2289 - Organ Preservation-First Strategy Following Total Neoadjuvant Chemoradiotherapy for MRI-Defined Low-Risk Rectal Cancer: Early Results from a Prospective, Single-Center, Phase II Trial (PKUCH-R08)

Purpose/Objective(s): To evaluate the efficacy and safety of an organ preservation-first strategy in patients with MRI-defined low-risk rectal cancer following total neoadjuvant therapy (TNT).

Materials/Methods: Eligible patients had MRI-defined low-risk rectal cancer (T2-T3b, tumor size =4cm, distance to ARJ =4cm; histological grade 1-3; MRF-negative; EMVI-negative; no mucinous component). They received VMAT 50.6Gy/22 fractions with concurrent capecitabine, followed by 4 cycles of CAPEOX. Response was assessed by MSKCC criteria. Patients with clinical complete response (cCR) entered watch-and-wait (W&W). Those with near-cCR opted for either local excision (LE) or W&W. LE was also offered for residual or regrowth tumor =T2N0, while total mesorectal excision (TME) was indicated for =T3N0 or any N+ disease. The primary endpoint was 3-year organ preservation rate (OPR). Secondary endpoints included treatment toxicity, cCR/near-cCR rates, and 3-year organ-preservation DFS.

Results: Between Jan 2024 and Jul 2025, 67 eligible patients were enrolled (41 males, 26 females) with a median age of 63 years (range: 37–79). Baseline staging revealed 36 T2 and 31 T3a/b tumors. The median distance to ARJ was 0cm (range: 0–4.0) and median tumor size was 3.1cm (range: 1.0–4.0). All patients completed the scheduled radiotherapy, and 88.1% (59/67) completed 4 cycles of CAPEOX. Grade 3-4 toxicity rates were 4.5% in VMAT and 20.9% in consolidation CAPEOX. Following TNT, 42 (62.7%) achieved cCR and 13 (19.4%) achieved near-cCR. Eight (11.9%) had residual tumor =T2N0, and 4 (6.0%) had residual tumor =T3N0. Among the 55 patients with cCR/near-cCR, 53 adopted W&W, one received LE, and one received TME. Among 8 patients with =T2N0 disease, 6 received LE, 1 refused LE, and 1 received TME. All 4 patients with =T3N0 disease received TME. R0 resection rate was 100%. No high-grade surgical complications occurred. LE pathology showed 4 pT0, 5 pTis–2, and 1 pT3. TME pathology showed 1 pCR, 2 pTis–2N0, 3 pT3N0, and 1 pT3N1. After a median follow-up of 13.3 months (range 4.6-24.3), 5 W&W patients had local regrowth (3 =T2N0 received LE, 1 received TME, 1 refused TME), including 1 with synchronous distant metastasis; 3 additional patients had distant metastasis alone. The 1-year OPR was 86.6% (58/67).

Conclusion: Organ preservation-first strategy is safe and significantly increases OPR in MRI-defined low-risk rectal cancer following TNT. The long-term oncological outcomes need further investigation.