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Patient's Guide to Prostate Cancer: Treatments

Deciding how to treat prostate cancer can be a confusing process. Each of the treatments has its own mix of benefits, risks and impacts on quality of life. The good news is that several treatments are very successful for a great many prostate cancer patients, either in providing a cure or keeping the cancer under control for many years.

Choosing the treatment that is right for you is influenced by a number of factors, including:

  • The stage and grade of the cancer
  • Your age
  • Your general health and specific medical conditions
  • Life expectancy
  • Cost and practical considerations
  • Attitudes about cure and/or living with cancer
  • Your needs, concerns, values and social relationships

Determining whether or not the cancer is confined to the prostate is a crucial factor in choosing a treatment:

  • If the cancer is confined to the organ, then a localized treatment that attempts a cure is considered. Options include: a radical prostatectomy that removes the organ; one of the forms of radiation therapy to shrink or kill the tumor; or cryosurgery, which uses extreme cold to kill cancer cells.
  • If the cancer has spread, either locally to nearby lymph nodes or more distantly to bones or other organs, then the goal of treatment may be to control the cancer rather than to cure it.

In many cases, it is difficult to know definitively whether or not the cancer is confined to the prostate. This uncertainty may arise in cases when the cancer is at a higher stage (T2b or above), and/or has a Gleason score of 7 or more, and/or has a pre-treatment PSA above 10.

One of the commonly used methods to determine the likelihood of cancer spread is to use a table, which combines the information on staging to produce a score indicating the odds of the cancer being confined to the organ or having spread. The most commonly used tables are the Partin table and Kattan nomogram. They can be obtained from various Internet sites and also from books and journal articles.

Although helpful, these tables are based on results from large numbers of people, and may not reflect your specific condition. Since there is a greater likelihood of recurrence with higher-risk cancers if a single localized treatment method is used, combined treatments, such as radiation therapy and hormone therapy together, may be considered.

No matter which treatments you choose, it's important to monitor your PSA regularly.

Radical Prostatectomy

This operation removes the entire prostate gland plus some surrounding tissue, and is used most often when the cancer is thought not to have spread far outside the gland. The surgery is done under general anesthesia, generally takes two to four hours and requires a hospital stay of two to three days.

There are three main types of radical prostatectomy, which are described in this patient education article, along with details on the procedure.

Radical prostatectomy has been performed successfully for many years. For a long time, prostatectomy was regarded as the "gold standard" of prostate cancer treatment although other techniques have yielded similarly good results. However, there is still no guarantee that the cancer will not return. Some cancers are found to be more extensive or aggressive than was thought before the operation, which indicates a higher risk for cancer recurrence. The value of a prostatectomy is that the primary tumor is removed and more accurate staging of the cancer can be done.

The main risks of these prostatectomy procedures are impotence — a complete or partial inability to have an erection without assistance — and urinary incontinence. The skill and experience of the surgeon is an important factor in how frequently these occur.

Most men experience some degree of erectile dysfunction in the three- to 36-month period following the surgery. After a non-nerve sparing radical prostatectomy, approximately 90 percent of men become impotent. With the nerve-sparing procedure, the impotence rate drops to between 25 percent and 30 percent for men under age 60. Various medications (such as Viagra), certain procedures and counseling have helped men deal with post-surgical erectile dysfunction. Even with recovery of potency, the resulting orgasms will be dry because there is no prostate gland left to produce fluid for the ejaculate.

Nearly everyone will experience some temporary incontinence immediately after surgery. Normal bladder control usually returns within several weeks or a few months. Anywhere from 1 percent to 5 percent of patients have permanent stress incontinence (passing urine after coughing, laughing, sneezing or exercising) or general difficulty controlling urine flow. Certain exercises known as Kegel exercises, as well as recently refined surgical procedures, may improve or restore bladder control.

