Circulating Tumor DNA Detects Minimal Residual Disease in Patients with Locally Advanced Rectal Cancer After Total Neoadjuvant Therapy

<b>Background/Objectives</b>: Nonoperative management (NOM) of patients with locally advanced rectal cancer (LARC) who achieve a complete clinical response (cCR) to total neoadjuvant therapy (TNT) has been shown to be oncologically safe and is an attractive treatment option for patients. However, identifying responders to TNT that may benefit from nonoperative management is clinically challenging. Circulating tumor DNA (ctDNA) testing has shown promise in detecting minimal residual disease but has not yet been studied extensively within this clinical context. <b>Methods</b>: This is a single-institution retrospective case series study of LARC patients treated with TNT from 2019 to 2023 who underwent ctDNA testing as an adjunct to standard clinical response assessments. <b>Results</b>: A total of 28 patients had ctDNA testing as part of their response assessments after TNT. In total, 9 patients had positive ctDNA, and 19 patients had negative ctDNA during surveillance. Baseline characteristics of these two groups were not different. In this study, 6/9 (67%) patients who had positive ctDNA required surgery for residual rectal cancer, whereas only 4/19 (21%) patients who had negative ctDNA required surgery (<i>p</i> = 0.035). <b>Conclusions</b>: ctDNA testing has the potential to detect MRD in LARC patients treated with TNT.