As the role of genetic testing in clinical practice becomes more prevalent for prostate cancer patients to identify mutations, physicians must consider a variety of factors to determine which patients are candidates for somatic testing and /or germinal.
As the role of genetic testing in clinical practice becomes more prevalent in patients with prostate cancer to identify mutations, physicians must consider a variety of factors to determine which patients are candidates for somatic testing and/or germlines, according to Emmanuel Antonarakis, MD.
In an interview with Live®, Antonarakis, professor of medicine and associate director for translational research at the Masonic Cancer Center at the University of Minnesota, Minneapolis, discussed somatic and germline testing recommendations and therapeutic agents used for patients with genetic mutations. . He also previewed his upcoming presentation on genetics at the Large Urology Group Practice Association (LUGPA) conference taking place November 10-12, 2022 in Chicago, Illinois.
Live®: What main points do you want your colleagues to take away from your presentation?
Antonarakis: Genetic and genomic testing are now part of the clinical practice of urologists, medical oncologists and radiation oncologists [who are] manager [patients with] Prostate cancer. I’m going to cover some basics and go over them for the audience. What is a germline mutation? What is a somatic mutation? Why are these germline and somatic mutations relevant to genetic counseling and therapeutic considerations? What kind of patients should be tested for germline and somatic mutations and why testing these patients is important [and] how does it inform our clinical practice? I will also finish [the talk] with 2 caveats on interpreting a genetic test report that can be confusing for some people and how to overcome the caveats.
How can patients benefit from genetic testing?
I would separate prostate cancer into 2 main stages: patients with localized, potentially curable disease [disease] and metastatic patients [disease] which are usually managed with systemic therapies but may not be cured. For an audience of urologists, many patients they will see [have] localized, potentially curable patients, and for them we need to separate the need for germline and somatic testing.
Germline testing for a patient with localized prostate cancer is generally recommended by many oncology and neurology guidelines for patients who have high-risk localized disease or those with positive pelvic lymph nodes. In addition, some patients have localized low- or very-low-risk prostate cancer, and guidelines generally do not necessarily recommend germline genetic testing for these patients; the exception is for those with a family history of prostate cancer or other cancers or for those with genetic background that could increase the risk of having 1 of these germline mutations.
The somatic mutation part is easy because for patients with localized prostate cancer, even those with pelvic lymph node disease, somatic testing is generally not recommended as there is no intervention therapy based on somatic genetic information in this context.
To close patients with metastatic disease, germline and somatic genetic testing is recommended for these patients mainly because of the therapeutic implications where we have at least 2 classes of drugs that can target certain genetic alterations and to advise the patient on the his family’s risk of prostate and other cancers.
How often are genetic tests currently used in practice and should there be increased use in clinical practice?
In practice, genetic testing is variable and depends on where genetic testing is performed or considered. In medical oncology clinics, especially in university medical oncology clinics, this is done quite commonly. I would say that over 50%, ideally over 75%, of patients will undergo both germline and somatic testing. In urology clinics, it depends on the practice and provider.
Many urologists in large group practices perform germline testing, especially for their high-risk, very high-risk, or lymph node-positive patients. This could be expanded to encompass the 4 guideline recommendations that all patients with high-risk, very high-risk, or locally advanced prostate cancer should undergo germline testing. There are many urology clinics and some oncology clinics in this country where patients do not undergo germline testing as per the guidelines. We should all do our part to educate and increase the frequency of genetic testing for patients who are appropriate for testing.
How has genetic testing contributed to treatment decisions and prostate cancer so far?
Currently, there are at least 2 classes of therapeutic agents that are used for patients with certain germline or somatic genetic mutations. The first one [are] PARP inhibitors. These are drugs like olaparib [Lynparza] and rucaparib [Rubraca].
We have 2 FDA approvals for these drugs in metastatic castration-resistant prostate cancer. For patients who have mutations in genes, such as BRCA1 and BRCA2there is a slight complexity in the fact that olaparib is approved for a total of 14 gene mutations, whereas rucaparib is currently only approved for 2 genes, BRCA1 and BRCA2.
The second class of agents that have made their way into the therapeutic arsenal are PD-1 inhibitors, drugs like pembrolizumab [Keytruda], for patients with prostate cancer who have a mismatch repair deficiency, sometimes referred to as microsatellite instability. For these patients, their tumors are highly immunogenic, meaning they respond more favorably to immune checkpoint agents, especially pembrolizumab, and this is an option for patients with metastatic prostate cancer. castration resistant.
What is the main lesson you hope to pass on to your colleagues?
[A] The main takeaway is to at least consider doing germline genetic testing in the vast majority of patients with prostate cancer. The only ones you don’t have to see are patients with low or very low risk prostate cancer, no family history of cancer, and no Ashkenazi Jewish heritage. For the rest, at least germline testing should be done, and for all patients with metastatic prostate cancer, there are 2 therapeutic indications for getting somatic genetic testing and it should be done for any patient.
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