Why Do PTEN Mutations Matter In Prostate Cancer?

PTEN acts like one of the body’s natural brakes on cell growth. It helps control how cells divide and prevents abnormal growth. When PTEN is functioning normally, it keeps prostate cells from growing out of control.

A PTEN mutation, or PTEN loss, means this protective gene is no longer doing its job. As a result, cancer cells may grow faster and more aggressively.

“When you have a mutation in PTEN, you lose the brake — and then cancer starts to grow more aggressively,” Dr. Shirin Razdan, a urologist who specializes in robotic surgery at HCA Florida Healthcare, tells SurvivorNet.

Doctors may use terms like PTEN loss, deletion, or deficiency, all of which describe the same underlying issue.

PTEN abnormalities are relatively common in prostate cancer, especially in higher-grade, locally advanced, or metastatic disease. They tend to appear more often as the cancer becomes more aggressive.

How Does PTEN Loss Affect Treatment?

PTEN loss is generally considered a higher-risk feature and may be associated with a greater chance of cancer growth or spread. However, it is only one part of the overall picture.

Doctors also consider factors like PSA levels, Gleason score, imaging results, and cancer stage when assessing prognosis. PTEN helps provide insight into how the cancer behaves but does not determine outcomes on its own.

PTEN loss may lead doctors to recommend a more proactive or intensified treatment approach.

“In men who have this mutation, they may be candidates to receive targeted therapy in addition to hormone treatment, with improved outcomes,” Dr. Razdan says.

Even when PTEN loss is detected, it does not always change immediate treatment decisions, especially in patients with earlier-stage disease who are already expected to do well with standard therapies. PTEN testing is more commonly considered in patients with advanced or metastatic cancer, where understanding the biology of the tumor may have a greater impact on how aggressively doctors choose to treat it.

An ongoing phase III clinical trial, the CAPItello-281 trial, is evaluating whether a specific type of targeted therapy (capivasertib, brand name Truqap) is an option for metastatic prostate cancer patients with PTEN deficiency.

“In men who have this specific mutation in PTEN, they might be a candidate to receive this medication in addition to hormones … with improved survival,” Dr. Razdan says. “The question then becomes … can we give this medication or targeted agents before cancer becomes metastatic? If we know you have an aggressive cancer based on final prostatectomy pathology … can we give you an agent that slows the growth of the cancer and prevents progression, either local or metastatic?”

A Move Towards ‘Personalized’ Medicine

PTEN is one of several biomarkers that doctors may evaluate when planning treatment.

“PTEN is just one of many genes we test for, either in the tumor or through genetic panels, to understand what treatments a patient may respond to,” Dr. Razdan notes.

“This is part of what we now call personalized medicine, matching the right treatment to the biology of each patient’s cancer.”

While PTEN loss can be detected through genetic or molecular testing, it is typically considered a “tumor-only mutation.” This means it is not inherited, and family members do not need to be tested.

However, if there is a strong family history of cancer, genetic counseling may still be recommended.

Questions To Ask Your Doctor

• Have I/can I undergo molecular testing?
• Which mutations have I been tested for? Is PTEN included?
• How will the results of this testing affect my treatment options?
• Am I eligible for any targeted therapies based on my molecular testing results?

Learn more about SurvivorNet's rigorous medical review process.

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