Radiation Therapy

Radiation therapy uses high-energy rays and particles to kill cancer cells. There are two main types, described below

External Beam Radiation Therapy

Radiation, usually in the form of X-rays, is focused from a source outside the body on the area affected by the cancer. After imaging studies are done to locate the cancer in relation to the surrounding structures and organs, a treatment plan is designed to guide where the radiation beams will be directed. Marks are placed on the patient's skin to help position the patient for treatment. Patients are treated five days per week in an outpatient center over a period of seven to eight weeks, with each treatment lasting only a few minutes.

The side effects of external beam radiation therapy can include diarrhea, frequent urination, a burning sensation while urinating and rarely blood in the urine. These symptoms disappear or significantly lessen over time. Patients also may experience fatigue, which can last for a month or two after treatment stops. About 40 percent to 60 percent of men who receive external beam radiation therapy may develop some degree of impotence one or more years after the treatment. The risk might be higher if they receive hormonal treatment.

3D Conformal Radiation Therapy is a state-of-the-art form of external beam radiation therapy that uses a sophisticated computer program to map the prostate gland more precisely to pinpoint radiation beams from up to six or seven different directions. An external mold cast keeps the patient still. This more accurate aiming from multiple sources makes it possible to reduce the radiation received by nearby tissues while concentrating the radiation dose at the cancer site.

An even more advanced development of this method, intensity modulated radiation therapy (IMRT), can vary the intensity of the radiation beams. Another improvement involves placing gold seeds into the prostate to help increase the accuracy of the external beams.

Proton Beam radiation therapy, using protons rather than X-rays, is presently available at only a few centers in this country. Studies have shown that proton beam therapy is effective in treating localized prostate cancer. However, the data is inconclusive as to whether proton therapy yields better outcomes than X-ray therapy.

Brachytherapy

There are two forms of this treatment. In a permanent seed implant (SI), small radioactive pellets, often called "seeds," each about the size of a grain of rice, are implanted into the prostate. These seed implants contain radioactive isotopes such as iodine 125 or palladium 103. They are left permanently in the prostate and give off radiation for periods of weeks or months.

This is an outpatient procedure. Imaging tests such as a transrectal ultrasound or an MRI are used to accurately guide the placement of the radioactive material into the prostate. The seeds are placed inside thin needles inserted through the skin of the perineum, the area between the scrotum and anus. Their location within the prostate is determined with the aid of a computer program.

In the temporary method, called high-dose rate brachytherapy (HDR), the radioactive material, such as iridium, is placed in the inserted needles for relatively short periods of time and then withdrawn from the prostate. There usually are two to three treatments administered over one to two days in a hospital.

A permanent seed implant can be done only on a prostate gland that is not too enlarged. In many cases, a course of hormone therapy may reduce the size of the gland sufficiently to make the implant procedure safer. Hormone therapy can be used together with brachytherapy or with external beam radiation therapy to enhance treatment effectiveness. Similarly, brachytherapy has been combined with external beam radiation therapy to improve treatment outcome, particularly in cases where there may be some spread to local tissues and/or the Gleason score is somewhat elevated. Many treatment centers that undertake brachytherapy are now generally restricting its use as a single treatment to patients with PSA scores under 10 and Gleason scores of 6 or less.

The effectiveness of brachytherapy and external beam radiation therapy is indicated by the extent of decline of the PSA. The lowest level of the PSA that is attained is referred to as the nadir. The lower the nadir the better. Doctors look for a nadir of as much below a PSA of 1.0 as possible. It may take one to three years after radiation therapy to reach a nadir. About one-third of men who have undergone brachytherapy experience a temporary "spike" or "bounce" in their PSA scores 12 to 24 months after the procedure before the score resumes its continuing decline. Such a spike shouldn't be interpreted as treatment failure.

