Genetic testing key to targeting prostate cancer

Urologists are central to the more appropriate use of genetic screening.

Isla P. Garraway, MD, PhD
Isla P. Garraway, MD, PhD

Genetic testing is one of the most useful and least used diagnostic tools in many practices.

“Cancer is a heritable disease; prostate cancer is the most heritable of all cancers,” said Isla P. Garraway, MD, PhD, professor and director of research in urology at the David Geffen School of Medicine at the University of California, Los Angeles. “Having a single first-degree relative with prostate cancer increases your risk 2-3 times. Having a relative with prostate cancer diagnosed earlier than 65 or having three or more relatives with prostate cancer increases risk 6-11 times over baseline.”

Dr. Garraway opened the International Prostate Forum on Sunday. A key focus of the half-day forum was the growing utility of germline and somatic testing as the array of therapeutic agents targeting specific genetic variants such as BRAF1 and 2 continues to grow.

Germline variants (or mutations) are changes to an individual’s base DNA inherited from their parents. Germline DNA is present in every cell that contains a nucleus and can be sampled from cheek swabs and many other locations.

Somatic mutations are acquired DNA variations that occur after conception. Samples are typically taken from tumor biopsies.

Both can affect prostate cancer risk.

National Comprehensive Cancer Network guidelines recommend genetic testing for any man with metastatic diseases, a family history of prostate cancer or the presence of genes such as BRCA1/BRCA2 associated with increased cancer risk, Dr. Garraway noted.

“The only way to definitively identify individuals with heritable and potentially actionable genetic variants is through germline DNA testing,” Dr. Garraway said.  “Urologists are the first line in the diagnosis of prostate cancer. We should be thinking about genetic screening, and then we need to make the appropriate referrals to medical oncology, genetic testing and clinical trials.”

Urologists themselves are a key barrier to the more appropriate use of genetic screening.

“Genetic testing may not be part of the daily life and lexicon of many urologists,” said Raoul S. Concepcion, MD, chief science officer at U.S. Oncology Partners. “Genetic testing can help us better identify patients who do not need to be treated, as well as the most appropriate treatments for individual patients.”

A 2019 consensus conference on implementing germline testing identified three key barriers.

Providers worry about medical/legal liability for unaddressed mutations. If they don’t test, they are not liable for mutations.

Providers also worry about reimbursement for these high-cost tests and the challenges of entering genetic data into the electronic health record.

U.S. Oncology has developed a model to streamline testing and treatment recommendations based on the Litholink model, Dr. Concepcion said. A beta version was trialed in 2022 and is being expanded to additional practices in 2023.

Somatic testing can also help uncover targetable mutations in tumors

“I use it with all my patients who have metastatic disease,” said Peter Carroll, MD, MPH, professor of urology at the University of California, San Francisco. “Somatic testing does not replace conventional risk assessment; it is a very useful complement.”

Somatic testing is equally helpful in active surveillance, particularly for intermediate- and high-risk patients.

“Somatic risk helps you verify the risk of progression associated with other factors,” Dr. Carroll said. “Somatic tests add value.”

Most somatic testing requires tumor biopsies. Liquid biopsies, sequencing circulating tumor cells (CTCs) and cell-free DNA (cfDNA) are the next steps.

“Liquid biopsies could have a huge impact on screening,” Dr. Carroll said. “cfDNA in particular is a frontier to explore.”

More Content