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Treatment Options

There are many treatment options available for prostate cancer based on the stage of the disease progression. Work together with your doctor to weigh the risks, advantages, and disadvantages of each option and its side effects to determine what treatment is right for you or your loved one.

Read the NCCN Guidelines for Prostate Cancer Patients from the National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 21 of the world’s leading cancer centers. Developed by hundreds of medical experts to provide step-by-step strategies that many doctors follow, the NCCN Guidelines are the most comprehensive and most frequently updated clinical practice guidelines available for any area of medicine.

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Localized Prostate Cancer

Prostate cancer is called localized or early stage disease when no cancer cells have spread outside of the prostate gland. The goal of all options is to remove or destroy cancer cells before they can spread to other tissues in the body or at least prevent a man from suffering any harm. Selecting the right treatment is difficult because there are so many options available and the proper studies have never been done to determine if one is better than the other. Therefore, each man must take part in deciding which treatment to receive. All the treatments have advantages and disadvantages and it helps if patients ask the right questions so they can participate in shared decision making with their healthcare team and make the best choice. The most important questions to ask are:

  • What are the odds or chances that the treatment will cure me of my disease?
  • What are the odds or chances that I will develop any of the possible side effects or complications?

These questions are important because not all doctors get the same results. More experienced doctors tend to have better outcomes. The following is a list of all the options for treating localized disease.

 

Watchful Waiting

Watchful waiting describes the least invasive option in which the patient does not receive treatment unless symptoms develop or the prostate cancer spreads to other parts of the body. It has the advantage of being able to avoid the harmful side effects that can occur with any of the definitive treatment options, however, a patient selecting this option may miss out on a chance to be entirely cured of their disease and then develops symptoms and complications if the cancer spreads. It is most appropriate in less healthy men or those with a short life expectancy. They see the doctor for periodic exams and to have their PSA monitored and this continues unless symptoms of the cancer occur.

Active Surveillance

Active surveillance involves closely monitoring prostate cancer with routine digital rectal exams (DREs) and prostate specific antigen (PSA) tests - usually every 3-6 months. Periodic biopsies have been recommended although the frequency has been declining and is being replaced by multi-parametric MRI. Active treatment, such as surgery or radiation therapy, is not recommended unless there is evidence that the size of the cancer or the tumor grade is increasing. This treatment is most appropriate for men with very low- or low-risk prostate cancer, meaning a T1C or T2a cancer, A PSA less than 10 ng/ml and Gleason 3+3 disease because most of them will never cause a man any harm. Some men with Gleason 3+4 cancer may also be reasonable candidates for this option after also considering age and family history. The benefit of this treatment is that the majority of men with low risk disease may be able to avoid treatment entirely and its possible side effects. The risk is that by delaying treatment, the cancer may be more difficult to cure. So far this risk is very low in properly selected patients, meaning that only a few men out of 100 will be worse off because they delayed treatment. Genomic testing may help with selecting lower risk cancers.

Radical Prostatectomy

The surgical treatment for localized prostate cancer is a radical prostatectomy, an operation that removes the entire prostate along with both seminal vesicles and a portion of both vas deferens. This treatment can cure the cancer providing no cells have spread outside the prostate gland. Unless contraindicated, doctors can preserve the two nerves responsible for erections, called a nerve-sparing radical prostatectomy. The success depends on several factors including the age and health of the patient and the expertise of the surgeon. Some studies suggest that better results occur with doctors performing more than 20-30 of these operations per year, so men should specifically ask how many their doctor performs. Also, the frequency of side effects varies from doctor to doctor so men considering this option should ask their surgeon about their specific experience. There are several ways a radical prostatectomy can be performed as described below. With each of them, a catheter is left in the bladder through the urethra for 1-2 weeks. Urinary control and sexual function usually take weeks to months to improve. A PSA is measured at one month and then usually every three months for two years. It should become undetectable by one month after surgery.

Side Effects of Surgery

  • Impotence (loss of ability to have erections)
  • Urinary incontinence
  • Urethral stricture (narrowing of the urinary channel)
  • Shortening of penis
  • Infection
  • Lymphocele (collection of lymph fluid near prostate bed)
  • Death (rare)

Radical Retropubic Prostatectomy (RRP)

The operation is performed under a general or spinal anesthetic. An incision is made from just below the navel to the pelvic bone without damaging muscles. This enables the surgeon the ability to feel the prostate, the surrounding tissues, and the pelvic lymph nodes. The decision to spare the nerves for erections depends on the biopsy results and the digital exam. There is no completely accurate way to confirm whether or not cancer is present in a pelvic nerve unless the nerve is removed and analyzed by a pathologist while the patient is under anesthesia. After the prostate is removed, the urethra must be sewn back to the bladder. A catheter is left in the bladder through the penis for one two weeks to allow healing to occur. Men are hospitalized for 1-3 nights. Most activities can be resumed in about 4 weeks.

