Assessing adjuvant chemotherapy benefit in younger and older molecular residual disease–positive patients with stage II/III colorectal cancer.

216 Background: Identifying patients with colorectal cancer (CRC) who derive benefit from adjuvant chemotherapy (ACT) presents a significant challenge. This is especially true given the aging patient population, which accounts for over half of all new CRC diagnoses and represents a diverse group susceptible to chemotherapy toxicities. The survival benefit of oxaliplatin-based regimens (doublet ACT) for younger patients with stage III CRC is well-established; however, this has not been conclusively demonstrated for patients aged 70 or older, and clinical uncertainty remains. This retrospective study assessed disease-free survival (DFS) in younger and older patients with molecular residual disease post-surgery when treated or not treated with ACT. Methods: Among 6,061 patients from the GALAXY cohort, patients (N= 260) with stage II or III CRC and with ctDNA-positivity during the molecular residual disease (MRD) window (2-10 weeks post surgery) were included in the analysis. A tumor-informed, 16-plex PCR-NGS assay (Signatera Natera, Inc.) was used for ctDNA analysis. This study evaluated DFS among MRD-positive patients when stratified by age (≥70 years vs.