Prostate cancer happens when a tumor grows in the prostate gland, which makes the liquid portion of semen. Cancer that spreads outside the prostate gland to the lymph nodes, bones, or other areas is called metastatic prostate cancer. Currently, no treatments can cure advanced prostate cancer. But there are ways to help control its spread and related symptoms.
Treatments that slow the spread of advanced prostate cancer and ease the symptoms often cause Some patients — often those who are older —decide that the risk of side effects outweighs the benefits of treatment. These patients may choose not to treat their advanced prostate cancer.
It's important to remember that researchers are always searching for new and better treatments that will cause fewer side effects and offer better disease control and longer survival rates.
Hormone Therapy for Prostate Cancer
Male hormones, specifically testosterone, fuel the growth of prostate cancer. Lowering the amount and activity of testosterone can slow the growth of advanced prostate cancer. Hormone (endocrine) therapy, known as androgen ablation or androgen suppression therapy, is the main treatment for advanced prostate cancer.
In many patients, endocrine therapy offers temporary relief of symptoms of advanced prostate cancer. Endocrine therapy may reduce tumor size and levels of prostate-specific antigen (PSA) in most men. PSA is a substance made by the prostate gland that, when present in excess amounts, signals the presence of prostate cancer.
Hormone therapy is not without side effects. Some of the more serious side effects include loss of sex drive, impotence, weakened bones (osteoporosis), and heart problems.
Eventually, most patients with advanced prostate cancer stop responding to hormone therapy. Doctors call this castrate-resistant prostate cancer.
Endocrine Drugs for Prostate Cancer
Drugs work as well as prostate cancer surgery (orchiectomy — removal of the testicles) to reduce the level of hormones in the body. Most men opt for drug therapy rather than surgery. The three types of hormone-related drugs approved to treat advanced prostate cancer include luteinizing hormone-releasing hormone (LHRH) analogs, LHRH antagonists, and antiandrogens.
LHRH analogs
Most patients who receive hormonal therapy choose LHRH analogs. These drugs work by decreasing testosterone production to very low levels by depleting the pituitary gland of the hormone needed to produce testosterone. But before this drop in testosterone occurs, patients experience a brief and temporary increase in testosterone production and tumor growth. This is due to a temporary increase in the release of LHRH from the pituitary gland, which boosts testosterone production.
This phenomenon, called tumor flare, can cause increased symptoms from the prostate cancer that didn't exist before the patient received the therapy. Some doctors prescribe antiandrogens (described below) to fight the symptoms caused by tumor flare. LHRH analogs are given as a shot or placed as small implants under the skin.
The most commonly used LHRH analogs in the U.S. are goserelin (Zoladex), histrelin, leuprolide (Eligard, Lupron), and triptorelin (Trelstar). They cause side effects similar to those from the orchiectomy surgery. These drugs carry a risk of triggering diabetes, heart disease, osteoporosis, and/or stroke. Before starting one of these drugs, patients should tell their doctor if they have a history of diabetes, heart disease, stroke, heart attack, high blood pressure, high cholesterol, or cigarette smoking.
LHRH antagonists
These drugs have been approved for use as hormone therapy in patients with advanced prostate cancer. LHRH antagonists lower testosterone levels more quickly than LHRH analogs. Also, they don't cause a tumor flare (temporary rise in testosterone levels) as LHRH analogs do.
Degarelix (Firmagon) is an LHRH antagonist used to treat advanced prostate cancer. It has been shown to decrease the progression of disease, but further trials are needed to look at long-term outcomes. It is fairly well tolerated, with common side effects being local injection site problems and increased liver enzymes.
GnRH receptor antagonists
Relugolix (Orgovyx) is the first oral gonadotropin-releasing hormone (GnRH) receptor antagonist approved by the FDA for adult patients with advanced prostate cancer. A hormone therapy drug, it is taken once a day and works by binding to and blocking the GnRH receptor. This stops the pituitary gland from producing luteinizing hormone and follicle-stimulating hormone.
The most common side effects are muscle pain, hot flashes, diarrhea, and constipation.
