Patient information: Prostate cancer treatment; early stage cancer

PROSTATE CANCER OVERVIEW

Prostate cancer is a cancer of the prostate gland, an organ that forms a ring around the urethra, near its connection to the bladder (figure 1). The urethra is the tube that carries urine from the bladder to the outside of the body.

Prostate cancer is the most common cancer affecting men. Every year, more than 200,000 American men are diagnosed with prostate cancer, and nearly 30,000 die from this disease. Over the last 15 years, prostate cancer screening has led to more men being diagnosed at an early stage, when the cancer is still limited to the prostate gland and is highly curable.

There are three standard approaches to treating early prostate cancer: surgery to remove the prostate gland, radiation therapy with or without hormone therapy, and "active surveillance".

This article discusses the available treatment options for prostate cancer, outcomes from therapy, and treatment-related side effects. A summary to guide your choice between treatments is available below (see 'Summary: Choosing the right prostate cancer treatment' below. Advanced prostate cancer and diagnosis and staging of prostate cancer are discussed separately. (See "Patient information: Prostate cancer treatment; advanced cancer" and "Patient information: Prostate cancer diagnosis and staging".)

STANDARD PROSTATE CANCER TREATMENT OPTIONS

The three standard therapies for men with organ-confined prostate cancer are:

• Surgery (radical prostatectomy)
• Radiation therapy
• Active surveillance (also called watchful waiting)

Radical prostatectomy — Radical prostatectomy (also called prostatectomy) is a surgery done to remove the prostate gland and then reconnect the urethra and bladder (figure 1). This treatment is thought to offer the best chance for long-term survival (beyond ten years).

Complications — The most common complications of prostatectomy are:

• Urinary incontinence (leakage of urine) and
• Erectile dysfunction (ED, the inability to have an erection sufficient for sexual intercourse).

Most men have some degree of urinary incontinence and ED immediately following surgery, although both usually improve over time. (See "Patient information: Sexual problems in men".)

Nerve sparing procedures — A surgery that avoids the nerves responsible for urinary and sexual function (called nerve-sparing prostatectomy) can reduce the risk of developing urinary incontinence and erectile dysfunction after surgery. However, this procedure may not be possible for men with large tumors, high Gleason grade cancers, or a high PSA before treatment.

Radiation therapy (RT) — Two forms of RT are used to treat prostate cancer: external beam RT and interstitial implantation, also called brachytherapy. These are sometimes used together.

External beam radiation — External beam RT (EBRT) uses a machine that moves around the patient, directing x-rays (also called gamma rays) at the pelvis. EBRT is typically done daily five days per week and lasts five to eight weeks. Each treatment with EBRT takes just a few minutes, and you can usually continue your normal activities during treatment.

• Complications — Possible side effects of EBRT include urinary urgency and/or frequency, bladder pain, sexual impotence (erectile dysfunction, ED), and bowel problems such as proctitis (inflammation of the rectum). Compared to prostatectomy, urinary problems and ED are less common following radiation therapy, but bowel problems such as diarrhea, bowel urgency, and painful hemorrhoids are more common. In contrast to men who have surgery, ED rates increase over time after radiation therapy.

These differences in treatment-related complications continue to be evident up to five year following treatment [1,2]. Medicines for erectile dysfunction may be beneficial for men with radiation-related problems. (See "Patient information: Sexual problems in men".)

Conformal radiation — Three-dimensional conformal radiation therapy, or 3D-CRT, uses sophisticated computer modeling to precisely outline the tumor and deliver larger doses of RT while minimizing damage to surrounding normal tissues. This technique is more expensive than EBRT, and has not been proven more effective than conventional RT. However, it may have fewer side effects (particularly bowel problems) and it may be able to deliver a higher dose of radiation to the prostate.

Intensity modulated radiation therapy — Intensity modulated radiation therapy (IMRT) is an advanced form of 3D-CRT in which the radiation dose to the prostate gland, a complex and irregular target, is varied by changing the intensity of the beam during therapy. The major advantage of IMRT over 3D-CRT is a reduction in the dose received by nearby organs, particularly the bowel, resulting in fewer side effects. The advantage may be greatest in men who require RT of the pelvic lymph nodes in addition to the prostate gland. IMRT requires special expertise and equipment, and is becoming more available in treatment centers within the United States.

Brachytherapy — Brachytherapy involves placing a radioactive source directly into the prostate gland. The procedure is done with anesthesia. There are two types of brachytherapy.

• Low-dose-rate (LDR) brachytherapy implants rice-sized radioactive seeds or pellets into the prostate, which emit radiation from within the gland. The seeds gradually lose their radioactivity over time and are not removed. The dose of radiation to surrounding tissues is limited.

