P300 - Long-term Outcomes of Intentional Watch-and-Wait and Organ Preservation Surgery Following Total Neoadjuvant Therapy in MRI-Defined Low-Risk Rectal Cancer: PKUCH-R01 Trial

Purpose/Background: Total neoadjuvant therapy (TNT) has demonstrated high rates of clinical complete response (cCR) in patients with magnetic resonance imaging (MRI)-defined low-risk rectal cancer. However, the long-term oncological outcomes of intentional watch-and-wait (W&W) or organ preservation (OP) surgery in good responders remain uncertain. Initial 3-year results from the PKUCH-R01 trial indicated favorable organ preservation rates (OPR) and survival. This study aims to report the updated 5-year long-term outcomes of the trial (NCT02860234).

Methods/Interventions: This prospective, single-arm, phase 2 trial enrolled patients with low-risk rectal cancer (cT2/T3a/T3b, MRI-staged) who underwent chemoradiation followed by four cycles of consolidation CAPEOX. Treatment response was reassessed, and patients with cCR or near-cCR were offered W&W or organ-preserving surgery, while total mesorectal excision (TME) was recommended for non-cCR cases. The primary endpoint was the 5-year OPR. Secondary endpoints: 5-year organ preservation-adapted disease-free survival (OPDFS -event comprising unsalvageable regrowth, recurrence, metastasis, or death), 5-year cancer-specific survival (CSS) and overall survival (OS). Besides, TME-free DFS was calculated, which was defined as the time from treatment start to any event that precluded organ preservation, including the need for radical TME (due to incomplete response, local regrowth, or non-salvageable recurrence), development of distant metastases, or death from any cause.

Results/Outcomes: After a median follow-up of 71.1 months, 38 patients (31 cCR, 7 near-cCR) were managed with W&W and the local regrowth rate was 21.1% (8/38). The estimated 5-year local regrowth rates were 16.1% (95% CI: 2.9%-29.3%) in cCR patients and 42.9% (95% CI: 5.5%-80.3%) in near-cCR patients. Thirty-one patients maintained sustained cCR during surveillance and 7 patients eventually underwent local excision. Distant metastasis occurred in 10.9% (5/48) of cCR/near-cCR patients and 27.7% (5/18) of non-cCR patients. The estimated 5-year TME-free survival rate was 56.3% (95% CI: 43.9 %-68.7%). The estimated 5-year TME-free DFS was 51.6% (95% CI: 39.2%-64.0%). Among the 38 patients who underwent organ preservation, 33 patients remained disease free, three patients died of other diseases and only two patients died of rectal cancer. The 5-year OP-DFS, CSS, and OS rates were 84.4% (95% CI: 75.4%-93.4%), 92.1% (95% CI: 85.3%-98.9%), and 90.6% (95% CI: 83.4%-97.8%), respectively.

Conclusion/Discussion: More than half of patients with MRI-defined low-risk rectal cancer following total neoadjuvant chemoradiotherapy plus consolidation CAPEOX achieved sustained organ preservation and remained disease-free. The excellent oncological outcomes support the use of this response-adapted treatment strategy as an attractive option for this patient subgroup.

Figure 1. (A) Table: Patient, tumor, and treatment characteristics (B) Overall consort flow diagram to show initial response, tailored treatment and organ preservation status.
LE, local excision; W&W, watch and wait; TME, total mesorectal excision; Salvage, salvage surgery after regrowth.
Figure 2. (A) Local regrowth rate; (B) TME free survival; (C) TME free disease free survival; (D) Organ preservation adapted DFS; (E) Cancer specific survival; (F) Overall survival.
DFS, disease free survival; TME, total mesorectal excision.