Intentional Watch and Wait or Organ Preservation Surgery Following Neoadjuvant Chemoradiotherapy Plus Consolidation CAPEOX for MRI-defined Low-risk Rectal Cancer: Findings From a Prospective Phase 2 Trial (PKUCH-R01 Trial, NCT02860234).

OBJECTIVE: To assess the efficacy and safety of intentional watch and wait (W&W) and organ preservation surgery following neoadjuvant chemoradiotherapy plus consolidation CAPEOX in magnetic resonance imaging (MRI)-defined low-risk rectal cancer. BACKGROUND: Clinical T2/early T3 rectal cancers can achieve high yield pathological complete response (ypCR) rates after chemoradiotherapy; thus, an intentional W&W or organ preservation strategy for good clinical responders in these subgroups can be further tested. METHODS: This prospective, single-arm, phase 2 trial enrolled patients with low-risk MRI prestaged rectal cancers, who concurrently received chemoradiation, followed by four 3-weekly cycles of CAPEOX regimen. Following reassessment, clinical complete response (cCR) or near-cCR patients underwent W&W/organ preservation surgery; the primary endpoint was a 3-year organ preservation rate. RESULTS: Of the 64 participants, 58 completed treatment, with 6.4% and 33.9% grade 3 to 4 toxicities in the radiotherapy and consolidation CAPEOX phases, respectively, during a median 39.5-month follow-up. Initial cCR, and non-cCR occurred in 33, 13, and 18 patients, respectively. Of the 31 cCR and 7 near-cCR cases managed by W&W, local regrowth occurred in 7; of these, 6 received salvage surgery. The estimated 2-year local regrowth rates were 12.9% [95% confidence interval (CI): 1.1%-24.7%] in cCR and 42.9% (95% CI: 6.2%-79.6%) in near-cCR cases, respectively. Eight patients received local excision, including 2 with regrowth salvage. Lung metastases occurred in 3 patients and multiple metastasis occurred in 1 patient; no local recurrence occurred. The estimated 3-year organ preservation rate was 67.2% (95% CI: 55.6%-78.8%). The estimated 3-year cancer-specific survival, non-regrowth disease-free survival, and stoma-free survival were 96.6% (95% CI: 92.1%-100%), 92.2% (95% CI: 85.5%-98.9%), and 82.7% (95% CI: 73.5%-91.9%), respectively. CONCLUSIONS: Chemoradiotherapy plus consolidation CAPEOX for MRI-defined low-risk rectal cancer can lead to high rates of organ preservation through intentional W&W or local excision. The oncologic safety of this strategy should be further tested.