The U.S. Department of Veterans Affairs (VA) has two weapons of unprecedented power that are already having a mighty effect on cancer research and treatment: its sheer magnitude and its infrastructure. With 1,323 VA care sites and 173 medical centers across the U.S. and a massive patient population of about 9 million, the VA also has the longest-working electronic health record in the country, going back more than 25 years.
In a remarkable partnership, PCF and the VA have established 21 VA Prostate Cancer Centers of Excellence where, on the treatment side, Veterans have access to genetic sequencing (detailed analysis of genes) of their metastatic tumor, state-of-the art care including precision oncology therapies, and access to precision clinical trials. In addition, investigators including Michael Lewis, M.D., a pathologist at the Greater Los Angeles VA (GLA-VA) are reviewing this data to find ways to help Veterans at every step of the prostate cancer journey, from diagnosis and treatment to survivorship.
These records complement the colossal VA-MAPP database, which PCF Chief Science Officer Howard Soule, Ph.D., believes is “the largest biorepository in any field of oncology, anywhere in the world.” What’s in it? In addition to detailed clinical data, blood samples, saliva, PSA test results, biopsy samples, tissue samples from localized and metastatic prostate cancers – much of which has undergone genetic sequencing. These samples can be correlated with MRI and PSMA-PET scans, and also examined alongside records of environmental or service-related exposures that could lead to prostate cancer: Agent Orange, for instance, or exposure to water contaminants, burn pits, or atmospheric radiation. VA-MAPP is putting Veteran health data to work for Veterans facing a diagnosis of prostate cancer.
Simply put, there is nothing comparable, anywhere, in depth or breadth to this trove of data. And all of it is being used to help Veterans.
A Strong Tradition of VA Pathology Excellence
If you have been diagnosed with prostate cancer, or are living with metastatic prostate cancer, you really need to know what kind of cancer you’re dealing with – information that comes from the pathologist’s analysis of your primary or metastatic tumor.
As it turns out, the VA has a long tradition of expertise in prostate cancer pathology; in fact, the grading system for prostate cancer bears the name of a VA pathologist. More than 50 years ago, Donald Gleason, M.D., the former chief of pathology at the Minneapolis VA Medical Center, did something no one else had been able to do: he figured out a way to classify prostate cancer based on the cell patterns he saw under the microscope. His method, known as the Gleason score, is still used worldwide.
Now VA pathologist Lewis, building on this strong foundation, is working to advance prostate cancer pathology even further – toward precision diagnosis, based on molecular findings, for all Veterans. Lewis and his team perform in-depth analysis of patients’ metastatic tumors, including sequencing the genes and immune signature (the particular immune cells involved in fighting, or not fighting, cancer). The team is part of the PCF-VA David Geffen Foundation Precision Oncology Center of Excellence. “Pathology plays a key role in making cancer care more personalized,” says Lewis, “because precision treatment starts with a precision diagnosis.”
How precise? Lewis and his team aren’t just studying cancer cells from biopsy slides or surgical specimens, as Gleason did. They’re also examining evidence of metastatic cancer that can be found in the blood: analyzing circulating tumor cells, and even profiling the DNA and RNA from prostate cancer that is floating around in the bloodstream. These scientists are learning more than ever before from tiny bits of genetic information that until the last few years were not routinely studied at all. VA investigators are also applying “omics” – a deep-dive approach to biological analysis of prostate cancer, looking within the genes and studying entire collections of molecules (“omes”) in the body, such as the genome (genes), proteome (proteins), microbiome (bacteria and viruses), and others.
The state-of-the-art analysis provides the patient with the most information and the most potential options for treatment, Lewis says. In other words, it’s not your father’s prostate cancer path report. Today, the Gleason grade is just the starting point.
“The VA is at the forefront of precision pathology,” says Lewis. “Studies have shown that Veterans with prostate cancer are getting top-of-the-line care, regardless of race and ethnicity. It doesn’t matter where you reside; you can get the best care, period.”
Up until a few years ago, Lewis says, pathologists did genomic sequencing of tissue only from the primary tumor. But cancer evolves as it grows and spreads, and metastatic tissue – biopsy samples from a lymph node or lung lesion, for example – provides the most comprehensive genomic information. Every patient receives top-of-the-line genomic analysis of tumor tissue for biomarkers that could guide precision treatment. The test looks for known cancer-causing alterations in key DNA damage repair genes, including: BRCA1, BRCA2, ATM, and many others.
“Genomic testing can tell us which patients will benefit most from gene-targeted drugs – PARP inhibitors such as olaparib – and/or immunotherapy,” says Lewis. “The more options we can find for treatment, the better off our patients will be.” Plus, “our findings can help the patient’s family members, as well,” if an inherited mutation is found in a gene such as BRCA1 or BRCA2 – genes linked to breast, ovarian, colon and other cancers
The GLA-VA team also performs DNA sequencing to determine the “immune landscape profile” – to see whether a patient might benefit from checkpoint inhibitor immunotherapy. “Labs from across the VA send samples to us,” Lewis continues, “and we do our analytical work in an expeditious way. If you have metastatic cancer, you need answers quickly.”
In other research using the VA-MAPP database, Lewis and colleagues at the GLA-VA are looking for dangerous genetic changes in primary cancer. In a study published in BMC Cancer, investigators analyzed genetic signatures for chromosomal instability (linked to aggressive prostate cancer) in biopsy samples from GLA-VA patients. Their findings may lead to new ways to identify men at high risk of lethal prostate cancer – who could benefit from targeted therapy – at the time of their initial diagnosis.
Lewis is part of a multidisciplinary team at GLA-VA that includes medical oncologists, radiation oncologists, urologists, nuclear medicine experts, and research scientists. “We have thousands of patients here locally with prostate cancer,” he says. “This collaborative group, with visionary leadership from PCF and the VA, allows us to keep pushing the envelope of getting Veterans better health care, and better outcomes with more precision. We treat every patient as if he were a member of our own family.”
“We Offer This to Every Single Vet Who Wants Help”
Every Veteran who sends his slides or materials to Lewis’s team gets a full genomics and molecular sequence profile of his cancer, and these results are paired with clinical trials. “We’re now doing virtual and digital patient consent for trials, even for patients in rural areas. A patient can get access to a trial in Los Angeles” or at another PCF-VA Center of Excellence. For this, Lewis credits Dr. Mary (Molly) Klote, the VA’s Deputy Chief Research and Development Officer. “She and her team have streamlined processes and removed a lot of barriers,” to make it possible for Veterans with prostate cancer anywhere to have access to clinical trials.
Today, 16,000 Veterans are living with a diagnosis of metastatic prostate cancer. Most of these Veterans have access to precision diagnosis and treatment, says Lewis. “We are sent hundreds of referrals from all across the country,” he says. A lot of these referrals come through plain old word of mouth, from “Veterans talking to each other, in person, on Facebook, or online chat groups. If you are a Veteran with prostate cancer, reach out! We offer this to every single Vet who wants help,” Lewis continues. “When they send their samples to us in LA, they can be followed up either by care at their local VA, or Veterans can get a referral to be seen at GLA-VA,” either in person or via telemedicine. (Note: For more information, please call or email: Laura Onstad, RN at (503)-721-1060 or email at [email protected].)
