Single Institution Experience Using Circulating Tumor DNA to Monitor Recurrence in Rectal Cancer

BACKGROUND: Standard of care for locally advanced rectal cancers includes total neoadjuvant therapy followed by surgery or non-operative management based on response. There remains significant risk of both local and distant recurrence, despite close surveillance. The use of circulating tumor DNA in rectal cancer surveillance has not yet been standardized. OBJECTIVE: To assess the utility of circulating tumor DNA as an adjunct to surveillance for recurrence following definitive therapy. DESIGN: Single institution retrospective review. SETTINGS: Single National Cancer Institute designated and National Accreditation Program for Rectal Cancer accredited institution. PATIENTS: All patients diagnosed with rectal cancer from 2021-2024 with circulating tumor DNA data available. MAIN OUTCOME MEASURES: Circulating tumor DNA status at the time of clinical recurrence. Subgroup analysis of recurrence location. RESULTS: A total of 241 patients were diagnosed with rectal cancer between 2021-2024. Circulating tumor DNA data was available for 144/241 (59.8%). 28 patients with clinical recurrences were studied, 20 (71.4%) occurred after surgery and 8 (28.6%) during watch and wait. 20/28 (71.4%) recurrences had a positive circulating tumor DNA prior to detection of recurrence clinically. Circulating tumor DNA was positive a median of 100 days (range, 10-532 days) prior to recurrence being detected. 11/12 (91.7%) distant recurrences were circulating tumor DNA positive, compared to 10/17 (58.8%) local recurrences. LIMITATIONS: Retrospective single institution study with limited sample size. CONCLUSIONS: Circulating tumor DNA can be an asset during surveillance in both patients undergoing watch and wait or surgery, with identification of recurrences earlier than traditional methods. Within our study, a positive circulating tumor DNA was suggestive of distant metastases rather than local recurrence, which may impact decision making in the way we manage these patients, particularly when considering salvage surgery. Large prospective studies are needed to determine the ideal implementation of circulating tumor DNA into surveillance protocols. (See Video Abstract).