Some men have questions or fears about the possibility of exposing family members to unsafe levels of radiation. Most men are advised to avoid prolonged, direct contact with children and pregnant women (eg, by sitting on the patient's lap) for three months after seed placement.

• High-dose rate (HDR) brachytherapy uses a catheter or needle inserted into the prostate to temporarily implant a radioactive source into the prostate gland over a period of several hours. The catheter or needle is placed while a patient is under general anesthesia, but anesthesia not necessary to load the radioactive source or while the source is in place. There is no risk of radiation exposure to family or friends after the catheter/needle is removed. HDR brachytherapy is usually combined with EBRT.

Complications — Men who undergo brachytherapy usually experience inflammation and swelling of the prostate gland, which can lead to urinary urgency (needing to void urgently), frequency (needing to void frequently), and burning, and occasionally retention of urine (being unable to empty the bladder completely, which requires temporary use of a catheter). In addition, damage to nearby tissue can cause bowel urgency and frequency, rectal bleeding, and the development of rectal ulcers; these symptoms are rare when brachytherapy is used alone.

The risk of short-term urinary incontinence may be less with brachytherapy than with EBRT as long as patients are selected carefully. Selection criteria from the American Brachytherapy Society suggest that the combination of clinical stage T2a or better, biopsy Gleason score of 6 or less, and PSA level less than 10 ng/mL identifies a group of low-risk patients who are most likely to have excellent long-term oncologic outcomes [3]. Most men who have brachytherapy-related urinary and bowel symptoms improve significantly over time, whereas symptoms may become more severe in men who have EBRT. The risk of ED after brachytherapy is similar to other treatments.

Active surveillance — Some men elect to delay treatment in favor of a program of observation, also called active surveillance (previously called watchful waiting). Active surveillance may be preferred over treatment to avoid treatment-related side effects. With active surveillance, men are carefully monitored, and active treatment (surgery or radiation therapy) can be done if there is evidence that the cancer is progressing. Using this approach, you may be able to avoid or postpone treatment for long periods of time.

Active surveillance can be considered for men who have a normal or minimally abnormal rectal examination who have a high likelihood of low-risk disease (eg, Gleason score less than 6, fewer than three positive biopsy samples out of six that contain less than 50 percent cancerous tissue, a slowly rising PSA (less than 1 ng/mL per year, PSA doubling time greater than 3 years).

Men of any age who have high-risk tumors are strongly discouraged from choosing active surveillance unless there is a serious underlying medical condition that is likely to significantly limit how long he lives.

Monitoring during active surveillance — The National Comprehensive Cancer Network (NCCN) recommends that men who choose active surveillance be monitored by a physician every three to six months.

For men undergoing active surveillance, there are no guidelines that define when to begin treatment. Guidelines from one expert group suggest that a change in risk group (ie, from low-risk to intermediate-risk, (table 1) is a strong indicator that the cancer has progressed and, in most cases, indicates a need for treatment.

OTHER PROSTATE CANCER TREATMENT OPTIONS

Androgen deprivation therapy — Male hormones (androgens, the most common of which is testosterone) fuel the growth of prostate cancer. Treatments that decrease the body's levels of androgens (called androgen deprivation therapy, ADT) decrease the size of prostate cancer. ADT can be done by removing the testicles (called an orchiectomy), or by using medicines that interfere with androgens.

ADT is useful for men who are undergoing RT. Adding ADT to external beam radiation therapy (EBRT) improves outcomes for men with intermediate-risk and high-risk localized prostate cancer, but not those with low-risk disease.

ADT alone versus active surveillance — The use of ADT alone (rather than active surveillance) in men with early stage disease has risks and benefits that are not completely understood.

• There are significant treatment-related side effects with the use of ADT alone, including sexual dysfunction, breast tenderness and enlargement, hot flashes, muscle loss, osteoporotic bone fractures, and accelerated coronary artery disease.
• In addition, there is some evidence that ADT alone actually worsens survival.

For these reasons, the American Urological Association and National Comprehensive Cancer Network recommend against the use of ADT alone as an alternative to active surveillance for men with localized disease.

Side effects of ADT — Side effects of ADT are related to the decreased levels of male hormones, and include:

• Decreased libido (sex drive) and difficulties with erection (erectile dysfunction)
• Hot flashes
• Temporary enlargement of the breasts (called gynecomastia, (see "Patient information: Gynecomastia (breast enlargement in men)".
• Loss of muscle and increase in body fat
• Fatigue
• Thinning and weakening of the bones (called osteoporosis), which can increase the risk of bone fractures. (See "Patient information: Osteoporosis prevention and treatment".)

Cryotherapy — Cryotherapy is a local treatment for prostate cancer in which tumor cells are destroyed by freezing. Cryotherapy is performed in the operating room under anesthesia. After treatment, you go home with a urinary catheter in place for at least three weeks.

