What to Expect With Advanced Prostate Cancer Treatment

Is it working? The drug is still being studied, but research is promising.  A study showed a drop in blood levels of prostate-specific antigen (PSA), a prostate cancer tumor marker, in people who took it. One-quarter of people in the study whose tumors could be measured saw shrinkage on scans. These may be signs that it is working. 

What are the side effects? Xaluritamig could trigger these symptoms:  

• An immune system storm known as Cytokine release syndrome
• Fatigue 
• Muscle aches and pains

Hormone Therapy

Male sex hormones, namely testosterone, can cause prostate cancer to grow and spread. Hormone therapy can block or blunt these effects. Hormone therapy is the main treatment for metastatic castration-sensitive prostate cancer. It is not a cure, and people progress to “hormone-refractory or androgen-independent prostate cancer.”

There are several types of hormone therapy that can be used to treat advanced prostate cancer, including:  

LHRH agonists 

Luteinizing-hormone releasing hormone (LHRH) agonists — also called gonadotropin-releasing hormone (GnRH) analogues — include leuprolide, goserelin, and triptorelin. 

Why is it taken? These medications suppress production of the male sex hormone testosterone by your testicles. They are sometimes called medical castration because they lower testosterone levels as well as testicle-removing surgery does. 

How is it taken? These drugs are injected or placed as small implants under the skin from once a month up to once every six months.

LHRH antagonists

LHRH antagonists (also known as gonadotropin-releasing hormone (GnRH) antagonists) work slightly differently than LHRH agonists. They bind to testosterone receptors in the pituitary gland. That prevents the secretion of luteinizing hormone and stops your testicles from producing male sex hormones. Unlike LHRH agonists, LHRH/GnRH antagonists do not cause a testosterone flare. They include: 

• Degarelix (Firmagon)
• Relugolix (Orgovyx) 

Why are they taken? LHRH antagonists can help treat advanced prostate cancer. They may be a better option than LHRH agonists  if you have a history of or high risk for heart disease.  

How are they taken? Degarelix (Firmagon) is a shot, and relugolix (Orgovyx) is a pill. 

Are they working? Your doctor will test your blood levels of PSA after a few months of treatment. A lower level is a good sign that treatment is working. (Note: Sometimes testosterone levels rise briefly after starting an LHRH agonist, and then drop to very low levels. This does not happen with LHRH antagonists.)

Anti-androgens 

Anti-androgens are another type of hormone therapy used to treat advanced prostate cancer. 

First-generation anti-androgens are most often used with treatments that lower testosterone levels. They include:

• Bicalutamide
• Flutamide
• Nilutamide

Next-generation anti-androgens may be offered when your cancer is no longer responding to other forms of hormone therapy. They include:

• Apalutamide
• Darolutamide
• Enzalutamide     

Why are they taken? The first-generation anti-androgen drugs block the effects of testosterone in the body. The next-generation anti-androgens block the effects of androgens on cancer cells more strongly and more specifically than older versions. 

How are they taken? The first-generation and next-generation anti-androgen drugs are pills taken every day.

Are they working? You should undergo follow-up exams within six months after starting therapy, including PSA blood tests, to see how well the anti-androgen therapy is working.

What are the side effects? Anti-androgen treatments may cause:

• Hot flashes
• Mood swings
• Low sex drive
• Erectile dysfunction
• Heart problems
• Brittle bones
• Low muscle mass

Androgen synthesis inhibitors 

Androgen synthesis inhibitors, including abiraterone (Yonsa, Zytiga) are an even newer category of hormone therapy that may be used to treat advanced prostate cancer. They block an enzyme called CYP17, which helps stop cells from making male sex hormones in the testicles, adrenal glands, and prostate cancer cells.  Like abiraterone, an older antifungal medication called ketaconazole also keeps the adrenal glands from producing male hormones. 

Why are they taken? These drugs lower testosterone levels to a greater extent than any other known treatment. They may also be used if your prostate cancer is considered high risk and has started to spread to the bones or the organs. They’re also used if a cancer is still growing despite low testosterone levels from another hormone therapy.

How are they taken? These are taken as pills. (Ketoconazole is not approved for prostate cancer but is sometimes used off-label to treat it.)

Are they working? Your doctor will measure your blood PSA levels after a few months of treatment to see if it has gone down.

What are the side effects? Androgen synthesis inhibitors may cause:

• Diarrhea
• Itching
• Rash
• Fatigue
• Erectile dysfunction
• Liver damage

Chemotherapy

Chemotherapy works by killing all fast-growing cells in the body. Cancer cells divide rapidly, but so do many other types of cells. That’s why there is often collateral damage with chemotherapy, such as hair loss and nausea.

Why is it taken? Chemotherapy may be used to treat advanced prostate cancer that has spread. It can be used with hormone therapy or on its own if hormone therapy is no longer working.

Docetaxel is the standard chemotherapy for advanced prostate cancer. It is usually given with a steroid to offset some side effects. Other chemotherapy drugs that may be used to treat advanced prostate cancer include: 

• Cabazitaxel
• Carboplatin
• Estramustine
• Mitoxantrone 

Cabazitaxel may be used if you progressed during or after treatment with docetaxel. It is also used in combination with the steroid prednisone.

How is it taken? Chemotherapy drugs are given via an intravenous infusion. Dosing schedules depend on the drug.

Is it working? Chemotherapy is working if there’s at least a 50% decline in blood PSA levels four weeks after treatment.

