Performance and safety of a multi-cancer early detection test: the PATHFINDER 2 study

Key Points:

• PATHFINDER 2 was a large prospective study enrolling 35,878 participants aged 50 or older without clinical suspicion of cancer to evaluate the performance and safety of a multi-cancer early detection (MCED) blood test, with 35,350 participants analyzed.
• The MCED test showed high specificity (99.64%) and a positive predictive value (PPV) of 60.3%, detecting cancer in 0.54% of participants, with a 12-month episode sensitivity of 39.3% overall and higher sensitivity in aggressive cancers and those causing most US cancer deaths.
• Safety analysis revealed a low rate of invasive diagnostic procedures (0.6% of tested participants), mostly non-surgical, with few and non-serious adverse events reported; anxiety increased temporarily only in participants with true-positive results.
• The MCED test detected a broad range of cancer types, including many lacking current USPSTF screening recommendations, and detected more cancers when added to existing screening methods, potentially enabling earlier-stage diagnosis and curative treatment.
• Limitations include the single-arm design, one-time testing, and use of an earlier test version; randomized trials and longer follow-up are needed to confirm clinical utility, but PATHFINDER 2 supports the MCED test’s robust performance and favorable safety profile in a screening population.