Radical Perineal Prostatectomy (RPP)

The operation is usually performed under general anesthesia. An incision is made between the scrotum and the anus. Generally men lose less blood with this operation compared to the retropubic method outlined above, the surgeon still has the ability to feel along the pelvic nerves to determine whether they can be saved or must be removed. Recovery is generally faster compared to the RRP.

Laparoscopic Radical Prostatectomy (LRP)

Also referred to as "minimally invasive" or "keyhole surgery", the operation begins by inserting a needle into the abdomen to inflate it with carbon dioxide thereby separating the abdominal wall from the internal organs and providing the space necessary to perform the surgery. Three or four small incisions are made in the lower abdomen through which surgical instruments and a telescopic lens are placed. The doctor views the operative field on a video monitor. After the prostate has been cut away from the bladder and the urethra, it’s removed from the body through a small incision made above the pubic bone. Less blood loss occurs with this approach compared to the retropubic approach.

Robot-Assisted Laparoscopic Radical Prostatectomy (RALP)

As with the laparoscopic procedure described above, this operation also begins by inserting a needle into the abdomen to inflate it with carbon dioxide thereby separating the abdominal wall from the organs and providing the space necessary to perform the surgery. Three or four small incisions are made in the lower abdomen as access for surgical instruments and a telescopic lens that are attached to robotic arms. They are connected through special cables to instruments providing the surgeon with robotic control of the procedure and a three-dimensional view of the inside of the abdomen shown on a video monitor. The doctor performs the operation sitting at a console near the operative table. Movements made at the console control the robotic arms attached to the patient. After the prostate has been cut away from the bladder and the urethra, it's removed from the body through an incision above the pubic bone. This method also has less blood loss than the RRP.

Advantages of Prostatectomy

  • One-time procedure
  • May prevent spread of cancer to other tissues
  • May cure early-stage prostate cancer (if cancer cells are only located in the prostate)
  • Removes the prostate gland and the problem of future overgrowth of the prostate (called BPH—benign prostate hyperplasia—the non-malignant enlargement of the prostate)
  • May help extend life
  • When this operation is performed by an expert, the advantages are much more likely to occur, and the disadvantages are less likely to occur

Disadvantages of Prostatectomy

  • Requires hospitalization
  • May cause side effects including:
    • Impotence (also known as erectile dysfunction or ED, the inability to get an erection of sufficient quality for sexual intercourse)
    • Incontinence (loss of urinary control)
    • Urethral stricture making urination difficult
    • Shortening of the penis due to reconnecting bladder to urethra
  • The operation carries a small risk of mortality

External Beam Radiation

External beam radiation is a treatment for prostate cancer that uses a machine to deliver rays of high energy. It works on the DNA, which is contained in all living cells. DNA controls the ability of cells to divide. Cancer cells harm us because they continue to divide without stopping. The energy from radiation machines is so strong that it can damage the DNA in cancer cells, causing them to die or making them unable to divide. Cancers are treated with alpha, beta, proton and neutron particles; and gamma and x-ray waves. Prostate cancer is most commonly treated using gamma rays. This treatment is appropriate for men with any Gleason score, however, for tumors with a Gleason score of 7-10, the radiation should be combined with drugs that lower the male sex hormone, testosterone, which fuels the growth of prostate cancer. The appropriate duration of this treatment varies depending on the tumor grade. Combining androgen deprivation therapy with the radiation for these men significantly improves survival. External radiation can be delivered in a variety of ways but similar to the various surgical methods, no good studies have proven whether one approach is better than the other in terms of cancer control or side effects. Studies are in progress to determine if giving higher doses at each treatment over a shorter time period can result in the same outcomes as longer treatments. Similar to surgery, physician experience is important so men should specifically ask their radiation therapist the same questions as for the surgeon. A recent development has been the development of a spacer (SpaceOAR) that is placed through the perineum into the space between the rectum and prostate to temporarily separate the two organs. Studies have shown it can reduce some of the bowel side effects.

  • External Beam Radiation Therapy (EBRT): radiation is generated and administered by a machine outside the body, usually in brief daily sessions for several weeks. You can read or join discussions about EBRT at the EBRT bulletin board
  • Intensity-Modulated Radiation Therapy (IMRT) minimizes radiation damage to normal tissues by using a large number of narrow beams rather than a single, wide beam thereby allowing for greater control of the dose of radiation.
  • 3-Dimensional Conformal Radiation Therapy (3DCRT) treatment allows closer targeting of the prostate gland. Uncontrolled studies suggest better outcomes with IMRT compared to 3dCRT; however, definitive proof is lacking at this time.
  • CyberKnife Robotic System is a non-invasive treatment option for prostate cancer that has the ability to deliver targeted and destructive doses of radiation from almost any angle to the body. It tracks tumor motion and automatically corrects the aim of the treatment beam when movement is detected. Studies have not determined if it offers clear clinical advantages. Read additional information at: http://www.cyberknife.com/
  • The Calypso Tracking System (GPS for the body) was designed to improve IMRT radiation by adjusting for any movement of the prostate by placing tiny sensors in the gland before the treatment begins to emit radiofrequency waves that allow for the very accurate alignment of a man’s prostate before each treatment session. It can also be used to monitor the position of the prostate at all times during radiation treatment delivery, objectively pinpointing the location of tumors and helping to minimize the amount of healthy tissue surrounding the prostate or prostate tumor that might be radiated due to organ movement.
  • Proton Beam Therapy (PBT) uses proton beams instead of x-rays to kill cancer. Proponents believe it offers an ability to deliver more precise radiation; however, so far no well-done study has demonstrated any clinical advantage over IMRT. In addition, it is far more costly. Recently, the American Society of Therapeutic Radiation (ASTRO) issued the following policy statement: While proton beam therapy is not a new technology, its use in the treatment of prostate cancer is evolving. ASTRO strongly supports allowing for coverage with evidence development for patients treated on clinical trials or within prospective registries. ASTRO believes that collecting data in these settings is essential to informing consensus on the role of proton therapy for prostate cancer. Learn more about PBT by visiting The National Association of Proton Therapy website.

