ctDNA to Guide Adjuvant Therapy in Localized Colorectal Cancer (CRC)

SIMPLE SUMMARY: The assessment of risk of recurrence following surgery in patients with localized colorectal cancer (CRC) is crucial to indicate systemic adjuvant therapy. The presence of circulating tumor (ct)DNA in the plasma of patients after treatment with curative intent has recently been defined as minimal residual disease (MRD). Detection of MRD is a powerful prognostic biomarker which reflects the presence of micrometastasis and can potentially guide the need of systemic treatment before becoming clinically evident. The aim of this review was to highlight and explore the current situation of MRD detection in CRC cancer and its potential impact in routine clinical practice. ABSTRACT: Currently, the standard treatment for patients with localized colorectal cancer (CRC) includes surgical resection followed by adjuvant chemotherapy based on clinicopathological features. Recurrence risk stratification in those patients is of utmost importance to guide clinicians to avoid both under- and overtreatment. Recently, the concept of minimal residual disease (MRD) has emerged as the detection of circulating tumor DNA (ctDNA) carrying tumor-specific genomic or epigenomic alterations in the bloodstream of patients after surgery. Emerging studies described how the detection of MRD is a powerful prognostic biomarker to identify patients at higher risk of recurrence and who will potentially benefit the most from a systemic adjuvant treatment. Based on that unprecedented finding, several clinical trials involving stage II and III CRC patients are ongoing evaluating the impact of ctDNA guided treatment by escalating or deescalating adjuvant chemotherapy based on ctDNA MRD detection. This review provides a critical overview of current perspectives of liquid biopsy in early-stage CRC including technical, biological, and clinical key points, as well as ongoing ctDNA-based clinical trials that ultimately aim to improve clinical outcomes of patients with CRC.