Treatment Update: Prostate Cancer

Localized or Locally Advanced Prostate Cancer

The most common treatment approaches for men with localized or locally advanced prostate cancer are:

Active surveillance for localized, low-grade prostate cancer (in which the cancer cells look similar to healthy cells). Close monitoring of the status of the prostate cancer through regular office visits and medical tests, including measuring PSA (prostate specific antigen). PSA is a substance produced by the prostate gland which may indicate the presence of cancer.

Surgery. In a prostatectomy, the prostate and nearby tissue is removed, which may include seminal vesicles and lymph nodes.

Cryotherapy. This approach involves the freezing of the tumor to kill cancer cells.

Radiation therapy, which is the use of radiation to kill cancer cells in the prostate. Brachytherapy, in which radioactive material is placed inside the body, is one type of radiation therapy that’s used to treat prostate cancer.

Hormonal therapy may also be given before, during and after radiation therapy. See the next section, “Metastatic Prostate Cancer,” for information on hormonal therapy.

Metastatic Prostate Cancer

Treatments are available for metastatic prostate cancer that can stop cancer growth, control pain and other symptoms and extend survival.

Hormonal therapy. Also called androgen deprivation therapy (ADT), hormonal therapy remains the mainstay for treating metastatic prostate cancer. This type of treatment is aimed at reducing the levels of male hormones (androgens) in the body, or stopping them from affecting prostate cancer cells. The main androgens are testosterone and DHT; they act like a fuel, encouraging prostate cancer to grow. Without androgens, prostate cancer goes into remission, often for many years. (Remission is when all signs and symptoms of cancer disappear.)

Surgery as a form of hormonal therapy. Another way to stop the production of male hormones is an orchiectomy, a surgical procedure in which the testicles are removed. The removal of the testicles causes most prostate cancers to stop growing or to shrink.

Chemotherapy and other treatments. Doctors sometimes recommend chemotherapy as a treatment for hormone-resistant metastatic prostate cancer. One chemotherapy drug is usually given, rather than multiple drugs being given in combination. The drugs typically used are docetaxel (Taxotere) and cabazitaxel (Jevtana).

Combining hormonal therapy with chemotherapy and androgen receptor signaling inhibitors (ARSIs). Depending on the man’s individual circumstances, it is now a standard treatment to give the chemotherapy docetaxel in conjunction with hormone therapy as a first line treatment approach. For men with newly diagnosed metastatic disease, treatment options include:

• ADT alone
• Docetaxel in combination with ADT
• The combination of abiraterone, prednisone and ADT
• The combination of enzalutamide and ADT
• The combination of apalutamide and ADT
• The combination of abiraterone, prednisone, ADT and docetaxel
• The combination of darolutamide, ADT and docetaxel

Abiraterone, enzalutamide, apalutamide and darolutamide are described below. Prednisone is a corticosteroid that controls inflammation.

Other treatment options. A number of other types of drugs have been approved by FDA for metastatic prostate cancer that is no longer responding to hormonal therapy or chemotherapy. These drugs include:

• Sipuleucel-T (Provenge). This medication, an immunotherapy, works by using the body’s own specialized white blood cells (important parts of the body’s immune system) to destroy prostate cancer cells. Sipuleucel-T is used in treating men with asymptomatic or minimally symptomatic prostate cancer that is resistant to hormonal therapy.

• Abiraterone (Zytiga). Abiraterone blocks an enzyme called CYP17, helping to stop these cells from producing male hormones. It is used with the corticosteroid prednisone.

• Enzalutamide (Xtandi). Male hormones can attach to prostate cancer cells, helping them to grow. Enzalutamide blocks this from happening, slowing the growth of (or destroying) prostate tumors.

• Radium Ra 223 (Xofigo). Radium Ra 223 is a bone-seeking radioisotope, a drug that contains a radioactive therapy. Approved for the treatment of symptomatic prostate cancer, this drug is injected into the bloodstream and seeks out prostate cancer cells that have spread to the bone.

