Stool-based methylated syndecan-2 testing has a high positive predictive value in an average/increased-risk...

Area of Science:

• Oncology
• Gastroenterology
• Molecular Diagnostics

Background:

• Colorectal cancer (CRC) screening is crucial for early detection and improved patient outcomes.
• Non-invasive screening methods are highly desirable for increasing population adherence.
• Stool DNA testing using methylated syndecan-2 (mSDC2) has emerged as a potential non-invasive CRC screening tool.

Purpose of the Study:

• To evaluate the positive predictive value (PPV) of the mSDC2 stool DNA test in a real-world clinical setting.
• To identify risk factors associated with the detection of advanced colorectal neoplasia (ACN) in patients with a positive mSDC2 test.

Main Methods:

• Retrospective study of patients with positive mSDC2 tests across 18 hospitals (November 2016 - July 2021).
• Patients were categorized by risk (average vs. increased) and prior colonoscopy history (previous negative vs. none).
• Multivariate logistic regression analyzed risk factors for ACN detection.

Main Results:

• The overall PPV for ACN, CRC, and any colorectal neoplasia was 28.5%, 12.8%, and 44.6%, respectively.
• PPV for ACN was significantly higher in patients with no prior colonoscopy (30.1%) compared to those with a previous negative colonoscopy (18.5%).
• Increased risk populations showed a higher PPV for ACN (41.1%) versus average-risk populations (21.6%). Old age, increased risk, and smoking were independent risk factors for ACN, while previous negative colonoscopy was protective.

Conclusions:

• The mSDC2 stool DNA test demonstrates a high PPV for ACN and CRC, positioning it as a viable alternative CRC screening strategy.
• Patients with a positive mSDC2 test should undergo prompt colonoscopy, irrespective of prior colonoscopy results.
• The test's effectiveness is supported by its performance across different risk groups and patient histories.