EP676 - Single Institution Experience Using Circulating Tumor DNA to Monitor Recurrence in Rectal Cancer

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Purpose/Background: Total neoadjuvant therapy (TNT) has become the cornerstone of treatment for locally advanced rectal cancers. With the increase in TNT has followed an increase in complete clinical response (cCR) and utilization of watch and wait (w&w) organ preservation management. In both w&w patients and patients who undergo surgery following TNT, there is still a significant risk of recurrence, making strict surveillance of paramount importance. The use of circulating tumor DNA (ctDNA), a biomarker that quantifies fragmented DNA shed by a tumor, has been used for monitoring treatment response and surveillance in multiple cancers. The purpose of this study was to assess the utility of using ctDNA surveillance in identifying patients at risk of regrowth or distant recurrence following TNT in rectal cancer.

Methods/Interventions: We performed a retrospective review within a single NCI-designated hospital with a nationally accredited rectal cancer program. All patients diagnosed with rectal cancer from 2021-2024 were included. Patients with mid or low locally advanced rectal cancers were recommended TNT after review at a multidisciplinary tumor board. In 2021 we began using ctDNA to test for minimal residual disease (MRD), and for surveillance following surgery or during w&w. Patients were recommended to have ctDNA drawn at completion of TNT (start of w&w) or within two weeks after surgery (MRD). Repeat draws were performed every three months. If a patient’s ctDNA turned positive, their lab cadence was increased to monthly.

Results/Outcomes: 105 patients were diagnosed with locally advanced mid to low rectal cancers and underwent TNT. CtDNA values were available for 56/105 (53.3%) of these patients. 21/56 (37.5%) patients had a cCR or near complete response and were recommended w&w, while 31/56 (55.4%) underwent surgery. 19/56 (33.9%) patients had a clinical recurrence (10 after surgery, 9 after w&w). 12/19 (63.2%) of these patients had ctDNA data available at the time of recurrence.

6/12 (50%) recurrences were participating in w&w. 5/6 (83.3%) w&w recurrences were local regrowth, with 3/5 (60%) ctDNA positive at the time of recurrence. 6/12 (50%) patients underwent TNT followed by surgery and then developed a recurrence (2 local, 4 distant). 100% of these had a positive ctDNA with their recurrence.

Of the 13 total recurrences (one patient recurred twice), 10/13 (76.9%) had a positive ctDNA prior to the detection of the recurrence clinically (imaging, endoscopy, biopsy). CtDNA was positive a median of 71 days (range 10-231 days) before recurrence was detected. This median is likely underestimated because for 3/10 (30%) positive patients this was their first CtDNA value. 3/13 (23.1%) recurrences had a negative CtDNA at the time the recurrence was detected. For 2/13 (15.4%) recurrences the ctDNA never turned positive. 1/13 (7.7%) recurrences the ctDNA turned positive 22 days after the recurrence was detected by other means.

Conclusion/Discussion: The best utilization of ctDNA in surveillance and management of rectal cancer is not well defined. Our data shows that ctDNA can be an asset in both patients undergoing w&w or surgery following TNT, with identification of recurrences earlier than traditional methods. Overall, many questions remain regarding the appropriate implementation of ctDNA into surveillance protocols. More studies with structured ctDNA surveillance protocols and larger patient populations are needed to determine the ideal frequency of ctDNA surveillance and the appropriate response to ctDNA positivity without evidence of recurrence.