• Apalutamide (Erleada). In September 2019, the FDA approved apalutamide, an anti-androgen drug that blocks male hormones from attaching to prostate cancer cells, which can slow the growth of (or destroy) prostate tumors. Apalutamide was initially approved in 2018 for treatment of non-metastatic, hormonal therapy-resistant prostate cancer.

• Darolutamide. In August 2022, the FDA approved darolutamide (Nubeqa) in combination with docetaxel for the treatment of metastatic hormone-sensitive prostate cancer.

• Rucaparib (Rubraca) and olaparib (Lynparza). In May 2020, the FDA approved rucaparib and olaparib for the treatment of prostate cancer in men with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). Both these drugs are PARP inhibitors, which destroy cancer cells by preventing them from repairing their damaged DNA.

• Relugolix (Orgovyx). Approved by the FDA in January 2021, relugolix is an oral hormonal agent that reduces testosterone levels in men with advanced prostate cancer.

• Lu 177 vipivotide tetraxetan (Pluvicto). In March 2022, the FDA approved lu 177 vipivotide tetraxetan for the treatment of prostate-specific membrane antigen positive mCRPC that was previously treated with an anti-androgen drug and taxane-based chemotherapy. Lu 177 vipivotide tetraxetan combines a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle).

• Newer combination treatments:

• In May 2023, the FDA approved olaparib (Lynparza) with abiraterone (Zytiga) and prednisone for the treatment of BRCA-mutated mCRPC.

• In June 2023, the FDA approved talazoparib (Talzenna) with enzalutamide (Xtandi) for the treatment of HRR gene-mutated mCRPC.

• In August 2023, the FDA approved a dual action tablet containing niraparib and abiraterone acetate (Akeega) with prednisone for the treatment of BRCA-mutated mCRPC.

All cancer treatments can cause side effects. It’s important that you report any side effects that you experience to your health care team so they can help you manage them. Report them right away— don’t wait for your next appointment. Doing so will improve your quality of life and allow you to stick with your treatment plan. It’s important to remember that not all people experience all side effects, and people may experience side effects not listed here.

Side Effects of Hormonal Therapy

The side effects of hormonal therapy in the treatment of prostate cancer can include mild anemia, fatigue, changes in cholesterol, mood changes, loss of sexual thoughts and erectile dysfunction. There is also an increased risk of cardiovascular events in men with pre-existing risk factors, such as high cholesterol or prior heart attacks.

Additional potential side effects:

• Hot flushes. There are medications that can help if hot flushes occur, such as certain types of antidepressants or low doses of female hormones (estrogen or progesterone), given orally or via a patch.

• Osteoporosis (increased risk of bone fractures). Lowered testosterone levels lead to a loss of calcium, which may cause osteoporosis (thinning, brittle bones). Treatment with bisphosphonates can help reverse the effects of osteoporosis.

• Weight gain. Some prostate cancer treatments can cause fluid retention, weight gain and a loss of muscle mass. During treatment, men should stay as active as possible.

Side Effects of Radiation Therapy

Changes to the skin are the most common side effects of radiation therapy. The changes can include dryness, swelling, peeling, redness and blistering. It’s especially important to contact your health care team if there is any open skin or painful areas, as this could indicate an infection. Infections can be treated with an oral antibiotic or topical antibiotic cream.

Radiation can also cause mild urinary burning, burning in the rectum or a change in stool habits. Your health care team can recommend approaches to alleviate the discomfort of these side effects should they occur.

Side Effects of Chemotherapy

The side effects of chemotherapy depend on the type and dose of drugs given and the length of time they are used, and can include:

• Achiness
• Hair loss
• Increased risk of infection (from having too few white blood cells)
• Easy bruising or bleeding
• Changes in memory or thinking
• Peripheral neuropathy (numbness or tingling in hands and feet)

Some side effects may occur across treatment approaches. This section provides tips and guidance on how to manage these side effects should they occur.

Managing Digestive Tract Symptoms

Nausea and vomiting

• Avoid food with strong odors as well as overly sweet, greasy, fried or highly seasoned food.
• Eat meals cold or at room temperature, which often makes food more easily tolerated.
• Nibble on dry crackers or toast. These bland foods are easy on the stomach.
• Having something in your stomach when you take medication may help ease nausea.

