Genetics Advance Prostate Cancer Treatment

Statistics show that about 13 out of every 100 men will develop prostate cancer in their lifetime. Not all cases will be fatal, of course. In fact, prostate cancer is among the most survivable types of cancer. Most men will be diagnosed when the cancer is still confined to the prostate, when it’s most treatable. Once diagnosed, however, there are many decisions to be made. For example, when is active surveillance the best approach? What are the pros and cons of various treatments? Is the cancer hereditary? The answers to these questions and more are becoming clearer through genetic testing.

Types of Tests

There are various genetic tests, each with specific goals. A “germline” DNA test assesses a person’s normal DNA (not the DNA from tumors). “Typically a blood test, germline tests are trying to determine if a person has an inherited DNA abnormality that could be responsible for their prostate cancer and might raise their risk for other types of cancer as well,” explains Nicholas Donin, MD, urologic oncologist at UCLA Medical Center. “If a patient has an inherited DNA abnormality, family members need to be alerted and should be tested. All men who have prostate cancer that has metastasized and all men with high-risk prostate cancers are now recommended to undergo this type of testing.”

In contrast, a somatic test (sometimes called a genomic test) evaluates actual cancer cells obtained from a biopsy. The test looks for DNA abnormalities that could be driving cancer growth and helps inform next steps. “Deciding whether to treat prostate cancer or simply undergo surveillance and defer treatment is a very common scenario that many men face,” explains Dr. Donin. “There are several genomic tests that provide information about the tumor’s DNA that can help him make a decision about how to proceed.”

Another common scenario is whether to combine androgen deprivation therapy with radiation therapy. Male hormones, or androgens, help fuel prostate cancer. Androgen deprivation therapy, or ADT, is based on the idea that androgens, such as testosterone, stimulate the growth of cancer cells. Blocking these hormones can slow the cancer’s growth. While ADT is not a cure, it may shrink the tumor to boost effectiveness of radiation treatment or to facilitate surgical removal of the tumor. “There is, however, some uncertainty about which men benefit most from androgen deprivation during radiation therapy treatment,” says Dr. Donin. “Fortunately, we have a genetic test that can provide us with some data and help us to determine who is most likely to benefit from androgen deprivation, and in whom it may not be needed.”

There also are DNA tests that can help determine whether a patient will respond to a particular type of treatment. “For example, men whose prostate cancer harbors mutations in one of the DNA damage repair genes are eligible for treatment with a class of medications called PARP inhibitors,” says Dr. Donin. “These are called ‘predictive’ tests because they can predict who will respond to a particular therapy.”

Ongoing Changes

Dr. Donin points out that genetic testing is a moving target, and what is current clinical practice this year is likely to be out of date next year. Medicare covers many, but not all of these tests.

New Research Findings

While radiation treatment is a very effective therapy for prostate cancer, about one in six men experiences more frequent or painful urination as a lingering side effect. Research led by Amar Kishan, MD, UCLA Chief of Genitourinary Oncology Services developed models that were highly predictive in differentiating between men who would experience toxic side effects after radiation therapy and those who would not. Furthermore, the models were able to predict toxicity radiation type, indicating the models could potentially help with decision-making in choosing one treatment course over the other. The study was published Jan. 2, 2022, in Radiotherapy and Oncology.

Last year at the American Society of Clinical Oncology Genitourinary Cancers Symposium, researchers from the VA Health Care System in La Jolla, CA reported an investigational scoring algorithm that may predict a man’s lifetime risk of developing metastatic or fatal prostate cancer and may help men in deciding whether to undergo prostate cancer screening, researchers report. The study included more than 500,000 male veterans (median age 69) who donated blood for genetic analysis. Compared with men in the lowest 20 percentile of scores, those in the highest 20 percent were nearly 4½ times more likely to die from prostate cancer, 4.18 times more likely to develop metastatic disease, and 5.6 times more likely to develop any prostate cancer, the study found.

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