SUMMARY: The American Cancer Society estimates that in 2023, 1,958,310 new cancer cases and 609,820 cancer deaths are projected to occur in the United States. Although cancer mortality rates continue to decline with advances in treatment, improving early detection can reduce disease and treatment-related morbidity, improve treatment outcomes, quality of life and reduce financial burden both for the patient as well as the society as a whole. Currently the USPSTF (Unites States Preventive Services Task Force) and ACS (American Cancer Society) recommend screening for breast, cervical, colorectal, and lung cancers. Neither the ACS nor USPSTF have specific recommendations for prostate cancer screening. These cancers collectively account for only 42% of annual cancer incidence in people aged 50-79 years. It has been estimated that detection of cancer at an earlier stage could reduce cancer-related deaths by 15% or more within 5 years. Some of the available screening tests reduce cancer-specific mortality, but are associated with high false-positive rates, overdiagnosis, and overtreatment.
Galleri is a Multi-Cancer Early Detection (MCED) test developed for the early detection of multiple asymptomatic cancers that lack recommended screening tests, using a blood sample. DNA (cell free DNA) is shed into the blood stream both by tumor cells as well as healthy cells. The Galleri test uses Next Generation Sequencing (NGS) and machine-learning algorithms to isolate cell-free DNA and analyze more than 100,000 DNA regions and over a million specific DNA sites, to screen for a signal shared by cancers. The test looks for cell-free DNA and identifies whether it comes from healthy or cancer cells. DNA from cancer cells has specific methylation patterns that identify it as a cancer signal. Methylation patterns also contain information about the tissue type or organ associated with the cancer signal. So, once a cancer signal is detected, the Galleri test predicts the Cancer Signal Origin, or the tissue or organ where the cancer signal originated, to help guide diagnostic evaluation. The Galleri test is recommended for use in adults with an elevated risk for cancer, such as those aged 50 or older, and should be used in addition to routine cancer screening tests. Galleri is not recommended in individuals who are pregnant, 21 years old or younger, or undergoing active cancer treatment.
A validation study (Circulating Cell-free Genome Atlas study-CCGA) was conducted to evaluate the accuracy of the Galleri test. This study included 2,823 people with a known diagnosis of cancer and 1,254 healthy people. The overall Sensitivity for cancer signal detection was 51.5% and the Specificity was 99.5%. The sensitivity of the test increased with advanced cancer stages. Cancer signals were detected across over 50 cancer types and the overall accuracy of predicting Cancer Signal Origin in those who tested true positive was 88.7% (Ann Oncol. 2021;32:1167-1177).
PATHFINDER was a pilot, prospective cohort study conducted to investigate the feasibility of MCED testing for cancer screening. This study included 6,621 participants from oncology and primary care outpatient clinics at seven U.S. health networks who underwent MCED blood testing. Participants were 50 years or older, with no signs or symptoms of cancer, and majority were women (63.5%) and White (91.7%). Approximately 56% of participants had additional risk factors such as smoking, germline cancer predisposition, or personal history of treated cancer. The Primary outcome was time to diagnosis, and extent of diagnostic testing required to confirm the presence or absence of cancer.
MCED testing detected a cancer signal in 1.4% of the total patient sample of whom 38% had cancer confirmed (true positives), while 62% had no cancer (false positives). In patients in whom no cancer signal was detected, 95.5% were true negatives, 1.3% was false negatives, and 3.2% did not have cancer-status assessment at the end of the study. The tests accuracy in predicting the primary cancer location (Cancer Signal Origin) among the true positives was high at 97%. The median time to achieving a diagnostic resolution was 79 days, 57 days in true-positive patients and 162 days in false-positive ones. Fewer procedures were done in participants with false-positive results compared to true-positive results (30% versus 82% respectively) and few participants had surgery (one with a false-positive result and three with a true-positive result).
Among participants whose testing was true-positive and who had a confirmed new cancer diagnosis, nearly half (48%) were detected at an early stage (Stage I-II) when the potential for curative treatment is increased. Further, 74% of the MCED-detected cancers were cancer types that do not currently have USPSTF screening recommendations. These included cancers of the bile duct, pancreas, small intestine, and spindle cell neoplasm, which are all associated with high mortality rates and may be amenable to surgical resection at early stages.
In the 12 months study period, 121 cancers were diagnosed, of whom 29% had a cancer signal detected by MCED, while 31% were detected thru screening and 40% were detected clinically. The overall Positive Predictive Value of MCED was 38%, Negative Predictive Value was 98.6%, and specificity was 99.1%. The cancer yield rate was 0.53% (number needed to screen to find one MCED-detected cancer was 189).
The researchers concluded that this study demonstrates the feasibility of screening for multiple cancers using a blood test and lays the foundation for large, controlled trials necessary to establish clinical utility and cost-effectiveness. Multi Cancer Early Detection test was also able to accurately predict tumor origin, and the diagnosis of cancer was established in less than 2 months in the true-positive patients.
Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study. Schrag D, Beer TM, McDonnell CH, et al. The Lancet 2023;402:1251-1260.
