Clinical Outcome for Rectal Cancer Treated with Preoperative Chemoradiotherapy (CRT) Based on the Pathological Tumor Regression Grade (TRG)

Purpose: Preoperative Chemoradiotherapy (CRT) followed by surgery for rectal cancer shows promising results because it can improve the local control, which translates into a better long-term overall survival and disease-free survival, especially more notable for rectal tumors which showed marked pathological response to preoperative CRT. The aim of this study is to retrospectively review and analyze the prognostic significance of the American Joint Committee on Cancer (AJCC) Tumor Regression Grade (TRG) response for rectal cancer patients receiving preoperative CRT. Methods: The case record of 58 biopsy-proven adenocarcinoma of the rectum who received preoperative CRT from the 2006 to 2020 was retrospectively reviewed. All patients received whole pelvis radiotherapy for 50 Gy in 25 fractions concurrently with oral Tegafur-uracil and calcium folinate or oral capecitabine followed by surgery later. This study’s end point was to evaluate the TRG score of the rectal tumor, its correlation with patient’s local control and survival. The Kaplan-Meier method estimation of survivorship, multiple regressions, the log-rank test and Cox proportional hazard model were used for statistical analysis. Results: A total of 58 pathologically proven adenocarcinoma of rectum treated with preoperative CRT from April, 2006 to October, 2020 were retrospectively reviewed. The male-to-female ratio was 3.5 to 1; the median age was 61 years old (26 to 90 years). All patients were treated with preoperative Image-Guided Intensity Modulated Radiotherapy (IG-IMRT). Surgery was performed after a median interval of 8.6 weeks (5.3 to 16 weeks). The Local-Regional Recurrence (LRR) rate was 8.6% (n=5/63), while Distant Metastasis (DM) occurred in 22.4% (n=13/58). Tumor down staging after preoperative CRT was seen in 35 patients (60.3%). Multiple regression analysis showed that age (p=0.007), clinical T stage (p=0.029), clinical N stage (p=0.025) and time interval between CRT and surgery (p=0.015) significantly affected the TRG score, the TRG score after preoperative CRT in turn have a significant effect on the local control (p=0.005). TRG 0 showed the best survival benefit with the estimated 5-year and 10-year OS for TRG 0, 1, 2, 3 were 100%, 84.6 %, 58.7%, 0% and 88.2%, 84.6%, 0%, 0% (log-rank test, p=0.0002) respectively, while the estimated 5-year and 10-year DFS for TRG 0, 1, 2, 3 were 93.9%, 72.0%, 40.4%, 0% and 82.9%, 54.0%, 0%, 0% (log-rank test, p=0.004) respectively in our study. The 5-year and 10-year overall survival for ypStage 0 and ypStage were 100%, 88.2%, 93.9%, 82.9% and 91.7%, 38.2%, 73.7%, 29.5% respectively. Cox regression analysis showed that resection margin status and TRG significantly affected the overall survival. Conclusion: Our study showed that the TRG response and the associated tumor down staging after preoperative CRT is an important significant prognostic factor affecting patient outcome, specifically the tumor local control and patient survival. The TRG system should be implemented for prognostication of rectal cancer treated with preoperative CRT.