Many men experience some short-term side effects from brachytherapy, such as perineal pain, discolored urine or urinary problems such as slow starting, incomplete emptying or increased frequency. Erectile dysfunction may develop over a more extended period of time. A small percentage will experience varying degrees of urinary incontinence or significant rectal or bowel problems.

Cryosurgery

Cryosurgery, used to treat localized prostate cancer, kills the cancer cells in the prostate by freezing them. Probes containing liquid nitrogen are inserted into the prostate gland and are maneuvered under ultrasound guidance to destroy prostate tissue. This method has shown good results in treating cancer confined to the prostate, but is presently performed at a limited number of locations around the country.

Some doctors maintain that to be maximally effective, the entire prostate must be frozen, which impacts the nerve bundles on the sides of the gland. Consequently, impotence almost always results from cryosurgery when the entire gland is treated. Urinary incontinence also may occur. Some doctors are performing "nerve-sparing" cryotherapy, where only the cancerous area of the prostate is treated.

Hormone Therapy

Hormone therapy is based on the finding that prostate cancer cells usually require testosterone, the main male hormone or androgen, to grow. Therefore, lowering androgen levels can stop or slow cancer growth.

Hormone therapy may control the cancer, often for a number of years, but it is not a cure. Usually, the cancer will change over time into a form that no longer needs testosterone to grow. When the cancer no longer requires testosterone to grow, it is called androgen independent, and other treatments must be considered.

Most prostate cancers are very responsive to hormone therapy when first diagnosed. Hormone therapy usually is recommended as the initial treatment for advanced prostate cancers, including prostate cancers that have metastasized. Hormone therapy does have significant side effects, and the decision to undergo it should not be made casually.

In the past, there were two main approaches to hormone therapy. One was the surgical procedure of orchiectomy, which removed the testes, the main source of androgens in men. This is an effective hormonal treatment but it is permanent, and some men have to cope with the psychological consequences of the loss of their testes. The second approach involves giving estrogen compounds, such as diethylstilbesterol (DES), to reduce testosterone levels. Using estrogens may cause side effects such as breast enlargement and weight gain, as well as a slight increase in the risk of heart attacks and strokes.

Presently, hormone therapy usually uses a combination of two different types of medication. One type is called a luteinizing hormone-releasing hormone (LHRH) analog or agonist. This modifies the body's hormone control system to cause the testes to shut down testosterone production.

The effect is equivalent to an orchiectomy. These analogs are put into a time-release preparation that is injected into the muscle or inserted under the skin at periodic intervals.

The two luteinizing hormone-releasing hormone analogs available in this country are leuprolide (Lupron) and goserelin (Zoladex). The luteinizing hormone-releasing hormone agonists cause a temporary increase or "flare" in testosterone when first administered, which may be troublesome for some men, particularly those with more advanced or metastatic cancer. An anti-androgen (see below) should be started a week prior to giving the LHRH agonist to block the effects of this flare.

The second type of medication is called an anti-androgen. Even after testicular production is shut down, a small amount of androgen is still produced by the adrenal glands. Anti-androgens block the ability of prostate tissue to use androgens. Anti-androgens include flutamide (Eulexin), bicalutamide (Casodex) and nilutamide (Nilandron), which are taken as pills one to three times a day.

This combination of the two types of medications is called total androgen blockade or combined androgen blockade. There is controversy about whether anti-androgens need to be used with the luteinizing hormone-releasing hormone analogs; studies have produced mixed results. Also controversial is the use of a third medication as part of the hormone therapy mix called finasteride (Proscar), which is commonly used to treat benign prostatic hyperplasia.

Finasteride blocks the enzyme that converts other androgens to dihydrotestosterone (DHT), the most active form of testosterone in stimulating the growth of both normal and cancerous prostate cells.

The primary side effects of hormonal therapy are related to lowering of the body's testosterone levels. Most men experience a decrease in sexual desire and some level of erectile dysfunction. Working cooperatively with your partner to accommodate the changes resulting from hormone therapy and other treatments can help you remain sexually active. Various medications, as well as some mechanical methods, may help restore potency.

