Optimal timing for curative surgery after preoperative chemoradiotherapy in locally advanced rectal cancer.

Abstract

677 Background: This study is a multicenter retrospective analysis conducted by the Korean Radiation Oncology Group (KROG) to identify the optimal operation timing after preoperative chemoradiotherapy (CRT) in rectal cancer. Methods: The study included data of 1786 patients who were diagnosed with locally advanced rectal cancer (cT3-4N0-2M0) and received preoperative CRT followed by curative surgery from 2003 to 2014, at 8 institutions in Korea. Total radiation dose was 50.4 Gy in 28 fractions, delivered in 1.8 Gy per fraction. All patients received total mesorectal resection. Interval time between preoperative CRT and surgery ranged from 1 week to 136 weeks, and median interval time was 7 weeks. Downstaging rate was assessed by comparing clinical pre-CRT and pathological post-CRT stages and downstaging was defined as ypStage 0-I (ypT0-2N0M0). Pathologically complete response (ypCR) was defined as the complete absence of viable tumor (ypT0N0M0). Primary end point of this study was to evaluate the period of highest downstaging and ypCR rates to determine the optimal timing for surgery after CRT. Results: Analyses on downstaging and ypCR rates were done with all patients. Downstaging rates peaked between 6 and 7 weeks and declined afterwards. ypCR rates increased from 5 to 6 weeks and decreased after 9 to 10 weeks. The patients were divided into two arms according to the median interval time between preoperative CRT and surgery. Downstaging rates were similar between the two arms showing 36.9% in the early arm (≤ 7 weeks) and 37.0% in the delayed arm ( > 7 weeks). However, ypCR rates were significantly higher in the delayed arm, compared to the early arm (12.3% vs. 8.6%, p = 0.011). Complete tumor regression was superior in the delayed arm, as compared to the early arm (13.2% vs. 9.1%, p = 0.004). The delayed arm had higher sphincter preservation rates than the early arm with a marginal significance (92.4% vs. 89.9%, p = 0.078). There was no statistically significant difference regarding overall survival and disease-free survival. Conclusions: The optimal timing for surgery for advanced rectal cancer is after 7 weeks and before 10 weeks following preoperative CRT.