Molecular Cancer Signal Localization in MCED Testing Minimizes Radiation and Imaging Burden Compared with Whole-body...

Area of Science:

• Medical Diagnostics
• Oncology
• Radiology

Background:

• Diagnostic evaluation of multi-cancer early detection (MCED) tests requires strategies to differentiate true positives from false positives (FPs).
• Current approaches may involve extensive imaging, leading to increased radiation exposure and healthcare costs.

Purpose of the Study:

• To compare the efficiency and radiation exposure of two post-positive MCED test diagnostic strategies: a cancer signal origin (CSO)-guided approach with repeat MCED testing (CSO-Retest) versus a Whole-body imaging (WBI)-Only strategy.
• To evaluate the impact of MCED test specificity on false positive rates and imaging requirements.

Main Methods:

• A previously published model was extended to compare the CSO-Retest strategy with the WBI-Only strategy (employing whole-body computed tomography (WBCT) followed by PET/CT).
• Analyses considered two scenarios with varying test performance characteristics and specificities.
• Outcome measures included the number of imaging procedures and radiation exposure for each strategy.

Main Results:

• The CSO-Retest strategy demonstrated a 10- to 20-fold reduction in WBCT/PET/CT use compared to the WBI-Only strategy.
• A 1% decrease in WBI-Only test specificity (from 99.5% to 98.5%) resulted in a >3-fold increase in FPs and more than doubled WBI requirements.
• Estimated radiation exposure for CSO-Retest ranged from 0-26.1 mSv, while the WBI-Only strategy mandated 28 mSv for initial evaluations.

Conclusions:

• CSO-guided diagnostic strategies incorporating targeted workups and MCED retesting substantially reduce radiation exposure and imaging burden compared to WBI-only approaches.
• Even minor reductions in MCED test specificity can lead to a significant increase in unnecessary diagnostic workups and associated radiation exposure.