Some men experience breast tenderness and breast tissue growth. Hot flashes are common, but often reduce in frequency or intensity over time or disappear almost completely. Hot flashes can be treated with different medications, and, in some cases, certain soy products can be helpful.

In some men, hormone therapy causes fatigue, lower energy and reduced muscle mass. Patients who are on hormone therapy for more than two or three years risk developing osteoporosis, a thinning of the bones caused by a loss of calcium.

Medications are available to reduce your risk of osteoporosis. Be sure to ask your doctor about them. Bone density examinations are advisable and treatment should be undertaken if a significant reduction in density is found. A regular exercise program is also of value.

The anti-androgens may also, in some cases, cause nausea, diarrhea and fatigue — occasionally severe enough to require discontinuing the medication. Stopping anti-androgens is necessary in the small percentage of men whose liver function is affected or whose blood pressure becomes very high.

Intermittent Hormone Therapy

In this approach, also called intermittent androgen blockade, a patient is placed on hormone therapy for a period of some months to a year or more. After the PSA level has dropped close to zero and remains at this level, the hormone therapy is stopped. When the PSA rises to a certain level following the return of testosterone production, the hormone therapy is resumed. The length of time that a man can stay off treatment can range from several months to well over a year.

There is presently no clear consensus as to what PSA levels should be used to restart the hormone therapy, or how long the periods of either the initial treatment or the resumption of treatment should be. A number of men using this approach have been able to go through six or more on-off rounds, for up to seven or more years, with the treatment retaining its effectiveness.

The intermittent approach may reduce some of the side effects of hormone therapy, improve quality of life and allow some men to regain their sexual interest and potency during the off period. This method is regarded as experimental. Studies are being conducted to compare its effectiveness with continuous hormone therapy and to ascertain if it delays androgen independence.

The continued rise of the PSA while the patient is on hormone therapy is the main indicator that the treatment is losing its effectiveness. At this point, other "second line" hormonal treatments can be considered. Some men who are on combined androgen blockade will experience a reduced PSA when the anti-androgen medication is stopped. This reduction usually is only temporary, lasting for several months.

Ketoconazole (Nizoral), which shuts down hormonal production by the adrenal glands and requires supplementary hydrocortisone when it is used, has shown sustained effectiveness in controlling advanced prostate cancer. Aminogluthamide also is used for this purpose, as are some estrogenic compounds.

PC-SPES, a standardized preparation of eight herbs, has shown positive results in controlled studies with both androgen-dependent and androgen-independent cancers. It is not known exactly how it works, but its effectiveness may result in part from its estrogenic properties. Cardiovascular risks such as blood clots are associated with it, so a physician should monitor its use. Recently, analysis of various samples of the PC-SPES revealed the presence of small amounts of biologically active substances that could pose additional risks. At present, PCSPES is no longer produced in the United States.

Chemotherapy

Chemotherapy drugs are commonly used to treat many different cancers. They kill cancer cells directly, usually by disrupting the reproductive cycle of those cells. But they also damage normal cells and can cause significant side effects, such as nausea, hair loss, loss of appetite, fatigue and low blood cell counts. While these side effects generally disappear after treatment is stopped, they can be debilitating and seriously affect quality of life.

Chemotherapy usually is used with patients whose prostate cancer has metastasized outside the prostate and for whom hormone therapy has failed. In the past, chemotherapy has shown only limited effectiveness in treating advanced prostate cancer. More recently, new developments in this approach — such as giving two or more drugs together, using newly developed chemotherapy agents, and combining chemotherapy with hormone therapy — have significantly improved treatment outcomes.

Active Surveillance

Some prostate cancer patients don't pursue any active treatment and instead use a "watch and wait" approach, also known as active surveillance, which involves extensive monitoring. This may be recommended if the cancer is very small and confined to one area of the prostate; is expected to grow very slowly; or if the patient is elderly, frail or has other serious health problems.

