNA. Multivariable analyses incorporating ctDNA, immunoscore, treatment duration, and disease risk group were conducted to evaluate time to recurrence (TTR)—measured from date of random assignment to first recurrence or colon cancer–related death, whichever came first—and overall survival (OS).

Among 554 patients with evaluable ctDNA results, 445 (80.3%) were ctDNA negative, and 109 (19.7%) were ctDNA positive. Patients with ctDNA positivity had a higher prevalence of aggressive disease features, including T4/N2 status and venous embolism, lymphatic invasion, and perineural invasion.

With a median follow-up of 6.7 years, the 2-year TTR rate was significantly lower in ctDNA-positive patients at 43.5% (95% CI, 34.1%-52.6%) compared with ctDNA-negative patients at 88.1% (95% CI, 84.7%-90.8%; P<0.001). Circulating tumor DNA was confirmed as an independent prognostic marker for both TTR (adjusted hazard ratio [adjHR], 5.21; 95% CI, 3.59-7.58; P<0.001) and OS (adjHR, 4.84; 95% CI, 3.40-6.89; P<0.001).

Circulating tumor DNA was the strongest independent prognostic marker for both TTR (adjHR, 5.21; 95% CI, 3.59-7.58; P<0.001) and OS (adjHR, 4.84; 95% CI, 3.40-6.89; P<0.001), regardless of disease stage, treatment duration, or immunoscore. Although immunoscore remained prognostic for ctDNA-negative patients, it had no significant impact for ctDNA-positive patients.

Data from the IDEA-France and HORG trials have demonstrated the efficacy of ctDNA as a major independent prognostic biomarker in patients with stage III colon cancer after surgery. Immunoscore can also supply additional prognostic information for patients who are ctDNA negative.