Watch-and-Wait Strategy Against Surgical Resection for Rectal Cancer Patients with Complete Clinical Response after Neoadjuvant Chemoradiotherapy

Abstract

Background: The watch-and-wait strategy offers a non-invasive therapeutic alternative for rectal cancer patients who achieved clinical complete response (cCR) after chemoradiotherapy. However, concerns about the safety of this treatment strategy remain. Methods: Stage II/III rectal adenocarcinoma patients who received neoadjuvant chemoradiotherapy and achieved cCR from Sept 1, 2010 to Jan 30, 2018 at three centers in China were included. cCR patients who adopted the watch-and-wait strategy were compared to cCR patients who had standard surgical resection. The primary end point was disease-specific survival (DSS). All end points were calculated and compared with log-rank test in a non-matched cohort and a 1:3 ratio propensity-score paired match cohort. Findings: 471 cCR patients were included, of which 354 were in the watch-and-wait group and 354 in the surgical group. Compared to the surgical group, patients managed by watch-and-wait had earlier T-stage but more distally located tumors, of whom 22 patients had local regrowth, and 17 of them were salvaged by surgery. Ultimately, sphincter preservation was achieved in 108 (92*3%) patients in the watch-and-wait group, and in 283 (79*9%) patients in the surgical group (p=0*002). The 3-year distant metastasis-free survival (DMFS) were 89% versus 87%, 3-year DSS were 99% versus 96% and the 3-year overall survival were 99% versus 96% for the watch-and-wait and the surgical group, respectively. After matching, difference in T-stage was not significant, and survival analyses also showed no significant difference between the two groups. We did observed a lower 3-year DMFS in patients with local regrowth compared to those with sustain cCR (75% versus 93%, p=0*044), however, this was comparable to the 3-year DMFS of the non-pathological complete responders of the surgical group (p =0*730). Interpretation: Rectal cancer patients achieving cCR and treated with the watch-and-wait strategy had similar survival outcomes but superior sphincter preservation rate as compared to those who underwent radical surgery and a trend of higher distant metastasis rate observed in local regrowth patients should not be considered as the main concern for treatment decision. Funding Statement: The National Natural Science Foundation of China (81672987). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All the procedures were approved by the ethical committee at each center, which also waived the necessity of patients’ informed consent due to the retrospective nature of this study.