The Surveillance Nonoperative Watch & Wait (SNOWW) Rectal Cancer Trial.

The primary objectives of this study are to determine if the inclusion of ctDNA testing in the evaluation and management of stages 2 and 3 rectal cancers will allow clinicians to improve their selection of patients for wait and watch (WW) management and to facilitate the detection of cancer regrowth during WW surveillance.

Inclusion Criteria: 1. Provision to sign and date the consent form. 2. Stated willingness to comply with all study procedures and be available for the duration of the study. Additional Inclusion Criteria: Pre-TNT phase Adult male and female patients (\>18 years old) Clinical stage 2 or 3 rectal cancer, within or beyond the reach of digital rectal exam (DRE), who are evaluated in a multidisciplinary setting and who will receive induction or consolidation total neoadjuvant therapy (TNT) and are candidates for watch and wait management (WW) with curative intent. Post-TNT phase complete or near complete clinical response to TNT High-definition flexible endoscopy: Pale smooth scar with or without telangiectasia No ulceration, nodularity, or mucosal irregularities No stricture DRE: Smooth, flat scar No nodularity Diffusion-weighted MRI2 Fibrotic, linear scar with low signal intensity on T2-weighted images No diffusion restriction No suspicious lymph nodes Near Complete Clinical Response: Endoscopic appearance with irregular small mucosal nodules, superficial ulceration, or mild persistent erythema DRE: Smooth induration or superficial minor mucosal irregularity MRI: T2-weighted MRI with downstaging with or without residual fibrosis, small area of residual signal, and complete or partial regression of lymph nodes. Diffusion-weighted MRI with small area of residual high signal intensity Exclusion Criteria: * • Patients who are less than 18 years old * Patients who are pregnant during the study period * Patients with stage I or IV rectal cancer * Patients who receive neoadjuvant therapy other than TNT. * Patients who receive short-course neoadjuvant radiotherapy. * Patients who are actively enrolled in other clinical trials that prohibit inclusion in this study. * Patients who refuse or are unable to undergo ctDNA testing and subsequent follow ups * Patients who refuse or are unable to undergo WW management of rectal cancer. * Patients who are undergoing "WW" management of rectal cancer due to refusal of recommended surgical resection. (For example, the hypothetical patient with an incomplete clinical response to TNT who refuses surgery). * Patients who undergo WW for palliation only. * Patients with prior history of rectal cancer with or without chemoradiation treatment or surgical resection * Patients who have a different cancer, in addition to rectal cancer, in whom the study ctDNA testing would be uninterpretable.