What Is Castration-Resistant Prostate Cancer, and How Do You Treat It?

Many medications and other therapies are available to treat prostate cancer. If caught early, there’s almost a 100% survival rate. But if the cancer spreads outside of the prostate gland or if it doesn’t respond to first-line treatments, it can be more complex to manage. 

A specific type of prostate cancer — called castration-resistant prostate cancer (CRPC) — is no exception. Testosterone often helps prostate cancer grow. So prostate cancer is often controlled by lowering the amount of testosterone in the body. This is usually done with medications and sometimes surgery. But if the cancer keeps growing even with low amounts of testosterone, it’s said to be castration resistant. 

Here, we’ll dive into this specific type of cancer and how it’s treated. 

What is castration-resistant prostate cancer?

CRPC is a type of prostate cancer that has stopped responding to treatment that lowers or blocks testosterone. 

The prostate gland is a part of the body that’s important for reproduction. Certain hormones, including testosterone, affect its function and growth. Testosterone helps the prostate mature and grow during puberty. It also causes the prostate to grow throughout adulthood. 

In other words, testosterone is a fuel source that helps the prostate grow. But this fuel supply isn’t specific to normal, healthy cells in the prostate. Testosterone also serves as a possible fuel source for cancer cells. So, if testosterone levels go down, the growth and development of prostate cancer may also go down. 

Surgery and hormone medications are tools that can help lower testosterone levels. This is called castration therapy because it stops the testicles from making testosterone. 

CRPC continues to grow despite castration therapies. It develops after months or years of continued castration therapy.

What are symptoms of castration-resistant prostate cancer?

The symptoms of CRPC are the same as other prostate cancers. People develop CRPC during their treatment for prostate cancer. They may notice that ongoing symptoms are starting to get worse, like:

• Fatigue

• Bone pain

• Trouble urinating

• Weight loss 

Some people don’t notice any new symptoms. They might not realize they’ve developed castration resistance until they have a routine follow-up appointment and find that their cancer is no longer responding to treatment.

Metastatic vs. non-metastatic castration-resistant prostate cancer

CRPC is an advanced form of prostate cancer that is divided into two types:

• Metastatic CRPC: This type of cancer does not respond to hormone therapy and has spread to other parts of the body

• Non-metastatic CRPC: This type of prostate cancer does not respond to hormone therapy but has not spread beyond the prostate. Still, it has the potential to spread to other parts of the body. This type of cancer is becoming less common thanks to advances in prostate cancer treatment. 

If you have non-metastatic CRPC, there’s a chance you won’t need any additional treatment. Depending on your test results over time, your cancer specialist may give you additional medications to help keep your prostate cancer in check.

But if you have metastatic CRPC, your healthcare provider may recommend newer and more powerful forms of:

• Hormonal therapy

• Chemotherapy

• Radioligand therapy

• Immunotherapy

• Other targeted therapies

What is the treatment for castration-resistant prostate cancer?

If you have CRPC, your treatment may look a little different than other types of prostate cancer. Each person’s care plan is a little different depending on their situation. Some treatments you may be offered are listed below.

Hormone medication

CRPC may still respond to different types of hormone medications. Some options include:

• Apalutamide (Erleada): This is a type of hormonal medication. Healthcare professionals call it an antiandrogen. Compared to other hormonal medications, antiandrogen medications use a different strategy to stop testosterone’s effects on prostate cancer. Other hormonal medications try to stop testosterone from being made, but antiandrogens try to stop it from entering the prostate cancer cells. Apalutamide is an oral tablet that’s often taken once daily. 

• Darolutamide (Nubeqa): Like apalutamide, darolutamide is an antiandrogen medication. It’s an oral tablet that’s often taken twice daily. 

• Enzalutamide (Xtandi): Enzalutamide is another antiandrogen medication. It’s an oral pill (tablet or capsule) that’s often taken once a day. 

• Abiraterone (Zytiga): This is also an antiandrogen medication. Abiraterone works slightly differently than other antiandrogen medications, though. Abiraterone is an oral tablet that’s usually taken once a day. 

• Enzalutamide (Xtandi): Enzalutamide is an antiandrogen medication. This is a unique medication: It can be used regardless if CRPC has spread to other parts of the body. If you haven’t tried enzalutamide yet, your cancer specialist may discuss prescribing it to see if it may help. 

