Prostate Cancer Treatment: What to Do When It Stops Working

If your prostate cancer treatment stops working, there are still several ways to turn this around.

How Does Prostate Cancer Become Resistant to Treatment?

The trouble is that prostate cancer cells are “smart,” she adds. Eventually, they develop workarounds that allow them to keep growing.

Eventually, though, the prostate cancer cells get wise. They sabotage their own receptor to prevent the drug from attaching to it and doing its job. “The cancer cell cuts off the binding site so the drug can't inhibit its growth,” says Channing Paller, MD, an associate professor of oncology at Johns Hopkins Medicine in Baltimore. “And so, the cells are able to keep dividing and making more prostate cancer cells.”

What Happens if Your Prostate Cancer Treatment Stops Working?

The answer to that question today is very different from what it was a couple of decades ago, Paller says. Back then, the only two options were hormone therapy and chemotherapy. Now there are multiple types of hormone therapy drugs with different mechanisms. So as your cancer cells become resistant to one type of drug, your doctor can switch you to another.

• Luteinizing Hormone-Releasing Hormone (LHRH) Agonists These drugs interrupt signals that tell the testicles to produce testosterone. Examples include leuprolide (Lupron, Eligard), leuprolide mesylate (Camcevi), goserelin (Zoladex), and triptorelin (Trelstar).
• LHRH Antagonists These drugs also stop the testicles from producing testosterone, but they do it more quickly than LHRH agonists. Examples include degarelix (Firmagon) and relugolix (Orgovyx).
• Androgen Synthesis Inhibitors These medications block androgen production in other parts of the body. Examples include abiraterone acetate (Zytiga) and ketoconazole (Nizoral).
• Anti-Androgen Drugs This category of drugs block androgens from attaching to proteins called receptors on the prostate cancer cell and helping it to grow. Examples include apalutamide (Erleada), darolutamide (Nubeqa), and enzalutamide (Xtandi).

Once you've taken a certain type of prostate cancer drug, such as a hormone-receptor blocker, chances are you won't see it — or another drug of its type — again.

“Studies have shown that it's probably not beneficial,” Dr. Chatwal says. “We usually recommend switching from one mechanism of action to another. If a patient was on one of the hormone blockers, maybe the next thing we'd switch to would be chemo.”

Genetic Mutations and Targeted Therapy

With no real guidelines on how to order prostate cancer medications, doctors rely on their patients' symptoms and imaging scans to figure out which drug to try next, says Paller. They can also do genomic sequencing to look for gene mutations that can be targeted with specific medications.

The small percentage of men who have an inherited condition called Lynch syndrome may be eligible for immunotherapy once their prostate cancer becomes resistant to hormone therapy and other treatments, says Chatwal.

When Many Treatments Fail

With every new prostate cancer drug tried, the goal is to keep the cancer responding for as long as possible. “Ideally, we're hoping that these drugs will keep things under control without any progression for a year or two years,” Chatwal says.

Yet men who've lived with metastatic prostate cancer for many years could find themselves switching drugs several times, she adds.

Even with the large number of therapies available, after taking one medication after another, eventually some men will reach a point where there are no prostate cancer drugs left to try. Then doctors will usually discuss joining a clinical trial that is testing out a new prostate cancer drug or drug combination.

It can be frustrating to have to switch cancer treatments once or several times. Chatwal stresses the positive: There are a lot more treatment options available for prostate cancer than there are for many other stage 4 cancers. “It's just a matter of working with your doctor and trying to find the right option at the right time," she says.

The Takeaway

• If prostate cancer stops responding to initial hormone therapy, it's time to discuss alternative treatments with your doctor. You may need to switch treatments more than once.
• Consider speaking to a healthcare professional about genetic testing, particularly if prostate cancer runs in your family, to identify any high-risk genes that could influence treatment choices.
• Advancements in cancer treatment mean there are often clinical trials or new medications being developed, providing more options even when other treatments no longer suffice.