Prognostic value of tumour regression grade in locally advanced rectal cancer: a systematic review and meta-analysis

The current standard of care for locally advanced rectal cancer involves neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision. There is a spectrum of response to neoadjuvant therapy; however, the prognostic value of tumour regression grade (TRG) in predicting disease-free survival (DFS) or overall survival (OS) is inconsistent in the literature.

This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was undertaken using Ovid MEDLINE, Embase and Google Scholar. Inclusion criteria were Stage II and III locally advanced rectal cancer treated with long-course CRT followed by radical surgery. The aim of the meta-analysis was to assess the prognostic implication of each TRG for rectal cancer following neoadjuvant CRT. Long-term prognosis was assessed. The main outcome measures were DFS and OS. A random effects model was performed to pool the hazard ratio (HR) from all included studies.

There were 4875 patients from 17 studies, with 775 (15.9%) attaining a pathological complete response (pCR) and 719 (29.9%) with no response. A significant association with OS was identified from a pooled-estimated HR for pCR (HR = 0.47, P = 0.002) and nonresponding tumours (HR = 2.97; P < 0.001). Previously known tumour characteristics, such as ypN, lymphovascular invasion and perineural invasion, were also significantly associated with DFS and OS, with estimated pooled HRs of 2.2, 1.4 and 2.3, respectively.

In conclusion, the degree of TRG was of prognostic value in predicting long-term outcomes. The current challenge is the development of a high-validity tests to predict pCR.