Advantages of External Radiation Therapy

  • Avoids major surgery
  • May cure prostate cancer in its early stages and may help extend life or eliminate symptoms in later stages
  • Many of the side effects improve over time.

Disadvantages of Radiation Therapy

  • May cause damage to healthy cells, leading to the following possible side effects:
    • Tiredness
    • Skin reactions
    • Frequent and painful urination
    • Upset stomach
    • Diarrhea
    • Rectal irritation or bleeding
    • Urinary incontinence
    • Erectile dysfunction
    • Small increased risk of bladder and colon cancer
    • If cancer is not cured, surgery can be performed but the complication rate is much higher
    • PSA level may take 1-2 years to reach its lowest level

Brachytherapy

Another way to deliver radiation is by placing tiny radioactive seeds or radioactive wires directly into the prostate gland. In Latin, 'brachy' means short distance, so this treatment involves placing the radiation close to the cancer. It can be done either by leaving radioactive seeds about the size of a grain of rice in the prostate permanently or by placing radioactive wires into the gland for a short time and then removing them. The best candidates are those men with low or intermediate risk disease. The results are less clear for men with a Gleason score of 8-10. Men must have a prostate gland that is less than 40-50 grams in size. However, men with a larger gland may still be candidates if the gland shrinks after several months of hormone therapy. Men with significant urinary difficulties also may not be good candidates, but they can be given drugs to improve those symptoms and then may still be a reasonable candidate. In the higher risk men, androgen deprivation therapy can be combined with the seeds, but the effect on survival has not been well studied.

Permanent Brachytherapy or Seed Implantation

This treatment is also called LDR or low dose rate brachytherapy because of a low intensity of the seeds being used. Three types of radioactive seeds are available for this treatment, Iodine-125, Palladium-103 or Cesium-131. They differ in the intensity of the radiation being delivered and the time until the radiation decays or disappears. About 97% of the radiation is gone in by 300 days for the iodine seeds, 85 days for the palladium seeds and 49 days for the cesium seeds. No study has demonstrated whether one is better than the other but the iodine may have fewer side effects and is used most often. Prior to the procedure men come in to have an ultrasound to accurately determine the size of the prostate and the number of seeds that will be used. On the day of the implant, the patient is given an enema and an antibiotic. He is then given a general or spinal anesthetic and an ultrasound probe is placed into the rectum to visualize the prostate. A needle guide is attached to the probe, which helps directs the needles containing the seeds into specific locations in the prostate. The number of seeds used depends on the size of the gland. After the procedure, a catheter is left in place until the anesthesia wears off and is then removed. Patients go home the same day when they are able to urinate and can tolerate oral intake. Full activity can be resumed within a few days. A follow-up exam and PSA is measured at one month and every 3 months for two years. In some cases the PSA may rise for a short time in the first two years but it does not mean the cancer has returned and it then goes back down. Side effects usually improve over time.

Advantages of Permanent Brachytherapy

  • Can avoid surgery
  • Treatment completed in one day
  • May cause fewer side effects than external beam radiation
  • Surgery still possible if cancer not eliminated but complication rate is higher

Disadvantages of Permanent Brachytherapy

  • Impotence
  • Incontinence
  • Urinary obstruction
  • Rectal Injury
  • Urethral stricture
  • Blood in Urine
  • Urinary infection

Temporary Brachytherapy

Another name for this treatment is High Dose Rate Brachytherapy (HDR) because it gives off much more radiation each day than the permanent seed implants. The best candidates for HDR are the same as for external radiation, however, in the higher risk patients, HDR is being combined with external radiation and androgen deprivation therapy. The long- term impact on survival for this aggressive treatment is unclear and studies have not yet been done to know how it compares with the other treatment options. The procedure requires hospitalization usually for 1-2 nights and limited motion to avoid moving the implant. It usually is performed under general anesthesia. An enema and antibiotic are given prior to the procedure and then anesthesia is administered. An ultrasound probe is placed in the rectum to guide the placement of the thin plastic tubes through the perineum into the prostate. These tubes are held in place with sutures. The patient is woken and then transferred to radiology where a CAT scan is performed to determine the amount of radiation needed. The next stop is the radiation center where a computer-controlled machine pushes radioactive wires of Iridium-192 into the plastic tubes. They are left in place for a specified time and then removed. The patient is sent to their hospital room and returns the next day for reinsertion of the radioactive needles. In some cases the procedure is repeated 1-2 weeks later. Men return in a few weeks and then every three months for a follow-up exam and PSA level. It can take 1-2 years before the PSA drops to its lowest level. Learn more about brachytherapy by visiting the seed pods website.