Since prostate cancer tends to grow very slowly, older men with the disease may never need treatment. Younger patients, or those with a life expectancy greater than 10 years, may need a more aggressive approach. The best candidates for this regimen are those with small, low grade cancers associated with low and stable PSA levels.

Some men may decide that the side effects of more aggressive treatments outweigh the benefits and they turn to alternative therapies to slow cancer development. In these cases, close monitoring is critical so if the cancer develops into a more serious form, it is immediately detected.

More than 500 patients at the UCSF Prostate Cancer Center have chosen active surveillance. About one in five on active surveillance receive treatment two to three years after diagnosis, after a change is detected such as a rapidly rising PSA level or increased tumor size.

At UCSF, men on active surveillance have PSA levels checked every three to four months, prostate ultrasounds every six to nine months and prostate biopsies after one year of active surveillance, then again every one to two years.

For more information, listen to a Patient Power interview about active surveillance with Dr. Peter Carroll.

New Treatment Approaches and Clinical Trials

Research done in recent years has substantially increased our understanding of cancer generally, and prostate cancer specifically. A number of new treatments have been developed and are being tested in cancer patients.

Presently, clinical trials are being conducted primarily with prostate cancer patients who have rising PSAs after local treatment or who have more advanced, metastatic cancers. A number of the new agents already are showing effectiveness and may eventually provide more treatment options for new and recurring cancers. However, at this time, none of them can be regarded as cures, or even as replacements for surgery, radiation or hormone therapy.

Generally, patients being treated with these new approaches have experienced fewer side effects than patients getting more traditional treatments.

There are three main phases of these studies:

  • Phase I studies try to determine safe and therapeutic dosage levels with relatively small numbers of patients
  • Phase II trials have more patients to determine whether the new agent is beneficial
  • Phase III trials have a large group of patients who receive the experimental treatment and the results are compared with results from a control group receiving standard therapy

Clinical trials are conducted at local cancer centers, including the UCSF Helen Diller Family Comprehensive Cancer Center, as well as at centers all around the country, and participants often are actively recruited. Clinical trials can offer hope but have their risks as well. Any patient considering participating in a trial should ask a number of questions, such as:

  • Do I fit the criteria for inclusion?
  • How might I benefit from participating?
  • What are the probable side effects?
  • What if I'm placed in the control group that doesn't get the treatment or medication?

Some promising new approaches for treating prostate cancer include the following.

Dendritic Cell Vaccine

Dendritic cells in the blood identify foreign cells or organisms that should be attacked by the killer cells of the immune system. In the vaccine approach, dendritic cells are taken from the bloodstream and exposed to the prostate cancer cells. This exposure to the cancer cells makes it easier for the dendritic cells to identify cancer cells in the body. After this procedure, the dendritic cells are inserted back into the blood stream to target prostate cancer cells for immune system action.

Monoclonal Antibodies

These are agents that are developed to trigger an immune system response by targeting antigens that are present on the surface of prostate cancer cells.

Genetically Engineered Viruses

Viruses such as the common cold virus are genetically modified to target prostate cancer cells. These viruses can be injected directly into the prostate or into metastatic tumors.

Chemotherapy

A traditional chemotherapy drug can be combined with a protein-like compound and is released only when it comes in contact with prostate cancer cells, selectively targeting them for attack.

Anti-Angiogenesis

At some point, cancers need to develop a blood supply if they are to grow. New agents are being developed and tested for their effectiveness in retarding the growth of blood vessels in tumors.

Radiation Therapy

There are trials to evaluate modifications in the delivery of radiation therapy, or to discover how radiation therapy can be combined with other therapies to more effectively treat higher-risk prostate cancers.

