How Likely Is Your Prostate Cancer to Return?

Treatment of prostatic cancer by high intensity focus ultrasound

The genes you inherit from your parents determine your body’s appearance, such as eye color and freckles, as well as other characteristics, like blood type and nearsightedness. And that’s not all. Inherited genes also can help determine some of your body’s functional abilities — such as preventing prostate cancer from recurring.

How Prostate Cancer Grows

Androgens (male sex hormones) make prostate cancer grow.

Therefore, androgen deprivation therapy (ADT) is one way to treat prostate cancer, especially when it is advanced or has spread. ADT can involve taking medicines that stop androgen from being produced (in the testicles) or block the effect of androgen throughout your body. ADT also can involve surgically removing both testicles. It’s often used in addition to other prostate cancer treatments, such as radiation therapy or prostate removal.

ADT, in essence, removes the fuel and stops prostate cancer cells from growing — or at least slows them down.

But, in most cases, ADT only works for so long. Prostate cancer cells usually become “castration resistant” eventually. They start making their own androgen, thereby refueling themselves.

Men receiving ADT for prostate cancer have regular prostate-specific antigen (PSA) tests. Rising PSA levels may indicate that prostate cancer has become castration resistant and has begun growing again.

Genes Determine Your Ability to Fight Prostate Cancer

Some men can use ADT to keep prostate cancer at bay longer than others.

A 2016 study at Cleveland Clinic and Mayo Clinic found that men with a certain variant of a specific gene are more likely to get castration-resistant prostate cancer sooner. In these men, ADT doesn’t work as long. Their cancer will recur faster.

Out of 443 prostate cancer patients in the study, all had advanced disease and were treated with ADT. Some men had “normal” HSD3B1 genes — two copies, one from each parent. Others had a variant, HSD3B1 (1245C), but only from one parent. Still others had the variant gene from both parents.

The more copies of the variant gene, the less ADT worked.

Those with “normal” genes in the Cleveland Clinic group of patients stopped prostate cancer from recurring for a median of 6.6 years. The others didn’t fare as well. Those with the variant gene from one parent held off recurrence a median of 4.1 years. Those with the variant gene from both parents held off recurrence a median of only 2.5 years.

Do You Have the Variant Gene?

According to the 1000 Genomes project, about half of U.S. men and women have the HSD3B1 (1245C) gene—from either or both parents.

For now, there isn’t a simple test to identify it (although it can be identified in a full genetic panel). More research is needed before an HSD3B1 (1245C)-based blood test is made widely available.

Why not now? Because there isn’t enough evidence that changing treatment for men with the variant gene would improve outcomes.

We’re doing more research now to see if alternative hormone therapies will work better than ADT in these men. If they do, we’ll have evidence that a simple blood test should be offered to screen for HSD3B1 (1245C).

Personalized Treatment Could Be More Successful

Today we treat all patients with recurring prostate cancer according to a single standard of care. But research could be moving us toward personalizing treatments based on a patient’s genetic characteristics.

In the not-too-distant future, we hope to use genetic testing to determine which patients need which therapy, instead of treating everyone the same.

For example, patients without the HSD3B1 (1245C) gene may fare well with ADT. Those with it may need a more aggressive treatment.

Dr. Sharifi is a medical oncologist at Cleveland Clinic's Taussig Cancer Institute and holds the Kendrick Family Endowed Chair for Prostate Cancer Research at Cleveland Clinic.

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Article Sources
  • Hearn JW, Abuali G, Reichard CA, et al. HSD3B1 and resistance to androgen-deprivation therapy in prostate cancer: a retrospective, multicohort study. Lancet Oncol. 2016;17(10):1435-1444.