Advantages of HDR

  • Avoids surgery
  • Completed in less time than external beam radiation
  • No radioactive seeds left in the body

Disadvantages of HDR

  • Requires hospitalization and anesthesia
  • More inconvenient than permanent brachytherapy
  • Not widely available
  • May not eliminate cancer
  • Long-term impact on survival not known
  • Side effects include:
    • Urinary retention
    • Bowel Injury
    • Impotence
    • Burning on urination
    • Urinary incontinence
    • Weak urinary stream
    • Blood in urine

Cryotherapy

Cryotherapy is a procedure that uses very cold temperatures to kill prostate cancer cells. Although it has been used to treat prostate cancer for over 20 years, it has not been well studied in controlled trials therefore it is not exactly known how well it compares to radiation and surgery. Cryotherapy is used to treat early stage, localized prostate cancer (stages T1 and T2), or cancer that recurs following radiation therapy. It is not ideal for men with “normal” sexual function because of the higher risk of impotence. Also, it is not appropriate for men who have previously had surgery for rectal or anal cancer. Another limitation is in men with a large prostate, although hormone therapy (see below) can be given for several months to shrink the size enough to make it possible to perform this procedure.

About the Procedure

This outpatient procedure is completed in several hours, under spinal, epidural, or general anesthesia, after which the patient is usually able to go home. The patient must fast (no food or drink) for at least eight hours prior to the procedure. An enema is used to empty the colon and men receive an antibiotic to prevent infection. It starts by a catheter being inserted into the bladder through the urethra to circulate a warming solution, which prevents freezing of the urethra. An ultrasound probe is inserted into the rectum and the cryotherapy needles are inserted into the prostate through the perineum between the anus and the scrotum. Argon gas is passed through the needles into the prostate to freeze the gland for a few minutes and then Helium is passed through the same needles to thaw the frozen areas. The freeze-thaw usually is performed twice on each patient during the same anesthesia. A catheter may be left in the bladder after the procedure has been completed. An appointment will need to be made with the doctor to remove the catheter. Antibiotics may be prescribed to prevent infection. Regular checkups, imaging scans, and lab testing will be needed to monitor the response to treatment. The PSA can take several months to reach its lowest level.

Advantages of Cryotherapy

  • Less likely to cause bowel difficulties than radiation
  • Procedure takes a few hours
  • Patients may regain most activities within a few days
  • Less invasive than surgery
  • Less blood loss than surgery
  • Lower cost than surgery
  • Less pain than surgery
  • Can be repeated if necessary
  • An option for treating cancers that are considered inoperable

Disadvantages of Cryotherapy

  • Risk of erectile dysfunction is high
  • Long-term effectiveness compared to surgery and radiation is unclear
  • Blood in urine for a day or two after procedure
  • Soreness and Swelling of penis and scrotum
  • Burning sensations or pain in bladder and rectum
  • More frequent need to empty bladder and bowels (normal function is generally recovered over time)
  • Difficult or painful urination
  • Bleeding or infection in treated area
  • Urinary retention requiring a catheter for 1-2 weeks
  • Surgery more difficult if cancer not cured
  • Urinary incontinence
  • Injury to rectum resulting in rectal fistula (connection between the bladder and rectum), which may require surgery
  • Urethral stricture

For Other Reading

High-Intensity Focused Ultrasound (HIFU)

High-Intensity Focused Ultrasound (HIFU) is a minimally invasive treatment that uses high frequency ultrasound waves to produce very high temperatures to destroy targeted cancer cells. HIFU uses ultrasound to target the prostate, usually treating the entire gland.

The procedure has been used in Europe for over 10 years, but until recently, it was not available in the U.S. In 2015, the FDA gave approval to "ablate prostate tissue", which means it can be used in men with prostate cancer. The problem is that long-term survival data are not available and there are no good studies proving it is as effective as surgery or radiation. Most insurance companies and Medicare do not cover this procedure for prostate cancer.

Ideal candidates for HIFU are those who have low risk disease (Gleason 6, T1 or T2 disease and PSA under 10 ng/ml). Studies in progress to do focal treatment of a portion of the prostate rather than the entire gland to reduce side effects but long term impact will not be available for many years.