Antiandrogens
These prostate cancer drugs work by blocking the effect of testosterone in the body. Antiandrogens are sometimes used along with orchiectomy or LHRH analogs. This is because the other forms of hormone therapy remove about 90% of the testosterone circulating in the body. Antiandrogens may help block the remaining 10% of circulating testosterone. Using antiandrogens with another form of hormone therapy is called combined androgen blockade (CAB), or total androgen ablation. Antiandrogens may also be used to fight the symptoms of tumor flare (a temporary rise in testosterone that occurs with the use of LHRH agonists). Some doctors prescribe antiandrogens alone rather than with orchiectomy or LHRH analogs.
Available antiandrogens include abiraterone acetate (Yonsa, Zytiga), apalutamide (Erleada), biclutamide (Casodex), darolutamide (Nubeqa), enzalutamide (Xtandi), flutamide (Eulexin), and nilutamide (Nilandron). Patients take antiandrogens as pills. Diarrhea is the primary side effect when antiandrogens are used as part of combination therapy. Less likely side effects include nausea, liver problems, and fatigue. When antiandrogens are used alone, they may cause a reduction in sex drive and impotence.
Combination Radiation and Endocrine Therapy
Sometimes, patients receive hormone therapy along with external beam radiation therapy for the treatment of prostate cancer. This treatment uses a high-energy X-ray machine to direct radiation to the prostate tumor. For patients with intermediate or high-risk prostate cancer, studies show this combination is more effective at slowing the disease than endocrine therapy or radiation therapy alone.
Radiation can also come in the form of radiopharmaceutical drugs, which are aimed at helping control and slow the spread of the cancer. They are used to treat patients who have received therapy designed to lower testosterone. Radium-223 (Xofigo) is an intravenous drug approved for use in men who have advanced prostate cancer that has spread only to the bones. The drug works by binding to minerals within bones to deliver radiation directly to bone tumors.
Two other similar drugs are samarium-153 (Quadramet) and strontium-89 (Metastron).
Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) is also taken intravenously. It specifically targets a molecule on the surface of prostate cancer cells called PSMA.
Secondary Endocrine Therapy
At some point, PSA levels begin to rise despite treatment with hormone therapy. This signals that hormone therapy is no longer working to reduce testosterone levels in the body. When this happens, doctors may decide to make changes to the hormone therapy. This is called secondary hormone therapy. It can be done in several ways.
For instance, if you have had surgery to remove your testicles, your doctor may suggest that you begin taking an antiandrogen. If you have been using combination therapy that involves an antiandrogen and LHRH analogs, your doctor may stop the use of the antiandrogen. This is known as antiandrogen withdrawal.
Another option is to change the type of hormone drug. But the use of an LHRH drug must be continued to prevent a testosterone rebound from stimulating the growth of prostate cancer cells.
When used at high doses, ketoconazole (an antifungal agent) slows the production of testosterone in the adrenal glands and testes. Response rates in a second-line setting are 20%-40% with major side effects. Doses range from 200 milligrams three times a day to 400 milligrams three times a day. The drug must be given with hydrocortisone to prevent adrenal insufficiency.
Standards of Care in Hormone Therapy
Most doctors agree that hormone therapy is the most effective treatment available for patients with advanced prostate cancer. But they disagree on exactly how and when hormone therapy should be used. Here are a few issues regarding standards of care:
Timing of cancer treatment
The disagreement is due to opposing beliefs. One is that hormone therapy should begin only after symptoms from the metastases, such as bone pain, show up. The counter belief is that hormone therapy should start before symptoms occur. Earlier treatment of prostate cancer is linked to a lower rate of spinal cord compression, obstructive urinary problems, and skeletal fractures. But it doesn't affect how long patients live; survival is the same whether treatment starts early or is delayed.
The only exception to the above is for patients with lymph node-positive cancer who had their prostates removed. In these patients, starting hormone therapy androgen deprivation as an adjuvant immediately after surgery (prostatectomy) resulted in a huge improvement in progression-free survival, prostate cancer-specific survival, and overall survival.
