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

Purpose: 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.

Methods: 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.

Results: 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).

Conclusion: 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.