Counting Advanced Precancerous Lesions as True Positives When Determining Colorectal Cancer Screening Test...

Area of Science:

• Oncology
• Biomarker Discovery
• Health Services Research

Background:

• The Centers for Medicare & Medicaid Services (CMS) established specific performance thresholds for blood-based biomarkers for colorectal cancer (CRC) screening.
• Current CMS guidelines define sensitivity at 74% or higher and specificity at 90% or higher, excluding advanced precancerous lesions from positive results.

Purpose of the Study:

• To evaluate the impact of including advanced precancerous lesions as true positives in CRC screening test performance.
• To project CRC incidence and mortality outcomes under different screening test scenarios using a validated model.

Main Methods:

• A validated modeling approach was used to simulate CRC outcomes.
• The study contrasted the effects of defining advanced precancerous lesions as true positives versus false positives.
• Performance metrics including sensitivity and specificity were analyzed.

Main Results:

• A test meeting CMS thresholds (74% sensitivity, 90% specificity) projected a 30% decrease in CRC incidence and a 48% decrease in CRC mortality for individuals aged 45.
• Incorporating detection of advanced precancerous lesions (30% sensitivity) further reduced CRC incidence by 45% and mortality by 58%.
• However, this improved test had 88% specificity, falling below the CMS threshold.

Conclusions:

• CMS should reconsider its specificity threshold for CRC screening biomarkers to potentially include tests that detect precancerous lesions.
• Future coverage decisions for cancer screening biomarkers should account for the detection of precursor lesions and overall projected health outcomes.