Length of cancer treatment
The disagreement in this situation is between continuous androgen deprivation (hormone therapy) and intermittent androgen deprivation.
In early 2012, it was discovered that intermittent androgen deprivation is equal in long-term survival to continuous androgen deprivation. A new treatment approach, in which androgen deprivation was given for eight to nine months and then discontinued if the PSA normalized, was published. Re-treatment is recommended only when the PSA level becomes greater than 10, with tracking every two months.
Combination vs. single-drug therapy
There is also a debate about whether using a combination of hormone therapies or just a single antiandrogen drug works best to treat prostate cancer. The studies are unclear. But patients who receive combination therapy are more likely to experience treatment-related side effects than patients receiving a single form of hormone therapy.
Chemotherapy for Prostate Cancer
Patients who no longer respond to hormone therapy have other options.
Docetaxel (Taxotere)
The chemotherapy drug docetaxel (Taxotere) taken with or without prednisone (a steroid) is the standard chemotherapy treatment plan for patients who no longer respond to hormone therapy. Docetaxel works by preventing cancer cells from dividing and growing. Patients receive docetaxel, along with prednisone, through a shot. Side effects of docetaxel are similar to most chemotherapy drugs and include nausea, hair loss, and bone marrow suppression (the decline or halt of blood cell formation). Patients may also experience neuropathy (nerve damage causing tingling, numbness, or pain in the fingers or toes) and fluid retention.
Docetaxel, when used with or without prednisone, was the first chemotherapy drug proven to help patients live longer with advanced prostate cancer. The average survival was improved by about 2.5 months when compared to mitoxantrone with or without prednisone. Docetaxel has the best results when given every three weeks as compared to weekly dosing.
Cabazitaxel (Jevtana)
Cabazitaxel (Jevtana) is another chemotherapy drug, used in combination with the steroid prednisone, to treat men with prostate cancer. Cabazitaxel (Jevtana) is used in men with advanced prostate cancer that has progressed during or after treatment with docetaxel (Taxotere).
The safety of cabazitaxel (Jevtana) and its effectiveness were established in a single, 755-patient study. All study participants had previously received docetaxel (Taxotere). The study was designed to measure overall survival (the length of time before death) in men who received cabazitaxel (Jevtana) in combination with prednisone as compared to those who received the chemotherapy drug mitoxantrone in combination with prednisone. The median overall survival for patients receiving the cabazitaxel (Jevtana) was 15.1 months compared with 12.7 months for those who received the mitoxantrone treatment plan.
Side effects in those treated with cabazitaxel (Jevtana) included significant decrease in infection-fighting white blood cells (neutropenia), anemia, low level of platelets in the blood (thrombocytopenia), diarrhea, fatigue, nausea, vomiting, constipation, weakness, and renal failure.
Provenge for Advanced Prostate Cancer
Sipuleucel-T (Provenge) is a "vaccine" for advanced prostate cancer that helps prolong survival.
Provenge isn't your everyday vaccine. It's an immune therapy created by harvesting immune cells from a patient, genetically engineering them to fight prostate cancer, and then infusing them back into the patient.
It's approved only for the treatment of patients with few or no prostate cancer symptoms , whose cancer has spread outside the prostate gland and is no longer responding to hormone therapy.
Once a cancer grows beyond a certain point, the immune system has a hard time fighting it. One reason is that the cancer cells look a lot like normal cells to the immune system. Another reason is that tumors may give off signals that manipulate the immune system into leaving them alone.
Provenge bypasses these problems. The treatment first removes a quantity of dendritic cells from a patient's blood. Dendritic cells show pieces of tumor to immune cells, priming them to attack cells that carry those pieces.
The patient's doctor ships the cells to Provenge's maker Dendreon, where they expose these cells to Provenge. Provenge is a molecule made inside genetically engineered insect cells.
Once these cells have been exposed to Provenge, they're shipped back to the doctor who infuses them back into the patient. This is done three times in one month. The first infusion primes the immune system. The second and third doses lead to an anticancer immune response.
