Background: Total neoadjuvant therapy (TNT) for rectal cancer (RC) can achieve clinical complete response (cCR) and organ preservation in as many as 45% of patients, with watch-and-wait (WW) management. For tumors that persist or regrow after TNT, standard management is total mesorectal excision (TME), which can result in poor bowel function or permanent colostomy. In certain cases, only residual adenoma or mucosal based carcinoma may remain after TNT. Local excision (LE) is a minimally invasive surgical alternative that preserves the rectum. Here we evaluate case selection, safety, and efficacy of LE for small tumors that persist or regrow after TNT. Methods: Our retrospective review identified 72 RC patients from August 2010 – July 2023 who underwent LE for tumors that either remained after TNT or achieved cCR and later regrew. Median follow up from end of TNT was 3.2 years. LE was selectively offered if the tumor was suspected to arise from an adenoma or a small cancer confined to mucosa, based on clinical impression and biopsy. Collected data included tumor characteristics and pathology, surgical complications, length of stay (LOS), local and distant tumor recurrence, and organ preservation. Results: Pretreatment MRI staging was 5% T1, 23% T2, 68% T3, and 4% T4. Median distance from anal verge was 4.8 cm. 90-day complications after LE included dehiscence (6%), rectal pain (5%), transient urinary retention (4%), bleeding (4%), and minor incontinence (4%). One patient developed pelvic sepsis requiring drainage of perirectal abscess and fecal diversion. Median LOS was 1 day (range 0-4). Pathologic review demonstrated invasive cancer in 27 LE specimens, while 45 had either benign pathology or carcinoma in situ (table 1). R1 pathology was present in 8 of 27 (30%) invasive cancer specimens. 6 of 27 (22%) patients with invasive cancer (3 ypT1, 3 ypT2) subsequently underwent TME. 3 of 27 patients (11%) developed distant metastases. Of the 45 patients with benign LE pathology, 3 (7%) later required TME for subsequent cancer regrowth (range 4-22 months after LE). 4 of 45 patients (8%) developed distant metastases. Overall organ preservation rate following LE was 87.5%, with median follow-up of 2.4 years after surgery. For all 9 LE patients who ultimately underwent TME, there were no pelvic recurrences and one distant recurrence. Conclusions: Small, mucosal based tumors that contain minimal or no invasive cancer are common findings after TNT. For appropriately selected patients, LE is a safe and effective initial option, given high observed rates of local control and organ preservation, with low surgical morbidity. If more advanced disease is encountered on final pathology, TME should be considered. These data support the use of LE as an important adjunct to WW management.