Validation of Multi-Target Stool DNA Methylation Test for Colorectal Cancer Detection: A Preliminary Analysis

Colorectal cancer (CRC) develops gradually from precancerous adenomas and is highly curable when detected early. In Malaysia, however, most cases are diagnosed at advanced stages, leading to poorer outcomes despite the availability of screening programmes such as the immunological Faecal Occult Blood Test (iFOBT). Limited screening uptake and poor adherence contribute to delayed diagnosis. Therefore, effective non-invasive and patient-friendly screening tools are essential. Background/Objectives: This study aims to validate the diagnostic performance of the multi-target stool DNA (mt-sDNA) test. Methods: This cross-sectional validation study was conducted at the Endoscopic Center, Hospital Canselor Tuanku Muhriz (HCTM), from January 2024 to September 2025. Adults aged 18-75 years undergoing elective or emergency colonoscopy were included. Results: Among 246 patients, most were male (56.5%), Malay (65.2%), and aged 55-75 years (91.3%). CRC prevalence was 8.5%. A significant association was observed between age group and colonoscopy findings (p = 0.005), with older individuals more likely to have CRC or adenomatous lesions. Most CRC (90.4%) and advanced adenoma (84.6%) cases occurred in symptomatic patients; however, this difference did not demonstrate a significant association with colonoscopy outcomes (p = 0.069). Per rectal bleeding, constitutional symptoms, altered bowel habit, abdominal pain and constipation were significantly associated with CRC and adenomatous lesions. The mt-sDNA test showed a sensitivity of 63.2%, specificity of 85.0%, positive predictive value of 36.4%, and negative predictive value of 94.4%. Conclusions: Preliminary findings indicate that mt-sDNA demonstrates good specificity and high negative predictive value, but moderate sensitivity and low positive predictive value.