A new era of multi-cancer early detection blood assays
The PATHFINDER study evaluated multi-cancer early detection (MCED) screening using a blood test and the clinical care pathways following a “cancer signal detected” MCED test result in 6,662 individuals aged 50 years or older. A cancer signal was detected in 1.4% of the participants and a subsequent test confirmed a cancer in 38% of these participants. Furthermore, a high accuracy of the predicted cancer origin enabled for targeted diagnostic evaluations.
New multi-cancer early detection (MCED) tests in development can detect a common cancer signal from over 50 different types of cancer and predict where the signal has come from in the body. The signal arises from small sequences of circulating tumour DNA (ctDNA) in the blood, which have some different methylation patterns from non-tumour DNA. The PATHFINDER study is a prospective cohort study to return the results of MCED tests to participants. The study aimed to understand the diagnostic evaluations precipitated by receipt of a ‘signal detected’ MCED test result, to evaluate MCED test performance characteristics and understand the levels of participant anxiety and distress associated with MCED testing.
Study design
Participants were enrolled from December 2019 to December 2020 in the ambulatory care practices at seven US health care systems and were followed for one year from the date of MCED testing. Participants were aged ≥50 years with or without additional cancer risk factors. Patients within the additional risk cohort had a lifetime smoking history of at least 100 cigarettes, a hereditary cancer predisposition or a history of cancer with no treatment for at least three years. Blood samples were collected followed by a cell-free DNA analysis. MCED test results returned within two weeks. If no cancer signal was detected, the patient was counselled to continue recommended screening. If cancer signal was detected, the diagnostic evaluation was at the discretion of the treating physician. Cancer status was confirmed at one year for all participants. The primary outcome was the extent of diagnostic testing required for resolution after cancer signal detected by MCED. Those with cancer signal and confirmed cancer are true positive, without confirmed cancer are false positive. Key secondary outcomes included test performance and safety.
Results
Of the 6,621 people who participated in the study, most were up to date with standard screening prior to MCED testing. In the PATHFINDER study, an MCED test detected a cancer signal in 1.4% of people aged ≥50 years who were not known to have cancer. After diagnostic work-up, cancer was confirmed in 38% of those with a positive test. Of 6,290 people who were cancer free, 99.1% received a negative test result. Among those with a positive test result, the time to achieve diagnostic resolution (i.e. to find cancer or decide there was no evidence of malignancy requiring further investigation) was a median of 79 days and diagnostic resolution was achieved within three months for 73%. Of note, the median time to diagnostic resolution was longer for false positives than for true positives. Most diagnostic evaluations for participants with MCED signal detected involved imaging (92%), few required surgical invasive procedures (4%). There were no serious, study-related adverse events reported as a result of MCED testing. In addition, there were also no serious, study-related averse events due to diagnostic work-up prompted by receipt of a “signal detected” MCED test result.
A cancer signal was detected in 92 patients. Of them, 35 patients (38%) were diagnosed with cancer (solid tumours, N= 18; haematological cancer, N= 17). Among the 35 patients, 24 were included in the high-risk cohort and 11 in the non-high risk cohort. There were 7 recurrent cancers, 14 early-stage cancers and 26 cancer types for which there is no standard screening. The cancer signal origin prediction had a 97% accuracy. This is important since the predicted origin helped physicians to direct diagnostic workup. Within one year from MCED testing, 121 patients had a cancer diagnosis.
Conclusion
MCED screening was safely implemented for adults with and without additional cancer risk. In total, 1.4% of participants had a cancer signal detected. Furthermore, 0.5% of participants were diagnosed with cancer due to MCED signal detection. Median time to diagnostic resolution was 79 days. The high accuracy of predicted origin enabled targeted diagnostic evaluations. Most diagnostic evaluations involved imaging, few required invasive procedures. As such, this study showed that it is feasible to detect cancers early using blood tests.
Reference
Schrag D, et al. A prospective study of a multi-cancer early detection blood test. Presented at ESMO 2022; Abstract 903O.
