A genetic test developed by researchers at Broad Clinical Labs and the U.S. Department of Veterans Affairs (VA) is now being tested in a large, nationwide clinical trial aimed at improving detection of prostate cancer. The low-cost method could potentially identify men at high risk who may benefit from earlier prostate cancer screening. The trial is called the Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS).
“If the ProGRESS and other trials are successful, primary care doctors will be able to quickly and objectively measure each patient’s prostate cancer risk. This information will empower them to take appropriate steps to prevent the all-too-common scenarios of metastatic prostate cancer and fatal prostate cancer,” senior author of the paper Tyler Seibert, MD, PhD, told Inside Precision Medicine. Seibert is an associate professor and radiation oncologist at UC San Diego.
The paper appeared January 26 in Nature Cancer, and the lead author is Jason Vassy, MD, a physician-scientist with the VA Boston Healthcare System and Mass General Brigham, associate professor of medicine at Harvard Medical School, and leader of the ProGRESS clinical trial.
“Recruitment into the trial is ongoing. There has been a lot of interest and uptake of the study. We will then follow these men to see whether they undergo prostate cancer screening in a way that minimizes harms while preserving the benefits of screening,” he told Inside Precision Medicine.
Prostate cancer is the second-leading cause of cancer deaths in U.S. men. The American Cancer Society estimates that about one in eight men will be diagnosed with prostate cancer during their lifetime. But each man’s risk of prostate cancer can vary, based on his age, race/ethnicity, and other factors. Also important is the fact that many men will survive the disease to die of something else, complicating treatment decisions.
Broad Clinical Labs (BCL) developed the DNA sequencing approach underpinning the test. And reports that a growing number of healthcare and other organizations are partnering with BCL to use this approach, called ‘the clinical blended genome-exome,’ to provide low-cost genetic testing for studies on a variety of diseases including heart disease and cancer.
The team’s polygenic score (PHS601) includes common genomic markers throughout the whole genome that can be detected with a “low-resolution” scan of the DNA. But some patients, explains Seibert, have rare pathogenic mutations (e.g., in the BRCA1 gene) that cannot be detected unless deeper sequencing is done of each amino acid in the gene of interest.
“The blended genome-exome assay is a Goldilocks approach: deep sequencing of the genes in the DNA that have the code to make proteins and low-pass (“low-resolution”) sequencing of the DNA that sits between those genes,” Seibert said.
In diagnosing prostate cancer, the aim to make cancers that would metastasize are found while they are still small and curable. But doctors need to do that without casting such a wide net that they find a bunch of harmless cancers and treat patients who don’t need it.
“The key question in predicting prostate cancer risk is to identify the people who are at highest risk of developing aggressive prostate cancers so that we can focus our screening efforts on those most likely to benefit,” said Seibert.
The researchers have further goals. “First, we want to understand if our predictions of prostate cancer risk can be more specific—i.e., can we predict specifically patients’ risk of developing aggressive cancer, not just their risk of developing any prostate cancer. Second, and probably more important, once we find an early-stage prostate cancer, we need to better distinguish/predict which of these will behave aggressively if left untreated—and which will not. We have a lot of great projects ongoing to make progress on both fronts,” Seibert said.
“The blended genome-exome is dollar for dollar one of the best value genetic tests you could get today, and we’re excited to see it power a variety of studies looking to accelerate the implementation of genomic medicine, which is core to the mission of Broad Clinical Labs,” said Niall Lennon, PhD, a study co-author and chief scientific officer and chair of BCL.
