Metastatic castration-resistant prostate cancer (mCRPC) is an advanced form of prostate cancer. Metastatic means the cancer has spread from the prostate to other parts of the body, like the bones, liver, or lungs. This makes the disease harder to treat since it’s no longer just in one place.

“Castration-resistant” means the cancer keeps growing even when testosterone levels are very low. Testosterone is a hormone that helps prostate cancer grow, so doctors usually treat prostate cancer by lowering or blocking this hormone.

However, in mCRPC, the cancer cells find ways to survive and grow without it. This makes the disease more difficult to control, and a healthcare team needs to use other treatments to try to slow it down and reduce symptoms.

What Is Metastatic Castration-Resistant Prostate Cancer?

Prostate cancer starts in the prostate, a gland that helps make semen. If it is localized, the cancer may be monitored or may be treated with surgery or radiation therapy.

Another treatment for prostate cancer is to decrease the amount of testosterone in the body, called androgen-deprivation therapy (ADT). This may be done with medications (chemical castration). Surgical removal of the testicles (which produce testosterone) may also be used to reduce testosterone in some cases.

In mCRPC, the cancer grows beyond the prostate and keeps growing even when testosterone levels are very low. Castration resistance can happen for many reasons. The cancer cells may change (mutate) or find other ways to grow without testosterone. This makes treatment more difficult.

When prostate cancer is both metastatic and castration-resistant, the cancer becomes more difficult to treat.

Symptoms may include:

• Blood in the urine
• Bone pain
• Fatigue
• Painful urination
• Shortness of breath
• Trouble urinating
• Weight loss

Prognosis and Life Expectancy

Treatments help some people live longer with mCRPC, including newer hormone medicines, chemotherapy, and other therapies. But even with these treatments, mCRPC is still not curable.

A study published in 2024 of people diagnosed with mCRPC from 2014 to 2019 found a median survival of a little over two years (25.6 months) from the time of their diagnosis.

Doctors use special tools to help determine how serious the cancer is. Two important ones are the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) criteria and LATITUDE criteria.

The CHAARTED study looked at the volume in which the cancer had spread. People with a lot of cancer in their bones (four or more spots, including at least one outside the spine or hips) or in organs like the liver had a worse outlook.

The LATITUDE study looked at three things: if a person had three or more bone spots, a high Gleason score (which shows how aggressive the cancer is), and cancer in organs. If a person had two or more of these, they were seen as high risk and less likely to live as long.

These tools help providers plan the best treatments. But it’s important to know that everyone is different. A person’s age, health, and how their cancer responds to treatment make a difference.

Current and Emerging Treatments

Over time, treatments for mCRPC have advanced. Years ago, once the cancer stopped responding to hormone therapy, there were few options left. Used even in the disease’s advanced stages, chemotherapy was one of the first treatments to prolong life.

Later, new types of hormone therapies were developed that could work even when testosterone levels were already very low. Other treatments, like immunotherapy and radiation, were developed to help manage symptoms and improve quality of life.

Hormone Therapy

Newer hormonal treatments for mCRPC are available to help treat the disease. These medications work to further lower the amount of hormones like testosterone made in multiple areas of the body or by blocking hormones from being able to get into the cancer cells.

Treatments like abiraterone and enzalutamide are commonly used medications in this category:

• Zytiga (abiraterone) helps lower the level of testosterone
• Xtandi (enzalutamide) works by blocking the hormone’s effect on cancer cells so these cells have a harder time growing and spreading

Other newer treatments are Erleada (apalutamide) and Nubequa (darolutamide). These drugs work very similarly to Xtandi by blocking the signals that tell cancer cells to grow. They are being made to be even more effective and have fewer side effects for some people.

Chemotherapy

Chemotherapy can help slow down the cancer and improve symptoms. Two important chemotherapy drugs used for mCRPC are docetaxel and cabazitaxel.

Taxotere (docetaxel) is usually the first chemotherapy drug administered for mCRPC. It works by stopping cancer cells from growing and dividing.

People get docetaxel through an intravenous line (IV), usually every three weeks. This medicine doesn’t cure the cancer, but it can help people live longer and feel better by shrinking tumors and easing pain caused by the cancer.

If docetaxel stops working or causes too many side effects, oncologists (medical doctors who diagnose and treat cancer) may try a different drug called Jevtana (cabazitaxel). It works similarly but can be helpful when the cancer no longer responds to docetaxel. Like docetaxel, cabazitaxel is given through an IV and can slow the cancer’s growth.

Both of these chemotherapy drugs can have side effects, such as tiredness, nausea, or a decrease in blood cell counts. Still, oncologists (cancer specialists) carefully watch the person and give other medicines to help with these problems.

Immunotherapy

Immunotherapy is a treatment that helps the body’s immune system fight cancer. One immunotherapy option for mCRPC is Provenge (sipuleucel-T).

