NCCN Strengthens Guidance on ctDNA in Colon Cancer, Rectal Cancer, and Merkel Cell Carcinoma

The National Comprehensive Cancer Network (NCCN) has recently updated its guidelines to include circulating tumor DNA (ctDNA) as a prognostic marker for recurrence in the adjuvant setting for colon and rectal cancer. This recognition highlights the growing importance of ctDNA in cancer management and surveillance. The updated guidelines also provide a positive recommendation for ctDNA monitoring in surveillance for Merkel cell carcinoma (MCC), emphasizing its potential in assessing disease burden and predicting recurrence.

The NCCN's updated guidelines recognize the prognostic value of ctDNA in colon and rectal cancer, acknowledging its ability to provide additional recurrence risk information compared to other risk factors. However, the panel remains cautious about its use for surveillance and suggests that more clinical trials are needed to gather more data on the predictive value of ctDNA and other multigene assays for adjuvant treatment and surveillance strategies.

In the case of MCC, the updated NCCN guidelines state that ctDNA can assess disease burden in both virus-positive and virus-negative MCC and typically becomes positive prior to or at the time of a clinically evident recurrence. The guidelines recommend obtaining ctDNA tests every 3 months for surveillance, citing a prospective multicenter study published in the Journal of Clinical Oncology (JCO) that demonstrated excellent performance of Signatera, with 95% detection at time of enrollment and a 20x higher risk of recurrence among patients who were persistently Signatera positive.

The positive recommendation for ctDNA monitoring in MCC sets a precedent for the important role of ctDNA testing across other indications. As more data becomes available, ctDNA monitoring could become a standard component of surveillance and management strategies for various cancer types, including but not limited to colon, rectal, and other solid tumors.

In conclusion, the NCCN's updated guidelines on ctDNA in colon and rectal cancer, as well as its positive recommendation for ctDNA monitoring in MCC, reflect the growing recognition of ctDNA's prognostic value in cancer management and surveillance. As more clinical evidence becomes available, ctDNA may play an increasingly significant role in clinical practice, potentially complementing other prognostic and predictive markers such as multigene assays and Immunoscore. However, further research and clinical trials are needed to fully understand the predictive value of ctDNA and its optimal use in adjuvant treatment and surveillance strategies.