The <scp>ACCEPTance</scp> of automation: refining circulating tumor cells enumeration for improved metastatic colorectal cancer prognosis

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with metastatic CRC (mCRC) posing significant challenges due to tumor heterogeneity and resistance to therapy. Circulating tumor cells (CTC) and circulating hybrid cells (CHC) detected via liquid biopsies have emerged as promising biomarkers for monitoring disease progression. This study aimed to evaluate the prognostic utility of automated CTC enumeration using the ACCEPT software compared to a manual method and assess the potential clinical relevance of CHC in mCRC. A retrospective analysis of CellSearch^® images from 67 mCRC patients was conducted, correlating CTC and CHC counts with progression-free survival and overall survival (OS). Automated enumeration demonstrated improved accuracy and reduced variability, confirming the prognostic significance of CTC counts for OS. However, CHC enumeration showed no significant association with clinical outcomes, suggesting sporadic detection rather than consistent prognostic value. These findings underscore the reliability of automated CTC enumeration in mCRC prognosis while highlighting the need for further research into the biological and clinical roles of CHC.