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Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: A Systematic Review and Metaanalysis of Oncological and Operative Outcomes

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Total neoadjuvant therapy in rectal cancer refers to the administration of chemoradiotherapy plus chemotherapy before surgery. Recent studies have shown improved pathological complete response and disease-free survival with this approach. However, survival benefits remain unproven. Our objective is to present a metaanalysis of oncological outcomes of total neoadjuvant therapy in locally advanced rectal cancer.

Patients and Methods

A comprehensive search was performed on PubMed, Medline, and Google Scholars. Studies comparing total neoadjuvant therapy with standard neoadjuvant chemoradiotherapy were included. Data extracted from the individual studies were pooled and a metaanalysis performed. The outcomes of interest are the rate of complete pathological response, nodal response, resection margin, anal preservation, anastomotic leak, local recurrence, distant recurrence, disease-free survival, and overall survival.

Results

There were 15 comparative studies with 2437 patients in the neoadjuvant chemoradiotherapy group and 2284 in the total neoadjuvant therapy group. The pooled complete pathological response was 22.3% in the total neoadjuvant therapy group, compared with 14.2% in the standard neoadjuvant chemoradiotherapy group (p < 0.001). Even though there was no difference in local recurrence rate, there was a significantly lower rate of distant recurrence (OR 0.81, p = 0.02), and better 3-year disease-free survival (70.6% vs. 65.3%, respectively, p < 0.001) and overall survival (84.9% vs. 82.3%, respectively, p = 0.006), favoring the total neoadjuvant therapy group. Due to significant heterogeneity in the study protocols, there remains uncertainty on the ideal chemotherapy/radiotherapy sequence.

Conclusions

This study provides supporting evidence on the favorable immediate and intermediate oncological outcomes with the use of total neoadjuvant therapy for locally advanced rectal cancer.

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Author notes

  1. Joseph C. Kong and Mikael Soucisse are co-first authors and have contributed equally to this study.

Authors and Affiliations

  1. Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Joseph C. Kong MBChB, FRACS, PhD, Mikael Soucisse FRCSC, Jacob McCormick FRACS, MS, Satish K. Warrier MBBS, FRACS, MS & Alexander G. Heriot FRACS, MD, MBA

  2. Division of Cancer Research, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Joseph C. Kong MBChB, FRACS, PhD, Satish K. Warrier MBBS, FRACS, MS & Alexander G. Heriot FRACS, MD, MBA

  3. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, Australia

    Joseph C. Kong MBChB, FRACS, PhD, Michael Michael FRACP, MD, Jeanne Tie MBChB, FRACP, MD, Samuel Y. Ngan MBBS, FRANZCR, Trevor Leong MD, MBBS, FRANZCR, Satish K. Warrier MBBS, FRACS, MS & Alexander G. Heriot FRACS, MD, MBA

  4. Division of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Michael Michael FRACP, MD & Jeanne Tie MBChB, FRACP, MD

  5. Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Samuel Y. Ngan MBBS, FRANZCR & Trevor Leong MD, MBBS, FRANZCR

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  1. Joseph C. Kong MBChB, FRACS, PhD
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Contributions

Joseph Kong, Mikael Soucisse and Alexander Heriot: Substantial contributions to the conception and design, acquisition of data, or analysis and interpretation of data. All authors: Drafting and revising the article. All authors: Final approval of the version to be published.

Corresponding author

Correspondence to Joseph C. Kong MBChB, FRACS, PhD.

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Kong, J.C., Soucisse, M., Michael, M. et al. Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: A Systematic Review and Metaanalysis of Oncological and Operative Outcomes. Ann Surg Oncol 28, 7476–7486 (2021). https://doi.org/10.1245/s10434-021-09837-8

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