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

Abstract

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.

Neoadjuvant radiotherapy improves overall survival for T3/4N+M0 rectal cancer patients: a population-based study of 20300 patients

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Delivery of Personalized Care for Locally Advanced Rectal Cancer: Incorporating Pathological, Molecular Genetic, and Immunological Biomarkers Into the Multimodal Paradigm

“…However, there are many patients whose outcomes do not match those typical for their tumor stage and accurate prognostic information for individual patients can be difficult to estimate owing to the heterogeneous nature of the disease. Many new combinations of chemotherapy with radiotherapy, including total neoadjuvant therapy (TNT) with targeted therapies that aim to diminish toxicity and increase survival, are being evaluated in clinical trials (10,11). Despite these advances, local recurrence and distant metastasis remain an issue, with one-third of LARC patients dying within 5 years of initial treatment (10).…”

Minimally invasive rectal surgery: Laparoscopy, robotics, and transanal approaches

“…The management of rectal cancer is constantly evolving. Some of the recent changes in rectal cancer management are directed toward the sequencing of multidisciplinary treatment including the use of total neoadjuvant therapy which incorporates neoadjuvant radiation and neoadjuvant chemotherapy before surgery 1,2 . Moreover, the concept of overtreatment in rectal cancer has lead to investigations on the selective use of radiation and as well as the concept of nonoperative management of rectal cancer 3‐5 .…”