Systematic review of outcomes after total neoadjuvant therapy for locally advanced rectal cancer

BACKGROUND: Advances in surgical technique and the development of combined-modality therapy have led to significantly improved local control in rectal cancer. Distant failure rates however, remain high, ranging between 20 and 30 per cent. Additional systemic chemotherapy in the preoperative period has been proposed as a means of eradicating subclinical micrometastases and improving long-term survival. The purpose of this systematic review was to evaluate the current evidence regarding induction chemotherapy in combination with standard neoadjuvant chemoradiotherapy, in terms of oncological outcomes, in patients with rectal cancer. METHODS: A systematic review of the literature was performed to evaluate oncological outcomes and survival in patients with rectal cancer who underwent induction chemotherapy and neoadjuvant chemoradiotherapy, followed by surgical resection. Four major databases (PubMed, Embase, Scopus and Cochrane) were searched. The review included all original articles published in English reporting long-term outcomes, specifically survival data, and was limited to prospective studies only. RESULTS: A total of 686 studies were identified. After applying inclusion and exclusion criteria, ten studies involving 648 patients were included. Median follow-up was 53·7 (range 26-80) months. Five-year overall and disease-free survival rates were 74·4 and 65·4 per cent respectively. Weighted mean local recurrence and distant failure rates were 3·5 (range 0-7) and 20·6 (range 5-31) per cent respectively. CONCLUSION: Total neoadjuvant therapy should be considered in patients with high-risk locally advanced rectal cancer owing to improved chemotherapy compliance and disease control. Further prospective studies are required to determine whether this approach translates into improved disease-related survival or increases the proportion of patients suitable for non-operative management.