What are the side effects? Chemotherapy may cause:

• Nausea
• Hair loss
• Drop or halt of blood cell formation
• Tingling, numbness, or pain in the fingers or toes
• Fluid build-up

Precision Medicine

Precision or personalized medicine for advanced prostate cancer tailors treatment to you based on the specific genetic profile of your tumor. Some prostate tumors show mutations in genes, such as the breast cancer genes BRCA1 and BRCA2. Mutations in the BRCA2 gene are the most common. Poly (ADP-ribose) polymerase (PARP) inhibitors are a type of precision medicine that can help treat these cancers.

Why is it taken? Precision medicine may be used if your tumor has a specific genetic makeup. Research is looking at using these drugs before and after surgery, combining them with hormone therapy, radiation, chemotherapy, or other types of treatments.

How is it taken? PARP inhibitors are pills.

Is it working? Your health care team will run regular blood tests, X-rays, and different types of scans to see whether the treatment is working.

What are the side effects? Some types of PARP inhibitors may increase your risk of leukemia, but this is rare. Precision medicine, such as PARP, may cause:

• Fatigue
• Bleeding
• Infections
• Nausea
• Vomiting
• Stomach pain
• Diarrhea
• Constipation
• Unexplained weight loss
• Dizziness
• Headaches

Radiation Therapy and Radiopharmaceuticals

Radiation uses high-energy beams such as X-rays to kill tumors. Radiopharmaceuticals are radioactive drugs. They deliver radiation that kills prostate cancer cells found in various regions of the body. Radiopharmaceuticals may be an option to treat advanced prostate cancer that has been previously treated with hormone therapy and has a protein called prostate specific membrane antigen (PSMA) present on the cancer cells. A PSMA PET scan can be performed to see if the cancer cells have PSMA.

Radiopharmaceuticals used for prostate cancer that has spread to the bones include:

• Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) is a radiopharmaceutical that attaches to PSMA found on the surface of prostate cancer cells and then delivers radiation inside of the cancer cells. 
• Radium-233 (Xofigo) is sometimes used to treat prostate cancer that has spread only to the bones. It may increase overall survival with certain types of prostate cancer.
• Strontium-89 chloride (Metastron)
• Samarium-153 (Quadramet)

Why is it given? If prostate cancer has spread to the bones, radiation and radiopharmaceuticals can help reduce pain or stave off fractures. It may also be an option if your cancer comes back after surgery. 

How is it given? Radiation to the prostate gland is given via a machine placed outside the body. Radiopharmaceuticals are given by infusion into the veins usually every six weeks for up to six doses.

Is it working? Your doctor will monitor PSA levels and perform scans to see if the therapy is working. Following radiation therapy, your PSA will fall, but it will not reach its lowest value immediately after treatment. 

What are the side effects? Your doctor may recommend limiting close contact with people for several days after treatment due to the radiation present in your body from the treatment.

Radiation therapy may cause:

• Increase in the frequency and urgency of urination
• Other urinary issues
• Diarrhea
• Erectile dysfunction
• Increased frequency of bowel movements
• Worsening of hemorrhoids or rectal irritation

Radiopharmaceuticals may cause: 

• Fatigue
• Nausea
• Dry mouth
• Decrease in red blood cell count
• Decrease in white blood cell count
• Decrease in platelet count

Ablative Therapy

Ablative therapy uses various methods, such as extreme heat or cold, to ablate (destroy) cells. Ablative therapy can target the entire prostate gland or only where the cancer lurks (focal therapy).

Why is it taken? Ablative therapy may be an option in advanced prostate cancer after radiation therapy is used if the cancer has come back.

How is it taken? Ablative therapy is not a medication. It’s a variety of surgeries: 

• Cryotherapy delivers a freezing solution into tumor cells to kill them.
• High-intensity focused ultrasound (HIFU) is a surgery that combines the sound waves of an ultrasound and the guidance of magnetic resonance imaging (MRI) to generate high heat to kill cancer cells.
• Irreversible electroporation uses electric current to create tiny holes in tumor cells. The procedure is focused to kill only cancer cells and avoid the surrounding tissues.

Is it working? Your doctor will suggest testing such as magnetic resonance imaging (MRI) and prostate needle biopsy to see if ablation therapy is working.

What are the side effects?  The risks of long-term urinary incontinence and erectile dysfunction are likely lower with ablation surgery than radiation therapy. Side effects after surgery may be worse if you’ve already had radiation therapy. They include: 

• Pain in the treatment area
• Blood in the urine
• Urinary tract infections
• Trouble urinating

Bone-Targeted Therapy

Bisphosphonates, such as zoledronic acid, slow the turnover of bone cells (osteoclasts). The bone cells can become overactive in prostate cancer that has spread to the bone. Denosumab blocks osteoclasts, too, but in a different way than bisphosphonates. 

Why is it taken? Bone-targeted therapy may be an option if your prostate cancer has spread to your bones, causing fractures, pain, and other problems. These therapies, which include bisphosphonates and denosumab, may also be an option if hormone therapy is not working. 

How are they taken?  Bisphosphonates can be taken as pills or given as an infusion. Denosumab is given via injection.

Are they working? Your doctor will schedule regular follow-ups, including blood tests and imaging scans, to see how your bones are responding. Cancer that has spread to the bones can be painful, so a reduction in pain can also be a sign that treatment is working.

What are the side effects? Osteonecrosis of the jaw, the loss or breakdown of part of the jaw, is a rare but serious side effect seen with this class of drugs. It can cause pain that is difficult to treat. Bisphosphonates may cause flu-like symptoms, bone or joint pain, or kidney problems. Denosumab may cause:

• Flu-like symptoms
• Bone or joint pain
• Nausea
• Weakness
• Fatigue