The most common side effect is chills, which occurs in more than half of the men who receive Provenge. Other common side effects include fatigue, fever, back pain, and nausea. Provenge has been remarkably safe. But clinical trials suggest that the treatment might be linked to a slightly higher risk of stroke.
Surgery for Prostate Cancer
Salvage prostatectomy
In some cases of advanced or recurrent prostate cancer, surgeons may remove the entire prostate gland in a surgery known as "salvage" prostatectomy. They usually do not perform the nerve-sparing form of prostatectomy. Often, surgeons will remove the pelvic lymph nodes at the same time.
Cyrosurgery
Cyrosurgery (also called cryotherapy) may be used in cases of recurrent prostate cancer, if the cancer has not spread beyond the prostate. Cryosurgery is the use of extreme cold to destroy cancer cells.
Orchiectomy
To lower testosterone levels in the body, doctors may sometimes recommend removing the testicles, a surgery called orchiectomy. After this surgery, some men choose to get prosthetics (artificial body parts) that resemble the shape of testicles.
TURP/TUIP
Doctors may also remove part of the prostate gland with one of two procedures, either a transurethral resection of the prostate (TURP) or a transurethral incision of the prostate (TUIP). This relieves blockage caused by the prostate tumor so that urine can flow normally. This is a palliative measure, which means it is done to increase the patient's comfort level, not to treat the prostate cancer itself.
Emerging Therapies for Prostate Cancer
Researchers are pursuing several new ways to treat advanced prostate cancer. Vaccines that alter the body's immune system and use genetically modified viruses show the most promise.
Immune or genetic therapies have the potential to deliver more targeted, less invasive treatments for advanced prostate cancer. This would result in fewer side effects and better control of the prostate cancer.
Palliative Care for Advanced Prostate Cancer
Palliative care is a type of treatment that helps you deal with cancer symptoms and side effects. With advanced prostate cancer, this means things such as pain, tiredness, urinary problems, and stress. You can get palliative care at any stage of cancer and at any time during treatment.
Pain management
Let your care team know if you're in pain. They can offer medications and ways to manage pain, including:
- Pain relievers ranging from over-the-counter acetaminophen and NSAIDs to opioids
- Antidepressants or anti-seizure medicines to help with nerve pain
- Steroids
- Bone treatments, including targeted radiation and medications to help prevent fractures, such as denosumab or zoledronic acid
- Nerve blocks or electronic nerve stimulation
- Hot or cold packs
- Relaxation techniques, including meditation, yoga, and massage
- Complementary treatments such as acupuncture and hypnosis
Fighting fatigue
Some treatments for advanced prostate cancer can make you extremely tired, and so can stress and dealing with pain. You can help increase your energy level by eating nutritious food and getting mild exercise (with your doctor's OK). Pace yourself during the day and rest when you need to, but limit napping — it can make it harder to sleep well at night.
Bladder problems
If you have trouble either emptying your bladder or holding your pee, physical therapy and bladder training (peeing on a schedule) can help. You may get trained to use a catheter to drain your bladder or collect urine.
Emotional support
Caring for your mental health can help you manage advanced prostate cancer symptoms, including pain and fatigue. This can include:
- Psychotherapy
- Medication, such as antidepressants or antianxiety drugs
- Relaxation techniques
- Meditation and mindfulness
- Journaling
- Sharing your feelings with family and friends
It may help to join a support group to connect with others dealing with prostate cancer. Ask your care team if there's an in-person group in your area or look online for a virtual option.
FAQs on Treatment for Advanced Prostate Cancer
What are the final stages of prostate cancer?
The most advanced stage of prostate cancer is stage IV, also called metastatic prostate cancer. At this stage, the cancer has spread to other parts of your body beyond your prostate, such as lymph nodes, bones, or other organs.
How long does one get to live with advanced prostate cancer?
Everyone responds to treatment differently, so it's impossible to say how long any particular person will live with advanced prostate cancer. But statistics show that someone diagnosed with metastatic prostate cancer is 37% as likely as someone without the disease to be alive in five years.
Is it possible to cure advanced prostate cancer?
Advanced prostate cancer is not considered curable. Treatment can help you live longer and ease your symptoms.