Diet and Life Style Changes

Dr. Dean Ornish, who developed a program that successfully treats serious cardiovascular disease, is studying whether a similar program can slow or reverse early-stage prostate cancer. The program includes: adhering to a very low fat, vegetarian diet; nutritional supplements; regular exercise; stress reduction and group support.

Alternative and Complementary Therapies

Alternative and complementary therapies refer to treatments that fall outside the conventional model of medicine typically used in this country. Their effectiveness for treating cancer is, as yet, unproven. The field of alternative and complementary medicine is very broad and encompasses changes in diet, stress reduction and life style changes, acupuncture, homeopathy and other approaches.

There is an important distinction between "complementary" and "alternative." Complementary therapies are undertaken in addition to conventional medical treatment, and may be more often encouraged by medical treatment personnel. Alternative therapies are undertaken instead of conventional medical treatment. They therefore have more risks associated with their use and should be used with more caution.

Many therapies can fall into either category. Some interfere with standard medical treatment or cause serious side effects, and patients' doctors should be fully informed of their use. But many of these therapies can benefit patients by helping them lead more healthy and active lives, reducing emotional stress associated with prostate cancer and its treatment, and reducing pain and discomfort.

The main alternative and complementary therapies are discussed below.

Diet, Nutrition and Supplements

There is a broad consensus that diets high in fat, especially animal fat, increase the likelihood of developing prostate cancer. Some people believe that reducing the amount of fat in your diet may slow cancer growth, but there is no agreement as to how much of a reduction in fat intake is needed. Some men choose to eat less meat and dairy products while continuing to eat poultry or fish, while others become vegetarians. It is still important for the diet to be properly balanced. While many men have readily made major changes in what they eat, changing one's diet isn't easy and may require the cooperation of family and friends.

Many substances, preparations, supplements and herbs are touted as being effective in fighting or even curing cancer without any evidence to support such claims. Use caution when using unproven treatments and share the information with your physician.

Substances showing promise, but with little documented evidence, are lycopenes, which are found in high amounts in tomato products; green tea; and soy foods. In moderation, these substances generally aren't harmful. There is some indication that the whole food may be more effective than the extracts offered in supplements.

A nutrition consultation with a professional can be very informative, and can be arranged through the Cancer Resource Center if you are a UCSF Medical Center patient. As always, let your physician know about dietary changes and the supplements you take.

Exercise

Being physically active is not only good for the body, it also relieves depression and promotes a sense of well-being. Exercise doesn't have to be aerobic or so intense as to lead to pain or exhaustion to be of help. Just taking a walk for up to an hour three times a week can provide benefit.

Stress Reduction

A wide array of activities can help reduce stress and anxiety. These include various meditation practices, modifying your breathing rhythm, visualization, relaxation exercises and massage. Classes and groups are available to teach these techniques. The UCSF Cancer Resource Center can direct you to information and resources.

A cancer diagnosis can lead to an examination of one's life and how it is lived, resulting in changes in work, play, relationships, personal and social behaviors, and spiritual practices that can accentuate the positive and reduce the more stressful and negative aspects of one's daily life.

Asian Medicine

There is a growing interest in the treatment and meditative practices used and developed over hundreds of years in certain Asian countries, particularly China. Acupuncture has become increasingly accepted by Western medicine, and has been effective in reducing the pain and discomfort associated with various medical conditions. Stylized movements and exercises such as tai chi, qigong and yoga can help people feel more balanced and more at ease with themselves. Traditional Chinese medicine uses herbal preparations to treat a variety of disorders, including prostate cancer. Some of these treatments are being studied systematically in the United States.

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Reviewed by health care specialists at UCSF Medical Center.

This information is for educational purposes only and is not intended to replace the advice of your doctor or health care provider. We encourage you to discuss with your doctor any questions or concerns you may have.

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Prostate Cancer Center
1600 Divisadero St., Third Floor
San Francisco, CA 94115
Phone: (415) 353-7171
Fax: (415) 353-7093

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