Early risk stratification and assessment of adjuvant chemotherapy (ACT) efficacy for localized colorectal cancer (CRC) are still lacking in a large patient cohort with a fast and cost-effective approach. A recent prospective, multicenter study published in the Journal of Hematology and Oncology, led by the research team from Sun Yat-Sen University Cancer Centre, Shanghai Medical College of Fudan University, the Second Affiliated Hospital of Zhejiang University School of Medicine, and Nanjing Geneseeq Technology Inc., demonstrates that minimal residual disease (MRD) detection through circulating tumor DNA (ctDNA) evaluation using GeneseeqPrimeTM gene panel at as early as one week postoperatively could facilitate recurrence risk stratification and decision-making in postsurgical management.

This study recruited 276 stage II/III resectable CRC patients from 2017 to 2020, which is so far the largest cohort in published studies. Tumor tissue was collected at surgery, and serial blood samples were collected preoperatively within 1 week, postoperatively at 1 week, 6 months after surgery, and every 3 months thereafter for up to two years. All samples were analyzed using the GeneseeqPrimeTM 425-gene panel for targeted next-generation sequencing. Patients were treated and followed up per standard of care blindly to the MRD detection results.

Strikingly, ctDNA evaluation at as early as one week postoperatively was able to stratify patients with ctDNA detection who had remarkably high recurrence risk (hazard ratio [HR], 10.98, p<0.001). Likewise, at the first sampling time point after ACT, ctDNA-positive patients were ~12 times more likely to experience recurrence (HR=12.76, p<0.001). During surveillance after definitive therapy, ctDNA detection was also associated with extremely high recurrence risk (HR=32.02, p<0.001). Serial ctDNA analyses identified recurrence with a sensitivity of 83% and specificity of 94%, outperformed all other known clinicopathological risk factors, and could detect disease recurrence ahead of radiological imaging confirmation with a mean lead time of 5 months. In addition, dynamic ctDNA change provides a real-time indication of ACT efficacy.

“ctDNA evaluation in early postoperative phase during hospitalization would provide timely estimation of patient’s recurrence risk and potentially facilitate decision-making of ACT for high-risk patients”, says Dr. Hua Bao, author and the Director of Research & Development at Geneseeq.

Geneseeq announced CALIBRATETM, the MRD monitoring program using liquid biopsy in 2017. SHIELDINGTM, launched in early 2021, is Geneseeq’s first commercially available MRD product in China for clinical use in the management of early and mid-stage solid tumors. The focus of the CALIBRATETM program has expanded beyond CRC patients with additional data on other cancer types to follow.