About the Procedure

The HIFU procedure is generally performed in a single session on an outpatient basis, requiring no hospital stay. It typically takes between 1-3 hours. Treatment is usually performed under general anesthesia but spinal anesthesia is sometimes possible. An enema is given prior to the procedure and an antibiotic is given to prevent infection. A catheter is placed in the bladder through the penis. Many men receive a TURP or transurethral resection of the prostate at the time of the HIFU to reduce the chance of developing urinary retention from swelling in the prostate. The ultrasound probe is inserted through the rectum that will show the prostate and deliver the focused ultrasound waves, which produce intense heat that can kill the cancer cells. The area destroyed by each wave is very small and precise. By repeating the process and moving the focal point, it is possible to destroy the cancerous tissue in the prostate. Patients are sent home the same day. The PSA declines over the next several weeks.

Advantages of HIFU

  • The procedure is minimally invasive enabling men to avoid surgery and radiation
  • Treatment can be repeated if necessary
  • Other therapeutic alternatives can be considered in case of incomplete results
  • HIFU can be used for the treatment of local recurrences (i.e. after external beam radiotherapy)
  • Studies underway to do focal treatment instead of treating entire gland

Disadvantages of HIFU

  • May not kill all cancer cells
  • Long-term impact on survival not known
  • Impotence
  • Incontinence
  • Urethral stricture
  • Urinary infection
  • Urinary retention
  • Rarely covered by insurance
  • Androgen deprivation therapy may be necessary for a large gland
  • Long-term impact on survival not known
  • Changes in ejaculation
  • If cancer not cured, surgery still possible but it has higher complication rates

If you are interested in HIFU, please talk to your doctor.

Approval and Reimbursement

The cost of HIFU ranges from $15,000 to $25,000. Medicare may pay for a portion of the expenses, but does not cover all expenses and private companies vary in their policy. Anyone considering this treatment should investigate the amount they may have to pay out of pocket.

Hormone Therapy

Prostate cancer cells require male hormones (testosterone and dihydrotestosterone) to grow. Hormone therapy, also called Androgen Deprivation Therapy or ADT decreases the production of testosterone by the testicles so that cancer cell growth slows down. This treatment can be delivered either by removing both testicles (bilateral orchiectomy), by using drugs that reduce the ability of the body to produce these hormones or by blocking the action of these hormones. Although it rarely eliminates all prostate cancer cells in the body, it does kill many of them and slows the growth of others. Hormone therapy is primarily used in men with advanced disease, but it is also used in men who are not good candidates for the other local therapies. It may be recommended for several months in some men treated with radiation therapy or to shrink the size of the prostate in men with a large gland prior to brachytherapy (seed implantation), cryosurgery or HIFU. In some cases men receive the treatment for several months and then it is discontinued and then restarted if and when the cancer begins to grow again. This is called Intermittent Androgen Therapy of IAD. It has the advantage of allowing side effects to disappear for several months so men do not have them constantly. However, in some cases the testosterone level never returns to normal so side effects persist.

Side effects of ADT

  • Hot flashes
  • Reduced libido
  • Osteoporosis (bone weakening) –  See more on bone health issues here.
  • Loss of muscle mass and increase of body fat
  • Impotence
  • Anemia (decreased level of red blood cells)
  • Depression
  • Gynecomastia (breast enlargement)
  • Increase in Cholesterol, triglycerides and Diabetes
  • Weight Gain
  • Cognitive Dysfunction

Types of Hormone (Androgen Deprivation) Therapies

Bilateral orchiectomy is an operation that removes both testicles, which produce 95% of the body's testosterone. The operation is performed as an outpatient under local, general, or spinal anesthesia. A small incision is made in the scrotum to remove both testicles, which is closed with self-absorbing sutures. The operation takes about 1 hour and men go home the same day. Ice is applied to the scrotum to reduce swelling. Most activities can be resumed within a few days.

Advantages of Orchiectomy

  • One-time procedure
  • Effective, permanent reduction in testosterone
  • Patients typically go home the same day as the surgery
  • Cost (relatively inexpensive) and convenience

Disadvantages of Orchiectomy

  • Reduced libido or sex drive
  • Impotence
  • Hot flashes
  • Procedure is irreversible possibly affecting men psychologically with absent testicles.
  • Hospitalization may be required if complications occur.
  • Will not allow for intermittent androgen deprivation (IAD) therapy

LHRH (Luteinizing Hormone Releasing Hormone) Agonists and Antagonists

LHRH is a hormone normally produced in the hypothalamus of the brain. Its role is to tell the pituitary gland to release LH or luteinizing hormone, which stimulates the testicles to produce testosterone. LHRH agonists and antagonists are drugs that stop the body from producing LHRH, which leads to a drop in the level of testosterone in the body. The difference between these two is that the agonists initially cause a short-term rise in the testosterone level in the body and after a few weeks it drops very low. In contrast, the antagonist drops the testosterone immediately, without causing any rise. Doctors are not sure whether one is better than the other therefore both are reasonable choices when ADT is the treatment of choice and men wish to avoid removing the testicles.

Currently available LHRH agonists:

  • Lupron® (leuprolide acetate)
  • Eligard® (leuprolide acetate)
  • Viadur® (leuprolide acetate implant)
  • Vantas® (histrelin implant)
  • Zoladex® (goserelin acetate)
  • Trelstar™ (triptorelin)

Advantages of LHRH Agonists

  • Easy administration of injections monthly or every 1, 3, 4, 6 or 12 months
  • In most cases, treatment with LHRH agonists is as effective as orchiectomy in reducing testosterone to castrate level
  • Side effects may be reversible upon termination of the treatment.

