Circulating tumor cells and circulating tumor DNA have been extensively studied in metastatic colorectal cancer with regard to their diagnostic, prognostic, and predictive impact; however, data of direct comparison between these two techniques are lacking.

Circulating tumor DNA yields higher sensitivity and suitability than circulating tumor cells, thus being the main plasma biomarker employed in clinical trials and closer to reach clinical practice for metastatic colorectal cancer. However, circulating tumor cells boast the unique potential to serve as a platform for ex vivo culture and xenografting.

Randomized clinical trials are needed to establish how to integrate liquid biopsy to improve the prognosis of patients affected by metastatic colorectal cancer.