Signatera ctDNA in stage II CRC: A retrospective comparison with traditional risk factors for survival and prognostic stratification.

Abstract

e15641 Background: Stage II colorectal cancer (CRC) presents a clinical challenge due to variable recurrence risk and uncertain benefits of adjuvant chemotherapy. This study evaluates the prognostic value of Signatera circulating tumor DNA (ctDNA) analysis(a novel method for detecting minimal residual disease (MRD))against conventional high-risk clinicopathological features and tumor sidedness in predicting progression-free survival (PFS) and overall survival (OS). By comparing ctDNA’s predictive utility with established risk factors, the research aims to clarify its role in guiding treatment decisions and improving survival outcomes in stage II CRC. Methods: We analyzed 65 stage II CRC patients. Patients were stratified by initial Signatera ctDNA results (positive vs. negative), presence of high-risk features (T4 stage, lymphovascular invasion, or < 12 lymph node sampling, symptoms of bowel obstruction, perforation, age greater than 75 at presentation), and right vs left sided tumor location. The primary endpoint was 24-month PFS in ctDNA-negative patients (n = 57). Secondary endpoints included 24-month OS stratified by ctDNA status, adjuvant therapy impact, high-risk features, and tumor sidedness. Statistical analyses employed Kaplan-Meier estimates and Cox proportional hazards models. Results: The 24-month PFS rate was 93% (53/57) in ctDNA-negative patients. 24-month OS was 89%, with ctDNA-negative patients demonstrating superior OS (93%) compared to ctDNA-positive patients (63%; n = 8; HR: 3.2, 95% CI: 1.8–5.6, p < 0.001). High-risk features were associated with reduced PFS (HR: 2.1, 95% CI: 1.3–3.4, p = 0.002) and OS (HR: 2.5, 95% CI: 1.5–4.2, p < 0.001). Right-sided tumors exhibited inferior PFS (HR: 1.8, 95% CI: 1.1–2.9, p = 0.02) and OS (HR: 2.0, 95% CI: 1.2–3.3, p = 0.008) compared to left-sided tumors. Adjuvant chemotherapy was administered to 26 patients (40%), with no statistically significant survival differences between groups. Conclusions: Initial negative Signatera ctDNA results are strongly associated with favorable PFS in stage II CRC patients, while positive ctDNA, high-risk features, and right-sided tumor location are significant predictors of poor survival outcomes. These findings highlight the critical role of ctDNA analysis and tumor characteristics in refining risk stratification and guiding adjuvant therapy decisions for stage II CRC patients. These data should be looked alongside large randomized clinical trials prior to routine use of Sigatera ctDNA in clinical practice. Variable PFS HR (95% CI) OS HR (95% CI) ctDNA Positive vs. Negative 2.8 (1.6-4.9) 3.2 (1.8-5.6) High-Risk Features Present 2.1 (1.3-3.4) 2.5 (1.5-4.2) Right-Sided vs. Left-Sided 1.8 (1.1-2.9) 2.0 (1.2-3.3) Adjuvant Chemotherapy 0.9 (0.4-2.0) 0.9 (0.4-2.1)