Chemotherapy

Chemotherapy is only used to treat advanced forms of prostate cancer. It can improve quality of life and reduce pain. Options include:

• Docetaxel (Taxotere): This is a chemotherapy medication used to kill cancer cells. Docetaxel is given into a vein (IV) every 3 weeks. When used for CRPC, it’s often combined with prednisone, a corticosteroid medication. It may also be combined with other chemotherapy medications. 

• Cabazitaxel (Jevtana): This is a chemotherapy medication. If you didn’t respond well to docetaxel and your cancer specialist thinks chemotherapy may still work, they might discuss trying cabazitaxel. It’s an IV medication that’s often given every 3 weeks. It’s often combined with prednisone.

Immunotherapy

Immunotherapy uses the body’s own immune system to fight cancer. Options include:

• Sipuleucel-T (Provenge): This is an immunotherapy medication. Immunotherapy medications like sipuleucel-T help strengthen your body’s immune system so it can fight cancer more successfully. It’s an IV medication that’s usually given 3 times in a 1-month period. This medication is usually only used if CRPC has spread to the lymph nodes, bones, or lungs and you have little-to-no symptoms. 

• Pembrolizumab (Keytruda): This is an immunotherapy medication. When used for CRPC, pembrolizumab aims to help your immune system fight your cancer if it has many genetic errors. It’s an IV medication that’s usually given every 3 to 6 weeks. Your provider may recommend it if you have specific mutations (called MSI-H or dMMR) and haven’t had luck with other medications. 

Targeted gene therapy

Gene therapy consists of newer treatment options that can help when people have specific genetic changes:

• Olaparib (Lynparza): Mutations (changes) in genes affect certain cancers. Some mutations don’t allow DNA in our cells to repair themselves over time. This can lead to cancer. Olaparib fights CRPC by controlling this type of mutation. Olaparib is an oral tablet that’s usually taken twice daily. You may discuss getting a prescription if you have a specific genetic mutation (called HRRm) and took abiraterone or enzalutamide without success. 

• Rucaparib (Rubraca): This medication is like olaparib. It also aims to stop a genetic mutation that limits DNA’s ability to fix itself. It’s an oral tablet that’s usually taken twice daily. Your provider may recommend it if you have a specific genetic mutation (called BRCA) and took docetaxel or an antiandrogen medication like abiraterone. 

Radionuclide therapy

PSMA-targeted radioligand therapy with Lutetium-177-PSMA-617 (Pluvicto) is a treatment option for some people with metastatic CRPC. This is a newer option and more people may qualify for this therapy as time goes on. 

Radium-223 (Xofigo) is a radiation-based medication. It works by using energy to kill cancer cells. It’s an IV medication that’s often given every 4 weeks. This medication can help improve survival chances if CRPC has spread to the bones. 

Surgery

Some people opt for surgery as part of their treatment plan. Surgery doesn’t treat the cancer directly. But it can help reduce urinary symptoms from cancer like trouble urinating. This can improve quality of life. 

Is castration-resistant prostate cancer curable?

There’s no cure for metastatic CRPC.

Medication effectiveness rates for CRPC vary by person. A medication’s exact effectiveness depends on your cancer, its severity, and other medications you’ve tried. It’s hard to predict how well a medication may work. 

But a few studies help show how treatable CRPC is. Cancer treatments in these studies are often judged by how long they can help people survive. They’re also judged by how long they can help cancer stay the same before it gets any worse. 

In general, the prognosis of people with CRPC can vary widely. In people without metastases, but a fast PSA doubling time, survival may range from 3 to 7 years. In people with metastatic CRPC, survival can range from 1 to 7 years, depending on a range of factors. This includes symptoms, where the cancer has spread, and your response to therapy. 

But more and more effective therapies are becoming available, so many older studies are becoming out of date. Most approved therapies can improve survival by 20% to 40%, compared to no treatment or older therapies. 

If you have CRPC and are curious how likely your medication is to work, speak to your cancer specialist. Based on your specific situation and treatment, they can give you a more precise answer. During this time, it’s critical that you monitor your bone health and any other medical conditions you may have. You should also follow a heart-healthy diet and exercise for overall good health. 

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Written by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Edited by:

Patricia Pinto-Garcia, MD, MPH

Patricia Pinto-Garcia, MD, MPH, is a medical editor at GoodRx. She is a licensed, board-certified pediatrician with more than a decade of experience in academic medicine.

Reviewed by:

Brandon R. Mancini, MD, MBA, FACRO

Brandon R. Mancini, MD, MBA, FACRO, serves as medical director at BAMF Health in Grand Rapids, MI, in the emerging field of theranostics. His clinical focus is treating people with metastatic prostate and neuroendocrine cancers.

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