Clinical Study Aims to Evaluate Screening Paradigm in High-Mortality Cancers

Cleveland Clinic has begun enrolling patients in a prospective, national clinical study designed to evaluate the use of a multi-cancer early detection test, which has demonstrated the ability to detect more than 50 cancers through a single blood draw. When a cancer signal is detected, it’s also able to localize the origin of the cancer signal with high accuracy.

The PATHFINDER Study marks the first time the test, developed by GRAIL, Inc., will be evaluated in clinical practice. Participants include asymptomatic patients who have an average or elevated risk for developing cancer, but no known or suspected malignancy.

Eric A. Klein, MD, Chair of Glickman Urological & Kidney Institute and principal investigator of the Cleveland Clinic arm of the study, is hopeful that this test could serve as a new screening tool for cancers that typically present at more advanced stages, are difficult to treat, and lack a broad-based screening paradigm.

Currently, early-detection screening tools exist only for five types of cancer — prostate, cervical, breast, lung and colon. Dr. Klein comments, “There are no equivalent screening resources for many other high-mortality cancers, which account for about 60% of cancer-related deaths in the United States.”

Precursor study demonstrates the test’s clinical utility

Findings from GRAIL’s Circulating Cell-free Genome Atlas (CCGA) study, a precursor study to PATHFINDER, demonstrate a high sensitivity rate from the blood-based test. The test’s sensitivity was 67.3% for stages I-III of the 12 common and deadly cancers including: anus, bladder, colon/rectum, esophageal, head and neck, liver/bile duct, lung, lymphoma, ovarian, pancreatic, stomach and plasma cell neoplasm.

Further, the test has a very low false-positive rate (0.7%) meaning that less than 1% of individuals without cancer would be wrongly identified as having cancer. In the 96% of cases when the test was able to predict where the cancer signal originated, its accuracy was 93%.

Simply put, the CCGA study was designed to assess how robust the test is in detecting known cancers, while PATHFINDER is intended to evaluate the care pathways from a cancer “signal detected” test to arriving at a diagnostic resolution.

Understanding the implications of the test results

The study intends to enroll approximately 6,200 participants across multiple different sites and follow them for 12 months. All age 50 or older, the study is enrolling eligible participants who meet criteria for the two following cohorts: those with no documented risk or history of cancer and those with elevated risk for cancer due to smoking history, previous history of invasive cancer, or genetic risk.

“Altogether, we expect the prevalence of cancer in our study population is going to be around 1.41%. If we are correct, then an overwhelming majority of participants are going to have a negative result,” says Dr. Klein. “But there are implications for both positive and negative test results.”

Positive tests will likely indicate the organ system in which the cancer signal has arisen. This information is intended to inform a diagnostic work-up and help physicians develop a subsequent care plan for patients, working hand-in-hand with their primary care provider. As part of the study, investigators will examine physician behavior after results are obtained, such as which tests are ordered and other steps taken to ultimately confirm or deny a cancer diagnosis.

There are short- and long-term implications for negative tests too, stresses Dr. Klein. A negative test may indicate no or a significantly low likelihood of malignancy, but it does not warrant abandonment of routine cancer prevention or screening. “It’s critically important that patients continue to work with their primary care physician to get routine screenings for cancers as recommended, like a colonoscopy for colon cancer, chest CT in patients who are high risk of lung cancer, PSA for prostate cancer, mammography for breast cancer, and Pap test for cervical cancer,” says Dr. Klein.

With enrollment at Cleveland Clinic now open, Dr. Klein is hopeful that they will have primary data next year. He is even more hopeful about what’s ahead.

“Even if this test detects early-stage cancer in a fraction of participants, particularly the notoriously silent and high-mortality cancers like pancreatic and ovarian, it’s really the first step in establishing a new broad-based screening paradigm for lethal cancers,” he says. “And we think that could have a big impact on cancer-related mortality.”