EP164 - Interim Report of PKUCH-R08 Study: Organ Preservation First Strategy And Intentional Watch and Wait for MRI Identified Low-risk Rectal Cancer

Purpose/Background: Clinical T2/ T3 MRI defined low-risk rectal cancers could achieve high yield-pathological complete response (ypCR) rates after neoadjuvant intensity modulated radiotherapy (IMRT) with concurrent capecitabine followed by consolidation chemotherapy. The objective of this study is to test the safety and efficacy of an organ preservation first strategy and intentional watch and wait in patients with MRI defined low-risk rectal cancers after neoadjuvant IMRT with concurrent capecitabine followed by consolidation chemotherapy.

Methods/Interventions: This is an ongoing, prospective, open-label, single-arm, multicenter, phase II trial. Patients who are MRI-staged cT2-3b rectal adenocarcinoma with the distance from the distal margin to the ARJ ≤4cm, tumor long diameter ≤4cm, MRF (-), EMVI (-) and without mucinous components will be assessed and enrolled in this study. And enrolled patients will receive 22f/25f-IMRT with concurrent capecitabine followed by consolidation chemotherapy of four cycles 21-day CAPEOX regimen. The assessments will occur in 8 and 16 weeks (3 weeks of window period) after the end of IMRT. After the 16-week reassessment, patients at initial restaging clinical complete response (cCR), near-cCR or ≤ymrT2N0 (including patients with regrowth) will be recommended for non-operative management (NOM), which included an intentional watch-and-wait (WW) strategy and local excison (LE). The primary endpoint is organ preservation rate (OPR). The secondary endpoints are incidence of adverse events, cCR and near-cCR rates, non-regrowth disease-free survival (NR-DFS), and 3-year stoma-free survival (SFS).

Results/Outcomes: Between January 17, 2024, and October 11, 2025, a total of 75 patients were enrolled in the current study, with 63 patients completing the treatment. Among the 63 patients, 53 have completed the 16-week reassessment. Among the 53 patients, 34 (64.2%) achieved cCR, 8 (15.1%) achieved near-cCR, and 7 (13.2%) achieved non-cCR with residual disease ≤ymrT2N0 and 4 (7.6%) achieved non-cCR with more than >ymrT2N0 stage. Of the 42 cCR and near-cCR patients, 41 patients were monitored through a WW strategy. One patient opted for receiving total mesorectal excision (TME) but achieved a pCR. Among seven patients with less than ymrT2N0, five have received LE resulting in ypT0, ypT3, ypTis, ypTis and ypT1, respectively, and the other two are scheduled to undergo LE. All those four patients with more than ymrT2N0 received TME resulting in pathological outcomes of ypTisN0, ypT3N1a, ypT3N0, and an undetermined result, respectively. The observed OPR was 90.6% (48 out of 53). Among those 48 cases managed by NOM, lung metastases occurred in 4 (8.3%), liver metastases occurred in 2 (4.2%) (including the one with concurrent liver and lung metastases), local regrowth occurred in 2 (one received salvage LE and the other refused to receive TME). So far, no deaths have occurred. Among the 63 patients who completed treatment, there were 7.9% and 12.6% grade 3 to 4 toxicities in the radiotherapy and consolidation CAPEOX phases, respectively.

Conclusion/Discussion: Organ-preservation first strategy after IMRT followed by consolidation CAPEOX for MRI- defined low-risk rectal cancer may lead to very high OPR, with acceptable tolerance toxicity in terms of short-term outcomes. The long-term oncologic outcomes of this strategy should be further tested.