Organ sparing management in rectal cancer. Are we there yet?

BACKGROUND: The "watch and wait" approach has recently been proposed as an alternative to surgery in locally-advanced rectal cancer patients that respond to neo-adjuvant chemoradiotherapy, in order to decrease its negative functional consequences upon the quality of life of these patients. Current methods show low accuracy for the identification of complete responders.

MATERIALS AND METHODS: A review of the literature was conducted for articles published up to March 31th, 2019. Relevant studies were identified using bibliographic searches of Pubmed database. The keywords that were used in various combinations were: "neoadjuvant chemoradiotherapy", "non-operative management", "complete pathological response", "rectal cancer", "biomarkers", "staging".

RESULTS: Magnetic resonance imaging can identify complete responders with a high accuracy using new protocols like diffusion weighted imaging. Positron emission tomography with 18-fluoro-deoxy-glucose shows a sensitivity of 90.9% and specificity of 80.3% for the prediction of complete pathologic response using the change in standardized uptake value. A panel of 15 metabolites was identified and shows potential to discriminate patient resistance and sensitivity to neo-adjuvant therapy (Area Under the Curve 0.80). Furthermore, pre-treatment peripheral blood neutrophil to lymphocyte ratio below 2 and platelet to lymphocyte ratio below 133.4 are significantly correlated with good tumor response (OR 2.49). Analysis of the pattern of carcinoembryonic antigen (CEA) clearance after neoadjuvant treatment conclude that an exponential decrease of the CEA levels is associated with significant tumor down staging and complete pathologic response.

CONCLUSION: New methods of assessing the response to neo-adjuvant therapy in locally-advanced rectal cancer have emerged, showing promising results. Further studies need to assess the best combination between imaging and these biomarkers in order to increase the accuracy and standardize the criteria for non-operative management.

KEY WORDS: Biomarkers, Complete pathologic response, Non-Operative management, Rectal cancer, Staging.