Adjuvant Therapy Confers Postoperative ctDNA Clearance, DFS Benefit in CRC

"ctDNA clearance is useful for seeing potential benefit in novel therapeutic studies," according to study author Emerik Osterlund, MD, PhD.

Adjuvant therapy can feasibly yield circulating tumor DNA (ctDNA) clearance in a portion of patients with colorectal cancer (CRC) and postoperative ctDNA positivity, with clearance correlating with superior disease-free survival (DFS) outcomes, according to findings from the INTERCEPT CRC study presented at the European Society for Medical Oncology (EMSO) Congress 2025.1

ctDNA dynamics data after the time of surgery or ablation revealed that 69% of patients had ctDNA negativity on all tests, while 18% had positive results on all tests. Additionally, 3.1% had ctDNA clearance on at least 2 tests, 2.4% had clearance on 1 test, and 8% converted from ctDNA negativity to positivity. Furthermore, adjuvant therapy resulted in ctDNA clearance among 26% (n = 20/77) of patients with ctDNA-positive results after surgery, with 13 (17%) having clearance on at least 2 tests.

From the time of first ctDNA-positive test result in the stage I to III CRC population, DFS outcomes were significantly improved among those with clearance on at least 2 tests (P <.0001). Data revealed similarly significant outcomes among patients with stage IV disease (P <.0001).

Following adjuvant therapy, 70% of patients had ctDNA negativity on all tests, while 19% had positive results on all tests. Other data showed that 1.5% had ctDNA negativity on at least 2 tests, 1.4% had clearance on 1 test, and 9% converted from ctDNA negativity to positivity.

The study population included 403 patients who had ctDNA-positive results at any time after surgery and adjuvant treatment, with 4.2% showing at least 1 subsequent negative reading without any intervention. Furthermore, 2.1% of this population had ctDNA-negative results on at least 2 sequential tests without any intervention, and 1.7% had no recurrences at the time of follow-up. Among patients with spontaneous ctDNA clearance, the median duration of clearance was 11.2 months, and the mean tumor molecules per milliliter was 0.06 (range, 0.02-1.89).

“Adjuvant treatment can clear a quarter of the patients [who] are ctDNA positive postoperatively. Those with ctDNA clearance had superior DFS,” presenting author Emerik Osterlund, MD, PhD, a postdoctoral fellow in Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, stated in the presentation.1 “The rate and durability of [spontaneous] ctDNA clearance was very low.”

According to Osterlund, previous studies have demonstrated how ctDNA can be employed to monitor minimal residual disease, with ctDNA positivity representing a strong risk factor for disease recurrence following procedures administered with curative intent.2 However, he noted limited findings on the rates and durability of spontaneous ctDNA clearance, the process of transitioning from ctDNA positivity to negativity without any intervention. Consequently, Osterlund and colleagues aimed to evaluate the behavior and clearance of ctDNA following procedures with curative intent among patients with stage I to IV CRC.

As part of the INTERCEPT program, 1301 patients with newly diagnosed or previously treated resectable stage I to IV CRC enrolled on the study, with 53% having stage I to III disease and 47% having stage IV disease. Patients received standard-of-care therapy—surgical resection with or without neoadjuvant and adjuvant treatment—and underwent tissue collection and testing via ctDNA assays in the postoperative setting and/or following therapy. Investigators then conducted routine surveillance via imaging & labs, with ctDNA assay testing occurring approximately every 3 months at each surveillance visit.

“ctDNA clearance is useful for seeing potential benefit in novel therapeutic studies,” Osterlund concluded.1

References

1. Osterlund E, Maddalena G, Pellatt AJ, et al. Circulating tumour DNA (ctDNA) clearance and correlation with outcome in the INTERCEPT colorectal cancer (CRC) study. Presented at the European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract 732MO.
2. Dasari A, Morris VK, Allegra CJ, et al. ctDNA applications and integration in colorectal cancer: an NCI Colon and Rectal-Anal Task Forces whitepaper. Nat Rev Clin Oncol. 2020;17(12):757-770. doi:10.1038/s41571-020-0392-0.