Local Regrowth and the Risk of Distant Metastases Among Patients Undergoing Watch-and-Wait for Rectal Cancer: What Is the Best Control Group? Muticenter Retrospective Study

A proportion of patients that achieve a clinical complete response may develop local regrowth. While salvage appears to provide appropriate local control, the risk of distant metastases is less known.Compare the risk of distant metastases between patients that achieve a complete clinical response (watch-and-wait strategy) and subsequent local regrowth to patients managed by surgery after chemoradiation.Retrospective multicenter cohort study.This study used data of patients from 3 institutions that were treated between 1993 and 2019.Patients with initial clinical complete response (after neoadjuvant therapy) followed by local regrowth and patients with near-complete pathological response (≤10%) after straightforward surgery after chemoradiation.Univariate/multivariate analysis was performed to identify risk factors for distant metastases. Kaplan-Meier curves were created (log-rank test) to compare survival outcomes. Analysis were performed using time-zero as last day of radiation therapy (1) or as date of salvage resection (2) in the local regrowth group.Twenty-one of 79 patients with local regrowth developed distant metastases while only 10 out of 74 after straightforward surgery (p = 0.04). Local regrowth and final pathology (ypT3-4) were the only independent risk factors associated with distant metastases. When using date of salvage resection as time-zero, distant-metastases-free survival rates was significantly inferior for patients with local regrowth (70 vs. 86%; p = 0.01).Small number of patients, many neoadjuvant therapies, selection bias.Patients undergoing watch-and-wait who develop local regrowth are at higher risk for development of distant metastases compared to patients with near-complete pathological response managed by surgery upfront after chemoradiation.