Predicting pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review

Aim Approximately 20% of patients treated with neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer achieve a pathological complete response (p CR ) while the remainder derive the benefit of improved local control and downstaging and a small proportion show a minimal response. The ability to predict which patients will benefit would allow for improved patient stratification directing therapy to those who are likely to achieve a good response, thereby avoiding ineffective treatment in those unlikely to benefit. Method A systematic review of the English language literature was conducted to identify pathological factors, imaging modalities and molecular factors that predict p CR following chemoradiotherapy. PubMed, MEDLINE and Cochrane Database searches were conducted with the following keywords and Me SH search terms: ‘rectal neoplasm’, ‘response’, ‘neoadjuvant’, ‘preoperative chemoradiation’, ‘tumor response’. After review of title and abstracts, 85 articles addressing the prediction of p CR were selected. Results Clear methods to predict p CR before chemoradiotherapy have not been defined. Clinical and radiological features of the primary cancer have limited ability to predict response. Molecular profiling holds the greatest potential to predict p CR but adoption of this technology will require greater concordance between cohorts for the biomarkers currently under investigation. Conclusion At present no robust markers of the prediction of p CR have been identified and the topic remains an area for future research. This review critically evaluates existing literature providing an overview of the methods currently available to predict p CR to nCRT for locally advanced rectal cancer. The review also provides a comprehensive comparison of the accuracy of each modality.