3609 Background: Detection of circulating tumor DNA (ctDNA) is prognostic for recurrence after completion of curative-intent therapy for patients (pts) with colorectal cancer (CRC). Our MD Anderson INTERCEPT platform enrolls ctDNA(+) CRC pts onto matched clinical trials, with the goal of eradicating minimal residual disease (MRD) and curing more pts with CRC. To gain insights on how to identify CRC pts most likely to have true MRD, we retrospectively reviewed the role of non-specific radiographic abnormalities in forecasting CRC recurrence. Methods: For this retrospective review of CRC pts included in ctDNA intervention trials (Table) from 1/2019-12/2025, MRD at baseline was defined as (1) having no radiographically evident disease at time of study enrollment and (2) detection of ctDNA on an MRD assay (Signatera). ctDNA levels were quantified as mean tumor molecules (MTM) per mililiter (mL) plasma. Radiographic sites of disease progression on clinical trials were compared with pre-treatment imaging. Median recurrence-free survival (RFS) was estimated using Kaplan Meier and compared with Cox regression. Results: 54 pts with definitively treated CRC prior to subsequent ctDNA(+) were enrolled across 4 trials (Table); 45 pts (83%) had stage IV disease. No pts had radiographically evident CRC at trial start. Median ctDNA levels were 0.45 MTM/mL (IQR 0.12 – 2.4). After a median follow up of 6.4 months (IQR, 3.5-9.5), 42 (78%) pts had recurred after treatment on a ctDNA intervention trial. Median RFS was 8.1 months (95% CI 4.4 - 9.4). Sites of recurrence were liver (N=20, 48%), lung (N=13, 31%), lymph nodes (N=10, 24%), and peritoneum (N=3, 7%). Upon retrospective review, minute but discernible lesions were identified at the sites of recurrence in 25 (60%) of the pts who had a recurrence on MRD trials. At eligibility evaluation these were characterized as “benign” in 14 (56%) or as “post-procedural” in 11 (44%) of the cases. The presence of indistinguishable CRC deposits at the start of the trial was associated with inferior RFS (4.2 vs 9.3 months; HR 1.96 (95% CI 1.04-3.70; p = 0.04). Conclusions: Subclinical radiographic findings may confound true identification of pts with CRC MRD for clinical trials. Optimizing definitions of radiographically detectable disease is warranted in order to ensure homogenous populations of CRC that are the most likely to benefit from novel MRD therapies. Demographic characteristics across four trials. Number of Patients Percentage (%) Age at Enrollment < 30 1 2.4 30-39 3 7.3 40-49 8 19.5 50-59 12 29.3 60-69 14 34.1 70+ 3 7.3 Gender Male 34 63.0 Female 20 37.0 Race/Ethnicity White or Caucasian 34 63.0 Black or African American 5 9.3 Hispanic or Latino 11 20.4 Asian 1 1.9 Other 3 5.6 Stage at Enrollment I 0 0.0 II 0 0.0
Shekhar et al. (Wed,) studied this question.