Prospective Cohort Study on Multicancer Early Detection Through Blood-Based Tests: The PATHFINDER Investigation

 

Prospective Cohort Study on Multicancer Early Detection Through Blood-Based Tests: The PATHFINDER Investigation

Introduction:

Multicancer early detection (MCED) blood tests have shown great potential in identifying cancer signals from circulating cell-free DNA (cfDNA). The PATHFINDER study, a prospective cohort investigation, aimed to assess the viability of MCED testing as a method for cancer screening.

Methods:

Conducted in oncology and primary care outpatient clinics across seven prominent US health networks, this prospective cohort study involved adults aged 50 or older with no apparent cancer symptoms. Participants willingly consented to MCED testing, which involved blood collection, cfDNA analysis, and the subsequent communication of results to their healthcare providers. If a methylation signature indicative of cancer was detected, the predicted origin(s) of the cancer signal guided further diagnostic assessments. The primary endpoint was the time taken and the extent of diagnostic testing needed to confirm the presence or absence of cancer. This trial was registered at ClinicalTrials.gov (NCT04241796) and has been completed.

Results:

Between December 12, 2019, and December 4, 2020, a total of 6,662 participants were recruited for the study. Among the 6,621 participants with analyzable results, 4,204 (63.5%) were women, 2,417 (36.5%) were men, and 6,071 (91.7%) were of White ethnicity. A cancer signal was detected in 92 (1.4%) of the participants with analyzable results. Out of these, 35 (38%) were subsequently diagnosed with cancer (true positives), while 57 (62%) received no cancer diagnosis (false positives). Excluding two participants whose diagnostic assessments began before MCED test results were reported, the median time required for diagnostic resolution was 79 days (IQR 37–219). In true-positive participants, this median time was 57 days (IQR 33–143), whereas it was 162 days (IQR 44–248) for those with false-positive results. The majority of participants underwent both laboratory tests (26 [79%] of 33 true-positive results and 50 [88%] of 57 false-positive results) and imaging (30 [91%] of 33 true-positive results and 53 [93%] of 57 false-positive results). Fewer procedures were performed in participants with false-positive results (17 [30%] of 57) compared to those with true-positive results (27 [82%] of 33), and surgical interventions were rare (one with a false-positive result and three with a true-positive result).

Conclusion:

This study demonstrates the feasibility of MCED screening for cancer and emphasizes the need for further research to assess the clinical utility of this promising approach.