Importance of Tumor Regression Grade in ypStage III Rectal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy

Abstract

Complete and partial tumor regressions are associated with improved long-term outcome in patients with rectal cancer after neoadjuvant chemoradiotherapy (NCRT). ypStage III rectal cancer consists of lymph node positive patients with heterogeneous prognosis. Introducing tumor regression grade (TRG) into heterogeneous ypStage III rectal cancer may provide clue on selecting out patients who might acquire maximal benefit from intensified adjuvant treatment. This study was performed to evaluate the prognostic impact of the tumor regression grade in ypStage III rectal cancer patients treated with NCRT. In this retrospective study, 287 patients with locally advanced rectal cancer received NCRT at our institution from 2003 to 2015. ypStage III patients were classified into two subgroups based on the combination of ypStage and TRG: ypStage III patients with good TRG (TRG 3-4) and ypStage III patients with poor TRG (TRG 1-2). Median follow-up time was 51.3 months. 5-year overall survival (OS) and 5-year distant metastasis-free survival (DMFS) were 86.0% and 78.5%, respectively. When ypStage III patients were divided into ypStage III & TRG 3-4 subgroup and ypStage III & TRG 1-2 subgroup, ypStage III & TRG 1-2 patients had worse 5-year OS (95.8% vs. 62.0%, p = 0.023) and 5-year DMFS (78.8% vs. 56.1%, p = 0.073) compared to the ypStage III & TRG 3-4 patients. And there were no differences between the ypStage II subgroup and the ypStage III & TRG 3-4 subgroup in terms of the 5-year OS (86.9% vs. 95.8%, p=0.405) and 5-year DMFS (79.3% vs. 78.8%, p=0.683). Multivariate analyses showed that grouping patients into 3 modified subgroups – ypStage 0-I, ypStage II/ypStage III & TRG 3-4, and ypStage III & TRG 1-2 – clearly divides patients and this grouping itself becomes the most important prognostic factor for predicting OS (p<0.001) and DMFS (p<0.001). Degree of tumor regression after NCRT significantly divided heterogeneous ypStage III rectal cancer patients into two groups: ypStage III patients with good TRG (TRG 3-4) and ypStage III patients with poor TRG (TRG 1-2). Therefore, TRG may be used to discern a high-risk group in ypStage III patients who might benefit from more intensified adjuvant treatment.