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•Highlights
•Introduction
•Risk Factors
•Prognosis
•Symptoms
•Diagnosis
•Staging and Grading
•Treatment
•Active Surveillance (Watchf...
•Surgery
•Radiation Therapy
•Hormone Therapy and Chemoth...
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Prostate cancer

Highlights

Prostate Cancer Screening Guidelines

Controversy continues over whether the benefits of prostate specific antigen (PSA) screening outweigh the treatment risks for most men. In general, the current consensus is that there is no "one size fits all" guideline for who should receive prostate cancer screening and at what age. Before deciding to be tested, men need to discuss the pros and cons of screening with their doctors. Men who are at high risk for prostate cancer (family history, African-American) may benefit from early testing. Men with other medical problems may not. Because prostate cancer is very slow growing, doctors generally agree that men over age 75 should not receive routine prostate cancer screening.

Two major studies published in 2009 found that PSA screening saves few if any lives. As a result, the American Cancer Society does not recommend routine PSA testing, although individual men may choose to be tested.

Chemoprevention of Prostate Cancer

In 2009, the American Society of Clinical Oncology (ASCO) and the American Urological Association (AUA) issued a joint guideline recommending consideration of 5-ARI drugs for prostate cancer prevention. Two 5-ARI drugs, finasteride (Proscar, generic) and dutasteride (Avodart) are used for treatment of benign prostate hyperplasia (BPH). Talk to your doctor about whether you should take a 5-ARI drug for reducing prostate cancer risk if you:

There is debate within the medical community on the ASCO/AUA recommendation.

Supplements Do Not Prevent Prostate Cancer

Two major long-term clinical trials have found that vitamin and mineral supplements do not help prevent prostate cancer. In the SELECT trial, researchers found that taking vitamin E or selenium supplements, either alone or in combination, do not prevent prostate cancer development. Similarly, in the Physicians Health Study II trial, vitamin E or vitamin C supplements were ineffective.

Introduction

Prostate cancer is a malignant tumor that arises in the prostate gland. As with any cancer, if it is advanced or left untreated in early stages, it may eventually spread through the blood and lymph fluid to other organs. Fortunately, prostate cancer tends to be slow growing compared to other cancers. As many as 90% of all prostate cancers remain dormant and clinically unimportant for decades. Most older men eventually develop at least microscopic evidence of prostate cancer, but it often grows so slowly that, many men with prostate cancer "die with it, rather than from it."

Prostate gland
The prostate gland is an organ that surrounds the urinary urethra in men. It secretes fluid which mixes with sperm to make semen.

The prostate is a walnut-shaped gland located below the bladder and in front of the rectum. It wraps around the urethra (the tube that carries urine through the penis). The central area of the prostate that wraps around the urethra is called the transition zone. The entire prostate gland is surrounded by a dense, fibrous capsule.

The prostate gland provides the following functions:

  • The glandular cells produce a milky fluid, and during sex the smooth muscles contract and squeeze this fluid into the urethra. Here, it mixes with sperm and other fluids to make semen.
  • The prostate gland also contains an enzyme, called 5 alpha-reductase, that converts testosterone to dihydrotestosterone, another male hormone that has a major impact on the prostate.

The prostate gland undergoes many changes during the course of a man's life. At birth, the prostate is about the size of a pea. It grows only slightly until puberty, when it begins to enlarge rapidly, attaining normal adult size and shape, about that of a walnut, when a man reaches his early 20s. The gland generally remains stable until men reach their mid-40s, when, in most men, the prostate begins to enlarge again through a process of cell multiplication.


Click the icon to see an image of the male reproductive anatomy.

Risk Factors

The major risk factors for prostate cancer are age, family history, and ethnicity.

Prostate cancer occurs almost exclusively in men over age 40 and most often after age 50. Two-thirds of prostate cancers are found in men over age 65. By age 70, about 65% of men have at least microscopic evidence of prostate cancers. Fortunately, the cancer is usually very slow growing and older men with the cancer typically die of something else.

Heredity plays a role in some types of prostate cancers. Men with a family history of the disease have a higher risk of developing prostate cancer. Having one family member with prostate cancer doubles a man's own risk, and having three family members increases risk by 11-fold. A specific gene, named HPC1 (for “hereditary prostate cancer”) is associated with this inherited type of the disease.

Scientists are researching other genetic variations that may increase prostate cancer risk.

Genes
A gene is a short segment of DNA which is interpreted by the body as a plan or template for building a specific protein. Genes reside within long strands of DNA which in turn make up the chromosomes.

African-American men have higher rates of prostate cancer than men of other races. They are also more likely to develop prostate cancer at a younger age and to have more aggressive forms of the disease. However, race alone does fully explain this difference. Prostate cancer is more common in North America and northern Europe, and less common in Africa, Latin America, and Asia. Diet and other factors may play a role. For example, Asians who live in the United States have a higher rate of prostate cancer than those who live in Asia.

