Minimal residual disease detection in colorectal cancer – Can ctDNA re-define adjuvant treatment?

Colorectal cancer remains a major cause of cancer-related death worldwide. The most substantial opportunity for improving colorectal cancer survival outcomes is in the setting of early stage disease, where evidence indicates that adjuvant chemotherapy can reduce recurrence and prevent cancer-related death through the eradication of minimal residual disease. However, the current treatment approach lacks precision and has quite a modest survival impact. A powerful prognostic marker could revolutionise adjuvant therapy by (i) better defining the recurrence risk of individual patients and allowing delivery of a more personalised treatment approach and (ii) enriching studies of new therapies with high risk patients, substantially reducing the size and cost of adjuvant therapy trials. Recent studies have demonstrated across multiple colorectal cancer patient cohorts that analysing for circulating tumour DNA (ctDNA) is directly testing for the presence of occult residual cancer and that repeat testing is a means of assessing the efficacy of adjuvant chemotherapy after curative intent treatment (1-4). These pivotal findings have led to the initiation of several randomised trials exploring the potential role of ctDNA-informed adjuvant therapy approach compared to standard of care treatment for patients with early stage colorectal.

References:

1. Tie J, Wang Y, Tomasetti C, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Science translational medicine. 2016;8(346):346ra92.
2. Tie J, Cohen JD, Wang Y, et al. Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study. Gut. 2018
3. Tie J, Cohen JD, Wang Y, et al. Serial circulating tumor DNA (ctDNA) analysis as a prognostic marker and a real-time indicator of adjuvant chemotherapy (CT) efficacy in stage III colon cancer (CC). J Clin Oncol (abstract ID 3516). 2018
4. Wang Y, Li L, Cohen J, et al. Prognostic potential of circulating tumor DNA in postoperative surveillance of non-metastatic colorectal cancer. JAMA Oncology. 2019 May 9.