The Prognostic Importance of ctDNA in Rectal Cancer: A Critical Reappraisal

SIMPLE SUMMARY: An individualized treatment approach is necessary to improve survival and quality of life in rectal cancer. Tools to stratify patients are missing, but ctDNA seems to be a good candidate. Current results are sparse, conflicting and characterized by lack of a uniform approach. As the interpretation of results is dependent on the quality of reporting, we aimed to address this issue in our paper. Our results indicate an association between ctDNA status and outcome. In six out of nine papers, bias was low. However, a conclusion is dubious because of the heterogeneity among the studies and lack of standardized methods. Studies addressing these issues are warranted. ABSTRACT: The treatment of locally advanced rectal cancer (LARC) has evolved during the last decades, but recurrence remains a problem. Circulating tumor DNA (ctDNA) may result in an individualized treatment approach with improved survival and quality of life, but diverging results impede further development. In this systematic review, we addressed the quality of reporting and its impact on the interpretation of ctDNA results. We performed a systematic literature search using subject headings and search terms related to ctDNA and rectal cancer. The Quality of Prognostic Studies (QUIPS) tool was used to assess bias. Nine studies, with substantial heterogeneity, were included in the analysis. Three out of nine articles had moderate or high risk of bias. No association was found between treatment response and ctDNA status at baseline. There was a negative association between ctDNA positivity at baseline, before and after surgery and survival. The ctDNA status may be of importance to the long-term prognosis, but the area of research is new and is short of dedicated studies. There is an obvious need for standardization in ctDNA research, and the issue should be addressed in future research.