Disadvantages of LHRH Agonists

  • Side effects of hormone therapy may be difficult to treat and hard for some people to accept
  • Testosterone level rises during first two weeks of initiating therapy (flare response), which may cause increase in cancer symptoms in some men
  • Requires injections every 1, 3, 4, 6, or 12 months
  • May cause discomfort after injection
  • The drug may stop controlling the testosterone level in some cases
  • In some cases, another drug called an anti-androgen must be given to stop the cancer from worsening during the first two weeks of the first injection.

Currently Available LHRH Antagonists:

  • Degarelix (Firmagon)

Advantages of LHRH Antagonist

  • Reduces testosterone levels quickly without the initial "testosterone surge" seen with an LHRH agonist
  • Anti-androgen therapy is not needed to prevent possible flare symptoms
  • Side effects may be reversible when the drug is stopped.

Disadvantages of LHRH Antagonist

  • Overall side effects are the same as for the LHRH agonists
  • Discomfort at injection site
  • Treatment must be given monthly

Advanced Prostate Cancer

Prostate cancer is advanced when cancer cells have spread outside the prostate gland, either locally to the seminal vesicles, the bladder or nearby lymph nodes or to other parts of the body such as the lungs, the brain, the liver or the bones. This can occur either when the cancer is first diagnosed or later after a man has been given his initial treatment. When cancer has spread beyond the prostate, complete removal of the prostate or destruction of cancer tissue by radiation or cryosurgery is uncommon because no studies have demonstrated that it will improve survival. Treatment primarily is directed at lowering the male sex hormone, testosterone, because it stimulates the growth of these cancer cells wherever they are in the body. This treatment is called hormone therapy, androgen deprivation therapy or ADT or castration. For men with locally advanced stage T3 and T4 prostate cancer, studies show that combining ADT with radiation can improve survival. Treatments are also available that block the ability of testosterone to stimulate cancer cells. Other treatments are available to treat metastatic disease. Over the last several years, new treatments have been approved giving men more options.

Hormone (Androgen Deprivation) Therapies

Bilateral orchiectomy is an operation that removes both testicles, which produce 95% of the body's testosterone.

Advantages of Orchiectomy

  • One-time procedure
  • Effective, permanent reduction in testosterone
  • No hospitalization
  • Low Cost

Disadvantages of Orchiectomy

  • Side effects, such as reduced or absent sexual desire, impotence, and hot flashes and emotional impact make this procedure difficult for some patients to accept, although side effects are the same as with medical castration
  • Irreversible surgical procedure
  • May require hospitalization in some patients
  • Will not allow for intermittent androgen deprivation (IAD) therapy

LHRH Therapy is the administration of an injectable luteinizing hormone-releasing hormone (LHRH) agonist or antagonist that causes a drop in testosterone levels in the body, which lowers the ability to produce testosterone.

Advantages of LHRH Agonists

  • Easy administration of injections every 1, 3, 4, 6 or 12 months
  • Treatment with LHRH agonists almost always as effective as orchiectomy in reducing testosterone levels
  • Side effects may be reversible upon termination of the treatment so as to allow IAD therapy

Disadvantages of LHRH Agonists

  • Side effects of hormone therapy may be difficult to treat and hard for some people to accept
  • Testosterone level rises during first two weeks of initiating therapy (flare response), which may cause increase in cancer symptoms in some men
  • Requires injections every 1, 3, 4, 6, or 12 months
  • May need short-term anti-androgen to reduce risk of flare response

Currently available LHRH agonists in U.S.:

  • Lupron® (leuprolide acetate)
  • Eligard® (leuprolide acetate)
  • Viadur® (leuprolide acetate implant)
  • Vantas® (histrelin implant)
  • Zoladex® (goserelin acetate)
  • Trelstar™ (triptorelin)

Advantages of LHRH Antagonist

  • Reduces testosterone levels quickly without the initial "testosterone surge" seen with an LHRH agonist
  • Antiandrogen therapy is not needed to prevent possible flare symptoms
  • Easy subcutaneous (just under the abdomen skin) injections

Disadvantages of LHRH Antagonist

  • Side effects of hormone therapy may be difficult to treat and hard for some people to accept
  • Overall rate of adverse reactions is similar to LHRH agonists
  • Injection site discomfort
  • Currently only monthly injection available

Currently available LHRH antagonists

  • Firmagon (Degarelix)

