Among a cohort of patients with stage II to IV colorectal cancer (CRC) who underwent curative-intent resection, the addition of serial circulating tumor DNA (ctDNA) testing provided limited clinical benefit. The retrospective, case cohort study aimed to examine the benefits of adding serial ctDNA assays for potential curative outcomes in patients with resected CRC. The cohort included patients who underwent ctDNA testing between September 20, 2019, and April 3, 2024. Surveillance protocols involved serial ctDNA testing every 3 months for 2 years, then every 6 months for the next 3 years. Reflex imaging, triggered by positive ctDNA results, was performed every 3 months until recurrence was confirmed. Recurrence was defined by positive imaging or ctDNA assays. The study population was divided into 4 cohorts based on ctDNA and imaging results, with additional stratification for those with reflex imaging.
The primary outcome was the proportion of patients benefiting from ctDNA testing, defined as cases where ctDNA positivity led to early imaging-based recurrence detection and subsequent curative-intent interventions without evidence of recurrence at data cutoff. A total of 184 patients were included, in which 45 had recurrent disease, 11 had recurrence with concurrently positive ctDNA and imaging findings, 14 had recurrence by imaging with a negative ctDNA assay, and 20 had a positive ctDNA-recurrence with negative imaging studies. Among the 45 patients evaluated, 20 experienced ctDNA positivity with negative imaging at the time of the first positive ctDNA result. Of these, 6 patients underwent reflex imaging, which confirmed recurrence, while the remaining 14 continued with serial imaging and ctDNA monitoring. Among the latter group, 10 patients were later diagnosed with recurrent disease, 3 experienced spontaneous ctDNA clearance without recurrence, and 1 remained imaging-negative for 7 months post-ctDNA positivity before being lost to follow-up. Overall, 11 of the 20 patients with ctDNA-detected recurrence without concurrent imaging findings underwent metastasectomy, but only 3 remained disease-free at the data cutoff in April 2024. This accounted for just 1.6% of the total surveilled population, highlighting the limited clinical benefit of ctDNA testing in this context.
This study has several limitations. Its retrospective design restricted the interpretation of findings, and the follow-up duration varied, with some patients only partially completing the surveillance schedule. This contributed to a low observed prevalence of disease recurrence. The small sample size may have underestimated the clinical impact of serial ctDNA testing. Additionally, patients without recurrence had not yet completed a full 5-year follow-up, potentially leading to an overestimation of clinical benefit.
Despite these limitations, the researchers believe the study finds limited clinical benefit of adding ctDNA assays to standard of care surveillance for patients with stage II to IV CRC. Future prospective trials are needed to evaluate whether the addition of ctDNA to surveillance improves relevant clinical outcomes, including patient-reported outcomes, over the standard of care and whether the frequency of testing is worth the cost and psychological impact on patients.
