Assessing neoadjuvant therapy recommendations in 19 national and international guidelines for rectal cancer.

Background:  Treatment guidelines belong to the most authoritative sources of evidence-based medicine and are widely implemented by health-care providers. Rectal cancer with an annual incidence of over 730,000 new cases and nearly 340,000 deaths worldwide, remains a significant therapeutic challenge. The total mesorectal excision (TME) leads to a dramatic improvement of local control. The addition of neoadjuvant treatment has been proposed to offer further advancement. However, this addition results in significant functional impairment and a decline in the quality of life.

Methods: This review critically assesses whether the recommendation for neoadjuvant treatment in current international guidelines is substantiated. A comprehensive search was conducted in July 2022 in PubMed resulting in 988 papers published in English between 2012 and 2022. After exclusions and proofs 19 documents remained for further analysis.

Results: Of the 19 guidelines considered in this review, 11 do not recommend upfront surgery, and 12 do not address the issue of functional impairment following multimodal treatment. The recommendation for neoadjuvant therapy relies on outdated references, lacking differentiated strategies based on current utilisation of MRI staging; numerous guidelines recommend neoadjuvant treatment also to subgroups of patients, who may not need this therapy. Also statements regarding conflicts of interest are often not presented.

Conclusions: An immediate and imperative step is warranted to align the recommendations with the latest available evidence, thereby affording rectal cancer patients a commensurate standard of care. A meticulous assessment of the guideline formulation process has the potential to avert heterogeneity in the future.