The American Urological Association and National Comprehensive Cancer Network do not recommend cryotherapy as a standard treatment option for men with localized prostate cancer.

CLINICAL TRIALS

Progress in treating prostate cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:

       www.cancer.gov/clinical_trials/learning/

       www.cancer.gov/clinical_trials/

       http://clinicaltrials.gov/

SUMMARY: CHOOSING THE RIGHT PROSTATE CANCER TREATMENT

The three standard therapies for men with organ-confined prostate cancer are surgery (radical prostatectomy), radiation therapy (RT), and active surveillance. The "best" treatment for an individual man depends upon several factors.

• The likelihood that the prostate cancer is confined to the prostate gland and therefore, potentially curable.
• The volume and histologic grade (ie, degree of aggressiveness) of the cancer
• A man's age and overall health, including any other medical conditions
• The outcomes and potential side effects associated with the different forms of treatment

The American Urological Association concluded in 2007 that the available data on outcomes and complications of treatments for prostate cancer were insufficient to recommend any one form of treatment over another for any risk category of disease (table 1).

Active surveillance — We believe that men who have the following can consider active surveillance as an initial management option:

• A normal or minimally abnormal rectal examination AND
• A high likelihood of low-risk disease (eg, Gleason score less than 6, fewer than three positive biopsy samples out of six that contain less than 50 percent cancerous tissue, a slowly rising PSA (less than 1 ng/mL per year, PSA doubling time greater than 3 years)

If the cancer begins to progress, radiation therapy or surgery should then be considered. (See 'Active surveillance' above, for a full discussion)

Radiation therapy or surgery — The decision between radiation therapy (RT) and surgery is largely a matter of preference. Surgery and RT offer fairly equivalent survival outcomes, at least for the first 10 years after therapy. Long-term outcomes are probably comparable, although the available data are limited.

Choosing the best treatment depends upon a variety of factors; the most important are the aggressiveness of your cancer, your general health, and how you feel about certain treatment-related side effects.

Low-risk disease — In addition to active surveillance, appropriate treatment options for men with low-risk disease (table 1) include prostatectomy, brachytherapy alone, and external beam radiation therapy.

Intermediate-risk disease — For men with intermediate-risk disease (table 1), external beam radiation therapy or surgery is usually recommended rather than brachytherapy alone.

High-risk disease — For men with high-risk disease, prostatectomy with external beam radiation or external beam radiation therapy plus androgen deprivation therapy are recommended.

Comparison of side effects — The potential risks and complication differ between surgery, EBRT, and brachytherapy. In general:

• In general, urinary control and sexual function are least affected by external beam radiation therapy, more affected by brachytherapy, and most affected by surgery.
• Men who do not have erectile dysfunction prior to therapy who undergo nerve-sparing prostatectomy have a slightly lower risk of urinary and sexual problems compared to men who do not have a nerve-sparing procedure. However, the risks of these problems after nerve-sparing surgery are still greater than those of men who undergo external beam radiation.
• Brachytherapy can cause urinary urgency, frequency, burning, and occasionally retention of urine.
• External beam radiation therapy (EBRT) and brachytherapy cause more bowel urgency and frequency, rectal bleeding, and rectal ulcers than surgery.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Prostate cancer treatment; advanced cancer
Patient information: Prostate cancer diagnosis and staging
Patient information: Sexual problems in men
Patient information: Gynecomastia (breast enlargement in men)
Patient information: Osteoporosis prevention and treatment

Professional Level Information:
Active surveillance for men with early prostate cancer
Brachytherapy for localized prostate cancer
Chemoprevention strategies in prostate cancer
Cryotherapy for prostate cancer
Early stage prostate cancer: Predicting the pathologic extent of disease and clinical outcome
External beam radiation therapy for localized prostate cancer
Follow-up surveillance after treatment for prostate cancer
Interpretation of prostate biopsy
Managing the side effects of androgen deprivation therapy
Measurement of prostate specific antigen
Novel and emerging treatment techniques in prostate cancer
Overview of the clinical presentation, diagnosis, and staging of prostate cancer
Overview of treatment for clinically localized prostate cancer
Radiation therapy for clinically localized prostate cancer: General principles
Radical prostatectomy for localized prostate cancer
Rising serum PSA after radiation therapy for localized prostate cancer: Salvage local therapy
Rising serum PSA after treatment for localized prostate cancer: Systemic therapy

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Cancer Institute

       1-800-4-CANCER
       (www.cancer.gov)

• American Society of Clinical Oncology

      (www.cancer.net/portal/site/patient)

• National Comprehensive Cancer Network

      (www.nccn.com)

• American Cancer Society

       1-800-ACS-2345
      (www.cancer.org)

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• US TOO! International, Inc

      (www.ustoo.org)

Patient Support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Cancer Forum

      (http://cancer.about.com/forum)

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