Neoadjuvant chemotherapy followed by transanal endoscopic surgery (TES) and selective chemoradiation or total mesorectal excision (TME) for early-stage rectal cancer: The Ottawa Hospital experience.

3627 Background: Organ-sparing therapy for early-stage rectal cancer may avoid permanent ostomy or functional disturbances commonly known as low anterior resection syndrome (LARS). TES is increasingly used for treatment of selected T1N0 or T2N0 rectal cancer. The CCTG CO.28 (NEO) phase II trial evaluated neoadjuvant chemotherapy then TES surgery for early-stage rectal cancer (Kennecke et al, JCO 2023). On the CO.28 trial, patients (pts) with post-chemotherapy ypT3N0 tumours were to have neoadjuvant chemoradiation (CRT) then TME. Pts with ypT2 or poor risk ypT1 tumours were to have TME. However, several pts insisted on organ sparing alternatives such as adjuvant CRT or active surveillance. Our approach evolved from CO.28 by incorporating more selective adjuvant CRT instead of routinely resorting to TME. Methods: This retrospective study conducted at the Ottawa Hospital evaluated the outcomes of pts with early rectal cancer treated with the NEO approach and selective adjuvant CRT. The primary outcome was 3-yr TME free survival. Secondary outcomes included safety, 3-yr disease-free survival (DFS), 3-yr permanent colostomy free survival, 5-yr overall survival (OS), pathological complete response rate (pCR), proportion of pts requiring CRT and proportion of pts with LARS at 2 yrs. Results: N = 50 pts received a NEO approach and selective adjuvant chemoradiation. N = 19 were part of the previously reported CO.28 trial and N = 31 were a consecutive cohort treated off protocol. Median age was 63 (42-83) yrs, 58% were male. Rectal location was low/mid/upper in 34%/56%/10%. Baseline T stage was T2 (76%) and T3 (10%). Neoadjuvant CAPOX (64%) or FOLFOX (36%) was completed by 88% of pts and Gr 3 AEs occurred in 31%. At TES, pCR was achieved in 32% of pts. CRT was received by 33% of pts. Median follow-up was 30.2 (2.6-86.4) months. LARS was present at 2 yr in 15%. 3-yr TME-free survival was 82% (95% C.I. 69 to 94%). 3-yr permanent colostomy-free survival was 88% (95% C.I. 78 to 99%). 3-yr DFS after all local therapy was 98% (95% C.I. 93 to 99%). One pt developed both local plus distant recurrence. 5-yr OS was 95% (95% C.I. 85 to 99%). One pt who was disease free on surveillance died of an unrelated COPD exacerbation. Conclusions: The NEO approach of neoadjuvant chemotherapy then TES combined with selective adjuvant CRT demonstrated promising organ-preservation outcomes in early-stage rectal cancer, achieving high TME-free survival. This strategy offers a meaningful alternative to routine TME, potentially reducing the risk of permanent ostomy and LARS.