Antiandrogen Therapy

Antiandrogen Therapy includes orally administered drugs that block the action of male hormones, including testosterone and androgens released by the adrenal glands or produced by prostate cancer cells. First generation anti-androgens were often used in combination with LHRH agonist therapy in a strategy called maximal androgen blockade (MAB) or combined androgen blockade (CAB). Some studies showed longer survival with MAB compared to ADT alone. The anti-androgen is continued until the PSA rises. When the PSA rises, stopping the anti-androgen can result in a short-term benefit. Second generation anti-androgens have been approved which improve survival and are also being tested in combination with castration. You can read or join discussions about CAB at the CHB bulletin board. With the approval of the newer anti-androgens, first generation drugs are no longer used as early in the management of advanced disease. The newer anti-androgens include enzalutamide, abiraterone acetate (in combination with prednisone), apalutamide and darolutamide. Enzalutamide has been approved thus far for two groups of patients. First, for men with non-metastatic disease (nmCRPC) that is no longer responding to castration and second, for men with metastatic disease that no longer responds to castration (mCRPC). In both cases survival is improved. Abiraterone acetate also has FDA approval for patients with metastatic high-risk castration-sensitive prostate cancer in combination with androgen deprivation and for metastatic castration resistant disease. Apalutamide was approved in combination with castration both for men with non-metastatic castrate resistant disease and because it delayed metastases and for men with metastatic castration sensitive disease (mCSPC) because it improved overall survival. Darolutamide has been approved for castration resistant non-metastatic disease because it delayed the time to developing metastases.

Advantages of First Generation Antiandrogen Therapy

  • Fewer side effects than LHRH therapy
  • Administered by mouth

Disadvantages of First Generation Antiandrogen Therapy

  • Breast pain or enlargement
  • Diarrhea
  • Gastrointestinal pain
  • Adverse effects on liver function (possible elevation of liver enzymes that must be monitored)
  • Night blindness (niutamide)

First Generation Antiandrogens Available in the U.S.:

  • Improve survival and/or delay time to metastatic disease when used with castration

Second Generation Antiandrogens Available in the U.S.

  • Xtandi (enzalutamide)
  • Zytiga (abiraterone acetate) in combination with prednisone
  • Erleada (apalutamide)
  • Nubeqa (darolutamide)

Estrogen Therapy

Administration of estrogen hormones lowers testosterone production and has some direct apoptotic effects on both androgen-dependent and androgen-independent prostate cancer cells.

Currently available estrogen therapies:

  • DES (diethylstilbestrol)
  • Stilphosterol® (stilbestrol diphosphate)
  • Estraderm® patch (estradiol) – only one small-scale trial has investigated the benefits of delivering estrogen through the skin (transdermal) to block testosterone production in men with prostate cancer. In that study, the patch was successful in reducing testosterone levels, with fewer cardiovascular or other side effects (gynomastia). Phase III trials are currently comparing the effects of patch and injected forms of estrogen in men with prostate cancer.

Advantages of Estrogen Therapy

  • Does not cause bone loss
  • Dose not induce androgen-independent cancer growth
  • Can dramatically slow the growth of some prostate cancer cell types
  • Inexpensive

Disadvantages of Estrogen Therapy

  • Will cause gynecomastia, unless prevented by breast irradiation
  • Depending on the route of administration, it may promote hypercoagulation of blood, causing blood clots in the legs, lungs, heart, and brain
  • May cause heart attacks
  • No evidence that blood thinners significantly reduce risk of clots
  • Causes decreased libido and impotence
  • Risk of cardiovascular side effects is reduced when treatment is given as patch or injectable drug rather than by mouth

Autologous Cellular Immunotherapy

The goal of this therapy is to stimulate the body’s immune system to attack cancer cells. The only approved immunotherapy for prostate cancer is Provenge® (sipuleucel-T). It is indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. Provenge is given by intravenous (IV) infusion in three doses, approximately two weeks apart over the span of a month. Blood is collected a few days prior to each infusion, processed at an outside laboratory and then returned to the patient by intravenous infusion. Total course of therapy is generally completed in four to six weeks.

Advantages

  • Minimal typical side effects compared to other treatment options
  • Prolongs survival of men with CRPC
  • Does not interfere with effectiveness of other therapies
  • Therapy completed quickly

Disadvantages

  • The most common side effects reported with Provenge treatment (usually occurring within the first few days of treatment) are: chills, fatigue, fever, back pain, nausea, joint ache and headache; other side effects are also possible
  • In a very small number of men, Provenge can cause severe acute reactions resulting from the infusion, which typically occur within one day of infusion
  • Does not lower PSA or produce measurable objective response
  • Costly, but covered by most insurance companies, including Medicare

For more information on Provenge, visit www.Provenge.com.

Other Drugs

P450 Enzyme Inhibitors

The P450 enzymes are involved in the synthesis of several hormones, including testosterone, that stimulate prostate cancer cell growth. Inhibitors of these enzymes can decrease the levels of testosterone and adrenal androgens, and have direct cytotoxic effects on prostate cancer cells. Although not specifically approved for men with prostate cancer, they were used for men progressing on castration therapy but are seldom used today.

