Naomi R. Zhang¹, Michael K. Edwards², Lucas M. Tanaka³, Daniel T. Roberts⁴, Hana J. Lee⁵, Haruto S. Patel⁶
ABSTRACT:
Peritoneal metastasis is a common and often fatal complication of colorectal cancer (CRC), significantly affecting prognosis and treatment strategies. Early detection and monitoring of peritoneal spread remain challenging, as conventional imaging techniques may fail to identify microscopic peritoneal metastasis until later stages. This review explores the emerging role of circulating biomarkers in the detection, diagnosis, and monitoring of peritoneal spread in colorectal cancer. We focus on both established and novel biomarkers that are detectable in blood, ascitic fluid, and other circulating body fluids, discussing their potential diagnostic applications, clinical relevance, and challenges in clinical translation. The review highlights biomarkers such as carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and newer molecular markers like miRNAs, exosomal proteins, and circulating tumor DNA (ctDNA), which have shown promise in detecting minimal residual disease or early peritoneal involvement. We examine the underlying mechanisms through which these biomarkers are involved in peritoneal dissemination, including epithelial-mesenchymal transition (EMT), tumor microenvironment interactions, and the role of the immune system in modulating metastatic progression. Furthermore, we discuss the integration of circulating biomarker data with advanced diagnostic technologies, such as liquid biopsy and next-generation sequencing (NGS), which offer high sensitivity and specificity for detecting peritoneal metastasis. The review also explores the potential of combining circulating biomarkers with imaging modalities, such as positron emission tomography (PET) and magnetic resonance imaging (MRI), to improve diagnostic accuracy and patient outcomes. Emerging technologies, including artificial intelligence and machine learning algorithms for biomarker analysis, are also addressed as tools for enhancing early detection and risk stratification. Finally, the review evaluates the clinical utility of circulating biomarkers in monitoring treatment response, detecting recurrence, and predicting overall survival in patients with colorectal cancer and peritoneal metastasis. In conclusion, circulating biomarkers hold significant promise as non-invasive, real-time tools for diagnosing and managing peritoneal spread in colorectal cancer. However, further research and validation in large-scale clinical trials are needed to establish their role in routine clinical practice and to refine their integration into personalized treatment strategies.