Originally published 3/31/2018
In the blog below, which we posted in early 2018, urologists are called upon to pay close attention to the family history of men newly diagnosed with prostate cancer (PCa). A family history of prostate or breast cancer is an obvious reason to test for gene mutations that are markers for potentially aggressive PCa. In fact, PCa genomic screening guidelines from the National Comprehensive Cancer Network (NCCN) recommend germline genetic testing with or without genetic counseling for PCa patients who have:
- A positive family history of cancer (eg, prostate, breast)
- High-risk, very-high-risk, regional or metastatic prostate cancer, regardless of family history
- Ashkenazi Jewish ancestry
- Intraductal histology
In terms of high-risk cell lines, as well as PCa predisposition, the guidelines also list specific gene variants or mutations to screen for.
According to a study of over 3000 PCa patients by Nicolosi, et al. (2019), 17.2% of the men tested had a potentially dangerous germline variant. The problem is, over a third of them (37%) did not qualify for testing according to the NCCN guidelines. Since most PCa patients are in the hands of urologists, this startling statistic underscores the call to action described below. We hope that awareness of the need for increased screening practices continues to grow, so that patients who appear to have low-risk disease but carry a hidden danger can be identified early in order to strategize best-care treatment plans.
Calling all urologists!
In 2008, a new professional organization for urologists was established. Called the Large Urology Group Practice Association, it came about in part because of the trend toward a urology business model based in economic efficiencies: large practices with a single administrative center. For example, Urology Associates of North Texas (UANT) currently has 40 urologists in their practice; or, the Michigan Institute of Urology boasts a medical staff of 55, including physician assistants and other licensed specialists. Thus, LUGPA was “established with the purpose of enhancing communication among large groups, allowing for benchmarking of operations, promoting quality clinical outcomes, developing new opportunities, and improving advocacy in the legislative and regulatory arenas.”
LUGPA’s 2017 annual meeting was held in Chicago Nov. 10-11. One of the presenters, Dr. Leonard Gomella, issued a call to all urologists to integrate genetic testing for prostate cancer into their practices.
Importance of genomic analysis
Urology is the specialty that most commonly deals with prostate cancer (PCa). With ongoing science, urologists recognize that some types of PCa have an inherited, or genetic, component. For instance, men have a 50% chance of being diagnosed with PCa if they have a first degree relative (father, brother, son) who has the disease. Also, it is now accepted knowledge that men are at greater risk for PCa if they have a female relative who has had breast cancer (BCa); in fact, a simple test can determine if a man is carrying the BRCA1 or BRCA2 gene mutations, the same ones that place a woman at high risk for BCa.
Dr. Gomella states that the field of medicine is rapidly moving toward personalized healthcare based on knowledge of each individual’s genetic make-up and risk factors. This means tailoring and targeting PCa treatment for the aggressiveness of the specific cell line. The problem for urologists dealing with PCa is that not many “have a deep knowledge of whom they should screen, or what to do with that data.”[i]
Who should be screened?
Dr. Gomella emphasizes that the problem is broader than a family history of PCa or BCa. It is essential that urologists take the time to obtain a detailed family history, which can inform screening decisions. He says there are many cases in which a single genetic mutation is associated with a particular disease or cancer, but it’s more complex when it comes to PCa. There are cancers beyond prostate, breast and ovarian cancers that should “raise a trigger about the potential for prostate cancer risk.”[ii] Families in which pancreatic cancer, gastric cancers, and the Lynch syndrome (genetic condition with a high risk for a number of cancers) have occurred may indicate a need for “panel testing” in which multiple mutations and genetic factors can be identified, as well as how they interact with other to increase PCa risk.
Dr. Gomella recommends genetic counseling and genomic testing for PCa patients with any of the following:
- more than 2 cases of prostate cancer diagnosed at age 55 or younger in close relatives
- 3 first degree relatives with prostate cancer
- aggressive prostate cancer and more than 2 cases of breast, ovarian, or pancreatic cancer in close relatives[iii]
It’s all in your genes
Biopsy-proven PCa used to be sufficient for treatment decisions based on patient age, PSA, Gleason score and clinical stage. This is no longer true, since these clinical factors alone don’t reveal if a patient’s cell line is one of the roughly 15% of aggressive prostate cancers that don’t behave according to expected growth and progression characteristics. This may help explain why PCa recurs in at least 10% of prostatectomy patients whose surgery gave every indication of “having gotten it all.”
Today, the main interest in genomics is being focused on patients with metastatic PCa that does not respond to androgen deprivation, since various chemotherapies or targeted agents work with some cell lines but not others. Thus, it’s important for oncologists treating metastatic disease to get a molecular portrait of what they’re up against.
However, Dr. Gomella suggests that in 5-10 years, genomic screening and analysis will play a much more active part in matching therapies to primary as well as recurrent PCa. Hopefully, his message is reaching all urologists – and all specialists who are diagnosing and treating PCa.
[i] Ariela Katz. “Clinical Urology Practices Should Include More Genomic Screening for Prostate Cancer.” Targeted Oncology, Dec. 28, 2017.
[ii] “Genomic Testing and Hereditary Prostate Cancer – Interview with Leonard Gomella.” https://www.urotoday.com/video-lectures/lugpa-gu-oncology/video/862-embedded-media2017-11-13-18-50-06.html
[iii] Ariela Katz. Ibid.