Dr Kasi on the Potential Implications of ctDNA presence in Colorectal Cancer

Pashtoon Murtaza Kasi, MD, MS, oncologist, researcher, Weill Cornell Medicine, NewYork-Presbyterian Hospital, discusses insights into and significant findings from the observational BESPOKE CRC study (NCT04264702) investigating circulating tumor DNA (ctDNA) and the study’s implications for clinical practice in treating patients with colorectal (CRC) cancer. The research primarily focused on the role of ctDNA as a biomarker for recurrence-free or disease-free survival (DFS) in patients with CRC, emphasizing the distinct outcomes based on ctDNA statuses.

Kasi highlights the substantial variance in DFS between ctDNA-positive and ctDNA-negative patients. The study revealed that ctDNA-positive patients experienced a notably higher recurrence rate within 2 years compared with those who were ctDNA negative. Notably, the median DFS was not reached for the ctDNA-negative cohort, indicating that over 80% of these patients remained cancer-free nearly 2 years post-diagnosis, in stark contrast to the ctDNA-positive group where cancer recurrence was significantly more frequent and occurred sooner, Kasi says.

The research also delved into the prevalence of ctDNA positivity in the adjuvant minimal residual disease window, which typically spans the initial 2 to 12 weeks prior to the commencement of chemotherapy. Findings showed a disparity in ctDNA positivity between patients with stage II and stage III colon cancer, with a 6.43% positivity rate in those with stage II disease and a 21.87% positivity rate in those with stage III disease. These statistics are critical for stratifying patient risk and designing future oncological studies, Kasi emphasizes.

Furthermore, the study explored beyond the prognostic implications of ctDNA to determine whether ctDNA could also serve as a predictive marker for therapeutic outcomes. Data indicated that ctDNA-positive patients who underwent adjuvant chemotherapy experienced significantly improved DFS outcomes compared with those who did not receive such treatment, indicating that ctDNA status might inform treatment decisions. Specifically, it appears that converting from ctDNA-positive to ctDNA-negative status through treatment could yield substantial benefits.

Kasi also points out the ongoing research evaluating whether ctDNA-negative patients could safely forego the rigors of chemotherapy, thus avoiding its associated toxicities. This aspect of the study supports the hypothesis that ctDNA-negative status might predict lower recurrence risk and, consequently, lesser necessity for aggressive treatment regimens.

Kasi notes that these findings underscore the potential of ctDNA as a crucial biomarker in CRC management, influencing both the prognosis and treatment pathways. The study’s outcomes provide valuable data that could significantly refine the approach to chemotherapy use, emphasizing a more tailored treatment strategy based on individual ctDNA profiles, according to Kasi. This research undoubtedly contributes to the evolving landscape of personalized medicine in oncology, offering new avenues for both clinical trials and patient care, Kasi concludes.