PATHFINDER was a prospective cohort study of multicancer early detection (MCED) testing in an outpatient ambulatory population. The aim of this study is to report the patient-reported outcomes (PROs) collected as secondary and exploratory measures in the PATHFINDER study.

PATHFINDER is a prospective, multicentre, cohort study that enrolled existing healthy ambulatory outpatients at seven health networks in the USA, including hospitals, academic medical centres, and integrated health systems. Enrolled adults were aged 50 years or older without clinical suspicion of cancer, with or without additional cancer risk factors (smoking history, genetic predisposition, or previous cancer diagnosis). The primary objective was time to diagnostic resolution after an MCED cancer signal detected (CSD) result and extent of testing pursued. The objectives of the 12-month PATHFINDER study reported here were assessment of patient-reported outcomes and perceptions with MCED testing (the effect of the MCED test result disclosure, general anxiety symptoms, health-related quality of life, and satisfaction with the MCED test). PRO instruments used included an adapted Multidimensional Impact of Cancer Risk Assessment (MICRA) for distress, uncertainty, and positive experience at MCED test result disclosure; PRO Measurement Information System (PROMIS) Anxiety short-form for anxiety symptoms; and Short Form 12-Item Health Survey (SF-12v2) for health-related quality of life. Intentions towards adherence to guideline recommended screening was also assessed as an exploratory objective. This study is registered at ClinicalTrials.gov, NCT04241796, and is complete.

Between Dec 12, 2019, and Dec 4, 2020, 6662 participants were recruited and 6621 eligible participants had analysable MCED test results (n=92 CSD and n=6529 no CSD [NCSD]). The majority of participants were women (4204 [63·5%] of 6621) and White (6071 [91·7%] of 6621). For participants who completed the MICRA at results disclosure, the mean total MICRA score was 28·4 (SD 14·9) for the 50 patients with a CSD result and 8·8 (7·2) for those with an NCSD result (n=5864 completed the full questionnaire). Mean general anxiety scores increased in true-positive and false-positive groups at results disclosure. The PROMIS anxiety true-positive group baseline score of 46·2 (SD 6·5; n=35) increased to 48·4 (7·3; n=19) and the scores in the false-positive group increased from 47·3 (7·3; n=52) to 49·7 (7·7; n=30). Mean scores in both groups returned towards baseline by end of study (true positive 46·8, SD 8·0; n=28; false positive 46·9, 8·1; n=41). Mean SF-12v2 mental component summary and scale scores were within the average general population range at all timepoints. A high proportion of participants (5749 [97·1%] of 5920) responded they were “satisfied”, “very satisfied”, or “extremely satisfied” with the MCED test, with this proportion highest in those with NCSD (5698 [97·2%] of 5861), followed by those with a true-positive MCED result (23 [92·0%] of 25) and those with a false-positive result (28 [82·4%] of 34). Most participants indicated they were likely or very likely to adhere to health-care providers’ future cancer screening recommendations at end of study (5182 [95·6%] of 5418).

The negative patient-reported effects associated with a CSD result from MCED testing were small and returned to baseline within 12 months for participants with or without a cancer diagnosis. PATHFINDER results indicate potential clinical benefit of early cancer detection and minimal patient distress associated with MCED testing.

GRAIL.