e15639 Background: Total Mesorectal Excision (with or without chemoradiation) has been the established standard of care for the treatment of localized rectal cancer. Neoadjuvant Chemoradiation (nCRT) followed by Local Excision (LE) has been proven as a safe alternative approach for selected patients. This study aims to review the current evidence of this strategy, guided by the disease response from the nCRT. Methods: database research was performed through PubMed, Embase, and Cochrane Central for prospective studies evaluating the use of nCRT followed by LE in localized rectal cancer patients. Our primary outcomes were Local Recurrence Rates (LRR) correlated to patients’ pathological response status. We pooled the proportions of binary outcomes and their 95% confidence intervals. I² analysis was used to assess heterogeneity. We performed statistical analyses using R software version 4.3.1 with a random-effects model. Our analysis was prospectively registered with the number CRD42024499095 (PROSPERO). Results: A pool of 760 citations was initially screened, and 5 prospective trials assessing nCRT following LE in at least one of the arms were selected with a pooled analysis of 438 patients (including CRT-LE single arm, or randomization with CRT followed by total mesorectal excision and short course radiation alone). Neoadjuvant treatment was performed with a radiation dose ranging between 45 - 54Gy and concomitant fluoropyrimidine (5-fluorouracil or Capecitabine) isolated or in combination with Oxaliplatin. The extracted data was subgrouped into favorable responders (FR) (complete or near-complete pathological response) or unfavorable responders (UR). Looking specifically at the nCRT+LE arm, 284 patients were identified, from which 168 were classified as FR (59.1%). The pooled LRR was 0.02 (95% CI 0.00-0.06; I² = 27%) for this group. A total of 116 patients were classified as UR, with a polled LRR of 0.09 (95% CI 0.05-0.16; I² = 0%). Conclusions: Our analysis demonstrate that nCRT + LE is a safe strategy, with data from 5 prospective trials demonstrating very low local recurrence rate, especially in the group of patients who achieved a good response to the neoadjuvant approach. Treatment intensification protocols aiming to achieve a higher response rate can potentially reduce the local recurrence in those patients.