Available P450 enzyme inhibitors:

  • Nizoral® (ketoconazole used in combination with hydrocortisone)

Advantages of P450 Enzyme Inhibitors

  • May still be useful in men for whom CAB has failed (who are androgen resistant)
  • Reduces both testicular testosterone and adrenal androgen production
  • Additional cytotoxic effect on prostate cancer cells

Disadvantages of P450 Enzyme Inhibitors

  • Not approved in U.S. for treatment of prostate cancer
  • Requires continued use of LHRH agonists or estrogen therapy to block pituitary stimulation of testicular hormone production (unless the patient had an orchiectomy)
  • Non-selective effects on other cells may cause discomfort (nausea, gastric irritation)
  • May have significant adverse effects on liver function (must measure liver enzymes)

5-alpha Reductase (5-AR) Inhibitors

Block conversion of testosterone to DHT, a more potent stimulator of prostate cell growth than testosterone. May delay rise in PSA. Not currently approved for use in men with prostate cancer.

Currently available 5-AR inhibitors:

  • Proscar®, Propecia® (finasteride) – reduces DHT levels in the blood by 70% and 80%-90% on prostate
  • Avodart® (dutasteride)– reduces DHT levels in the blood by 98% and can slow prostate cell growth

Advantages of 5-AR Inhibitors

  • Reduces the normal prostate cell growth and prostate size
  • May reduce the risk of recurrence following surgery

Disadvantages of 5-AR Inhibitors

  • Not approved as a treatment for prostate cancer
  • No evidence it influences survival of men
  • Causes only modest reductions in PSA levels (15-20%) when used alone

Systemic Radiation Therapy

These agents are injected intravenously and are taken up by cancer cells that have invaded into the bones. Only Xofigo® (Radium-223) has been shown to significantly improve survival.

Advantages

  • Treatment administered as a one-time injection
  • Significantly improves survival in men with symptomatic bone metastases
  • Patients still eligible for chemotherapy

Disadvantages

  • Side effects include nausea, vomiting, diarrhea, low blood counts

See the sections on radiation therapy and treating pain associated with advanced prostate cancer for more details

For more information on Xofigo, visit Xofigo.com.

Currently Available Radiopharmaceuticals

  • Xofigo (Radium-223)
  • Metastron (Strontium-89)
  • Quadramet (Samarium-153)

Chemotherapy

The administration of powerful toxic drugs that circulate throughout the body and eliminate rapidly growing cancer cells. It can also affect rapidly growing healthy cells, which can lead to side effects. Primarily used in patients with advanced stage cancer ( Stage M+) that is no longer responding to androgen deprivation therapy and anti-androgens, however recent studies show that combining docetaxel with androgen deprivation in high risk newly diagnosed metastatic disease improves survival compared to delayed chemotherapy.

Advantages of Chemotherapy

  • May prolong survival
  • Provides cancer symptom improvement

Disadvantages of Chemotherapy

  • Hair loss
  • Nausea
  • Vomiting
  • Diarrhea
  • Anemia
  • Reduced blood clotting
  • Increased risk of infection
  • Lowered white cell count

Currently Available Chemotherapy Drugs

  • Taxotere® (docetaxel)- Phase III randomized studies have shown that Taxotere in combination with prednisone can significantly improve survival on average by 2 months in patients with hormone resistant prostate cancer
  • Jevtana®(cabazitaxel) - indicated in combination with prednisone for the treatment of patients with metastatic hormone-refractory prostate cancer (mHRPC) previously treated with a docetaxel-based treatment regimen
  • Novantrone® (mitoxantrone) specifically approved for hormone resistant prostate cancer. Studies show it improves quality of life but does not increase survival
  • Emcyt® (estramustine)

Summary

Treatment options for men with metastatic disease have increased in the past several years and provide men with a significantly longer survival compared to 5-10 years ago. The challenge today is to determine the right timing and sequencing of the newly available options.

Hormone-Resistant Prostate Cancer

Prostate cancer that is no longer responsive to hormone therapy is referred to as hormone-resistant prostate cancer, hormone refractory prostate cancer (HRPC), castrate resistant prostate cancer (CRPC) or androgen-independent prostate cancer. Several new therapies have been approved in the past several years to treat CRPC. More studies are needed to determine the optimal sequencing of these new treatments.

Zytiga® (Abiraterone Acetate)

Oral agent that has been approved in combination with prednisone for CRPC. It acts by inhibiting an enzyme complex called CYP-17 that is necessary for producing testosterone. Studies show that this enzyme is present in the adrenal gland and in prostate cancer cells.

Advantages

  • Oral agent
  • Prolongs survival in men with CRPC

Disadvantages

  • Must be given with prednisone
  • Must be taken on an empty stomach
  • Costly
  • Side effects occur including hypertension, increased potassium level and fluid retention

For more information about Zytiga, visit zytiga.com.

XTANDI® (Enzalutamide)

Oral agent that has been approved for men with CRPC after they progress on chemotherapy. The FDA is currently considering an approval for men prior to chemotherapy. It works by interfering with androgen receptor signaling in prostate cancer cells.

Advantages

  • Oral Agent
  • Prolongs survival

Disadvantages

  • Side effects can occur including asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain
  • Costly
  • May increase risk of seizures

For more information about XTANDI, visit xtandi.com.