Total neoadjuvant therapy (TNT) has emerged as the standard approach for locally advanced rectal cancer (LARC), aiming to improve tumor downstaging and organ preservation. Post-TNT evaluation is crucial to identify patients eligible for a non-operative “watch and wait” strategy. This study aimed to analyze the clinical, endoscopic, and radiologic response assessment of patients with LARC who underwent TNT.

This retrospective observational study included patients who received TNT between July 2023 and June 2025 at the Gastroenterology Department of Theageneio Anticancer Hospital. Demographic, clinical, endoscopic, and imaging data were collected. Endoscopic response was categorized as complete, near complete or incomplete based on mucosal appearance (flat white scar, telangiectasia, mucosal nodularity, persistent erythema or residual ulceration). MRI response was assessed in parallel, and management outcomes (surgical vs. non-surgical) were recorded. Follow-up included endoscopic and imaging surveillance every 3-6 months. Statistically comparisons were performed using Fisher’s exact, Student’s t-, or Mann–Whitney U tests, as appropriate. 

Twenty patients were included, mean age of 68.65±8.05 years, and 11 (55 %) were male. Presenting symptoms were rectal bleeding (55%), pseudo-diarrhea (15%), perianal pain (10%), constipation (10%), anemia (10%) and tenesmus (5%). Baseline MRI staging: stage IIIB in 60%, stage IIA in 15%, and stage IIIC in 25%. After TNT, complete endoscopic response was observed in 5/20 patients (25%), characterized by a flat white scar (4/5) or telangiectasia (1/5). Near complete response was noted in 1/20(5%) with mild erythema and small mucosal nodules, while 14/20 (70%) showed no endoscopic response. MRI assessment demonstrated complete response in complete endoscopic responders, yielding a 100% concordance rate between MRI and endoscopy, these five patients were managed non-operatively under a watch-and-wait protocol, with a median follow-up of 21 months (range 10–27). Rectal bleeding was significantly more frequent in the conservative group (5/5,100%, p=0.038) than in the surgical group (6/15, 40 %). All other variables did not differ between groups. During follow-up, one patient developed local recurrence and underwent surgical resection. Fourteen patients (75%) proceeded to surgery, with one specimen showing no residual dysplasia. whereas one patient refused surgery for personal reasons. At last follow-up, all patients were alive.

Endoscopy is a valuable tool for assessing treatment response in patients with LARC undergoing TNT. Integrating systematic endoscopic evaluation into TNT response protocols may improve patient selection for organ preservation and reduce unnecessary surgery, as a substantial proportion of patients (25% in our cohort) achieve complete clinical response and can safely avoid operative management through structured endoscopic and radiologic surveillance. Familiarity of endoscopists with post-TNT findings is essential for accurate evaluation, multidisciplinary decision-making, and implementation of “watch and wait” strategies.