Clinical Evaluation of Cancer Signal Origin Prediction and Diagnostic Resolution following Multicancer Early...

Area of Science:

• Oncology
• Diagnostic Medicine
• Biotechnology

Background:

• Blood-based multi-cancer early detection (MCED) tests are emerging tools for cancer screening.
• Evaluating cancer signal detected (CSD) results and predicting cancer signal origin (CSO) are critical steps in the diagnostic pathway.

Purpose of the Study:

• To assess the diagnostic utility of CSO prediction-guided evaluations for MCED test results.
• To determine if participants with risk factors and negative initial evaluations were diagnosed with cancer during follow-up.
• To evaluate the role of whole-body imaging (WBI) and compare diagnostic journeys for true- and false-positive MCED results.

Main Methods:

• Analysis of diagnostic journeys for 39 participants with CSD on initial and refined MCED tests in the PATHFINDER study.
• Evaluation of CSO prediction-directed diagnostic workups and subsequent diagnostic resolution.
• Assessment of WBI utility and comparison of diagnostic procedures (imaging, surgical, non-surgical) between true- and false-positive results.

Main Results:

• 82% of participants achieved diagnostic resolution after initial evaluation, with 78% specifically using CSO prediction-directed workups.
• 18% required additional evaluation for persistent suspicion, all achieving resolution (some with cancer, some without).
• WBI contributed to resolution in 49% of CSD cases; 90% of cases had imaging, with true-positives more likely to undergo procedures than false-positives (81% vs 38.9%).

Conclusions:

• CSO prediction-directed evaluations effectively facilitated diagnostic resolution for the majority of participants with MCED-detected signals.
• Persistent clinical suspicion in initially negative evaluations necessitated further testing, ultimately leading to resolution.
• The study highlights the importance of guided diagnostic pathways and the varied utility of imaging and procedures in confirming MCED findings.