Sipuleucel-T is different from other treatments because it is made individually for each person. First, some of the person’s immune cells are taken from their blood. Then, those cells are sent to a special lab where they are trained to recognize prostate cancer.

These trained cells are then infused back into the person’s body through an IV. Once inside, these cells help the immune system attack the prostate cancer. It works best for people who have few or no symptoms and whose cancer is not growing very quickly.

Radiotherapy

Radiation therapy is a treatment that uses high-energy rays to kill cancer cells. For mCRPC, radiation therapy is often used when the cancer has spread to the bones.

When prostate cancer spreads to the bones, it can cause pain, swelling, or even broken bones. Radiation can help by shrinking the tumors in the bone, which can relieve pain.

In some cases, oncologists may also use a special type of radiation called radium-223. This medicine goes into the bloodstream and travels to the bones where the cancer is located. It gives off tiny amounts of radiation directly to the cancer cells in the bone, without hurting too much of the healthy tissue around it.

Targeted Therapies

Targeted therapy is a newer kind of cancer treatment that finds and attacks specific parts of cancer cells without harming too many healthy cells. They are only used if the cancer has specific characteristics.

Poly (ADP-ribose) polymerase (PARP) inhibitors: These are used for people whose prostate cancer cells have mutations in certain genes, like BRCA1 or BRCA2. These gene changes make it harder for the cancer cells to repair themselves. PARP inhibitors block a tool the cancer cells use to fix their DNA, so the cells get weaker and die.

PARP inhibitors approved by the Food and Drug Administration (FDA) for mCRPC are:

• Akeega (niraparib and abiraterone)
• Lynparza (olaparib)
• Rubraca (rucaparib)
• Talzenna (talazoparib)

Prostate-specific membrane antigen (PSMA)-targeted therapy: PSMA is a protein found on most prostate cancer cells. Pluvicto (lutetium Lu 177 vipivotide tetraxetan) is made to find PSMA and deliver radiation to the cancer cells. This helps kill the cancer while leaving most healthy cells alone.

Enrolling in a Clinical Trial

People volunteer for clinical trials to try new medicines or therapies that may not yet be available to everyone. These trials help determine if a new treatment is safe, if it works, and what side effects it might have.

Many clinical trials are underway for people with mCRPC. Some are testing new types of targeted therapy, immunotherapy, or new ways to use radiation. Others are trying to combine different treatments to see if they work better together. These new treatments could help people live longer, feel better, or have fewer side effects.

A medical team closely watches people who join a trial to ensure their safety. The results of these studies help improve care for future patients.

How Genetic Testing Can Help

Genetic testing examines a person’s or cancer cells’ DNA to find changes, or mutations, in certain genes. For people with mCRPC, genetic testing is becoming more important. It can help oncologists learn more about how the cancer works and which treatments might help the most.

Some of the most important genes examined are BRCA1 and BRCA2. These genes usually help fix damaged DNA. But if there are changes (mutations) in these genes, cancer cells can grow and spread more easily. A person with mCRPC who has a BRCA mutation may be able to get a PARP inhibitor.

Other gene changes can affect treatment. For example, some cancers have problems with genes that help with DNA repair or have changes in what is called mismatch repair or microsatellite instability. If a cancer has these changes, the person might be able to get certain immunotherapy medications, which help the body’s own immune system fight the cancer.

End-of-Life Care and Support

When someone with mCRPC reaches the final stages of the illness, the focus changes to end-of-life care. This type of care helps ensure the person is as comfortable as possible and supports both their body and mind.

Hospice care focuses on comfort care without curative treatments at the end of life. It helps the person and their family. Hospice teams include doctors, nurses, social workers, and spiritual helpers who work together to provide care at home or in a facility.

One important part of end-of-life care is symptom management. People with mCRPC may have pain, feel very tired, have trouble urinating, or lose their appetite. Some may feel weak or have trouble breathing.

Pain medicine, antinausea drugs, and treatments for shortness of breath can help the symptoms. The goal is to help the person feel better and enjoy their time with family and friends.

Another important part of care is emotional and psychological support. Living with advanced cancer can be scary and stressful. People may feel sad, anxious, or worried about what’s next. Talking to a counselor or therapist, or communing with others in a support group, can help. Some people also find comfort in spending time with loved ones or doing simple things they enjoy.

Summary

Metastatic castration-resistant prostate cancer (mCRPC) is a complex and serious condition, but doctors and scientists are making progress every year. While it is not yet curable, treatment options are available. These include advanced hormone therapies, chemotherapy, immunotherapy, radiation, targeted therapies, and supportive care.

Genetic testing can also help guide treatment choices. Clinical trials are helping test even more new treatments, giving hope for better results in the future. Each person’s journey with mCRPC is different. Having the right information and support can make a big difference in managing the disease and maintaining their quality of life.