Diarrhea

• Drink plenty of water. Ask your doctor about using drinks such as Gatorade that provide electrolytes. Electrolytes are body salts that must stay in balance for cells to work properly.
• Over-the-counter medicines such as loperamide (Imodium A-D and others) and prescription medications are available for diarrhea but should be used only if necessary. If the diarrhea is bad enough that you need medicine, contact a member of your health care team.
• The BRAT diet (bananas, rice, applesauce, toast) and soluble fiber such as oats, bran and barley can help with diarrhea. Foods high in insoluble fiber, such as leafy greens and most fruits should be avoided as they can worsen diarrhea. Oily foods should also be avoided.
• Avoid foods high in refined sugar and those sweetened with sugar alcohols such as sorbitol and mannitol.

Loss of appetite

• Eating small meals throughout the day is an easy way to take in more protein and calories, which will help maintain your weight. Try to include protein in every meal.
• To keep from feeling full early, avoid liquids with meals or take only small sips (unless you need liquids to help swallow). Drink most of your liquids between meals.
• Keep high-calorie, high-protein snacks on hand such as hard-boiled eggs, peanut butter, cheese, ice cream, granola bars, liquid nutritional supplements, puddings, nuts, canned tuna or trail mix.
• If you are struggling to maintain your appetite, talk to your health care team about whether appetite-building medication could be right for you.

Managing Fatigue

Fatigue (extreme tiredness not helped by sleep) is one of the most common side effects of many cancer treatments. If you are taking a medication, your doctor may lower the dose of the drug, as long as it does not make the treatment less effective. If you are experiencing fatigue, talk to your doctor about whether taking a smaller dose is right for you.

There are a number of other tips for reducing fatigue:

• Take several short naps or breaks during the day.
• Take walks or do some light exercise, if possible.
• Try easier or shorter versions of the activities you enjoy.
• Ask your family or friends to help you with tasks you find difficult or tiring.

There are also prescription medications that may help, such as modafinil. Your health care team can provide guidance on whether medication is the right approach for your individual circumstances.

Managing Pain

There are a number of options for pain relief, including prescription and over-the-counter medications. It’s important to talk to a member of your health care team before taking any over-the-counter medication to determine if it is safe and to make sure it will not interfere with your treatment. Many pain medications can lead to constipation, which may make your pain worse. Your doctor can prescribe medications that help to avoid constipation.

Physical therapy, acupuncture and massage may also be of help in managing your pain. Consult with a member of your health care team before beginning any of these activities.

Q: I was just diagnosed with prostate cancer. What questions should I ask the oncologist about the recommended treatment approach?

A: Here are some questions you should ask; others will likely arise in the course of your discussion.

• What are the goals of treatment?
• How long will treatment last?
• Do you have any written information about this treatment?
• What are the side effects of this treatment?
• Are there any ways to help manage side effects?
• How do I know if a side effect is severe enough to call you?
• Are there any other treatment options?
• Will treatment need to be given at a center that specializes in prostate cancer?
• Are there any clinical trials I should be aware of?
• What is the best way to let you know when I have questions about treatment?

Q: I’ve just been diagnosed with prostate cancer and have been told I am at low risk for developing an aggressive form of the disease. Are there any tests available to confirm that?

A: There are genetic tests available for this purpose; they include Oncotype DX, Decipher, Prolaris and ProMark. These tests can identify which men are truly at low-risk (and can be managed through active surveillance) and which men should seek immediate treatment. Your doctor can provide additional information should you wish to pursue this testing.

Q: My brother has prostate cancer. I want to help with caregiving, but I live far away. What can I do?

A: Even from a distance, you can provide ongoing emotional support to your brother and to his primary caregiver. It is sometimes easier for people to talk about difficult topics over the phone than in person, so be willing to have in-depth and serious conversations. You can also help coordinate medical appointments (and send reminders to your brother and his caregiver about those appointments), provide verbal updates to other family members, and share information on how your brother is feeling (if he agrees) in an on-line journal such as CaringBridge.