Neoadjuvant Radiotherapy Versus No Radiotherapy for Stage IV Rectal Cancer: a Systematic Review and Meta-analysis

The aim of this study is to review the contemporary evidence comparing neoadjuvant radiotherapy (NRT) versus no radiotherapy (no RT) in patients with stage IV rectal cancer.

Literature was searched for studies using the following databases: Pubmed, EMBASE, Science Direct, Scopus, ASCOpubs, the Cochrane Library, and Google Scholar. Studies reporting outcomes for stage IV rectal cancer patients who underwent NRT or no RT were selected.

A total of eight studies were included in this review (one RCT, five retrospective cohorts, two population-based studies). The only RCT in this review reported no significant difference in 2- and 5-year local recurrence (NRT versus no RT) 10.1% versus 23.8%, and 15.9% versus 26.9%, respectively. However, multivariate analysis showed the effect of treatment might not have differed between subgroups according to stage. Pooled analysis from five retrospective studies showed significantly improved local recurrence-free survival (LRFS) with NRT (risk ratio [RR] 1.15; 95% CI 1.01-1.31, p = 0.03), which was maintained in the subgroup who underwent metastasectomy. (RR 1.18; 95% CI 1.01-1.37, p = 0.04). Pooled 5-year overall survival (OS) showed a statistically significant benefit with NRT (RR 1.47; 95% CI 1.14-1.89, p = 0.003), which was not seen in the subgroup who underwent metastasectomy (RR 1.31; 95% CI 0.94-1.82, p = 0.11).

The current available evidence shows an LRFS benefit with NRT over no RT in patients with stage IV rectal cancer. The review also suggests a possible OS benefit with NRT, although this finding should be interpreted with caution.