Male hormones (androgens), particularly testosterone, may play a role in the development or aggressiveness of prostate cancer. Other types of hormones, such as the growth hormone insulin-like growth factor-1 (IGF-1), may also be associated with some types of prostate cancer.

Researchers are studying whether prostatitis (inflammation of the prostate gland) may be associated with increased prostate cancer risk. They are also examining the possible relationship between prostate cancer and sexually transmitted infections, such as herpes virus and human papillomavirus, but no definite association has yet been found.

Because a Western lifestyle is associated with prostate cancer, so dietary factors have been intensively studied. Results have been inconsistent and inconclusive, however.

Fats. Some studies have found an association between high fat-intake and prostate cancer. In particular, high consumption of red meat and high-fat dairy products has been linked to increased risk for prostate cancer. In contrast, the omega-3 fats in fish may be protective.

Vegetables and Fruits. A diet rich in vegetables, fruits, and legumes appears to protect against prostate cancer. However, it is not clear whether this is due to the nutrients contained in these foods, or the fact that these foods are low in fat. No specific vegetable or fruit has been proven to decrease risk. Lycopene, which is found in tomatoes, has been a target of research interest, but the evidence for its protective benefit is still inconclusive.

Vitamins and Minerals. Major clinical studies have found that vitamin and mineral supplements (vitamin E, vitamin C, vitamin D, and selenium) do not prevent prostate cancer. Nutritious foods that are part of a healthy diet are the best sources for vitamins and minerals. A high intake of calcium has been linked to an increased risk of prostate cancer in some studies.


Click the icon to see an image of the sources of vitamin D.

Click the icon to see an image of the sources of vitamin E.

Finasteride (Proscar, generic) and dutasteride (Avodart) are drugs used to treat benign prostatic hyperplasia (BPH). They block an enzyme that converts testosterone to dehydroepiandrosterone (DHEA), the form of the male hormone that stimulates the prostate. These medications belong to a drug class called 5-alpha-reductase (5-ARI) inhibitors.

In 2009, the American Society of Clinical Oncology (ASCO) and the American Urological Association (AUA) issued a joint guideline recommending that doctors discuss the pros and cons of the use of 5-ARIs for prostate cancer prevention with men who:

ASCO/AUA also recommended that patients who already take finasteride or dutasteride for controlling urinary symptoms of BPH should talk with their doctors about continuing to take the drug for prostate cancer prevention.

The guideline is the first to recommend drug therapy for preventing prostate cancer. It was based on results of a large 7-year clinical trial that showed that finasteride reduced the overall relative risk of developing prostate cancer by about 25%. However, in this study, a few more men who took finasteride developed a high-grade aggressive form of prostate cancer than the men who did not take finasteride. More recent studies have suggested that 5-ARI drugs may not increase the risk of developing aggressive cancer. It is still unclear if finasteride is an appropriate preventive approach, and not all doctors agree with the ASCO/AUA guideline.

Finasteride and dutasteride may cause reduced sexual drive and problems with erection during the first 1 - 2 years of use. It is not yet known what the long-term effects of 5-ARIs are if they are taken for longer than 7 years.

Prognosis

Prostate cancer is the most common male cancer in the U.S. Only lung cancer causes more cancer deaths in American men. The lifetime probability of developing prostate cancer is about 16%. Each year, nearly 200,000 men in the United States are diagnosed with prostate cancer, and about 27,000 die from the disease.

A survival rate indicates the percentage of patients who live a specific number of years after the cancer is diagnosed. For prostate cancer, the 10-year survival rate is about 93% and the 15-year survival rate is about 77%. After 15 years, survival rates stabilize. Research indicates that men who are diagnosed with low-grade prostate cancers have a minimal risk of dying from prostate cancer up to 20 years after diagnosis. However, men diagnosed with more severe forms of prostate cancer have a higher risk of dying within 10 years.

Prostate cancer
Treatment of prostate cancer varies depending on the stage of the cancer and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.

Because so many prostate tumors are low-grade and slow growing, survival rates are excellent when prostate cancer is detected in its early stages.


Click the icon to see an image of the pelvic lymph nodes.

Locally Advanced. If the disease is at the locally-advanced stage, in which it has spread beyond the prostate but only to nearby regions, it is more difficult to cure, but survival rates can be prolonged for years in many men. (When cancer has metastasized to the pelvic lymph nodes, the outlook is worse than if it has spread to other areas.)

Metastasized Cancer. If prostate cancer has spread to distant organs (metastasized), average survival time is 1 - 3 years, but some of these patients may live much longer.

If cancer recurs after initial treatment for early-stage tumors, it is still potentially curable if it is contained within the prostate, although in most cases the cancer has spread. Hormone treatments for such recurring cancers can often prolong survival for years, although the cancer almost always returns again.

Symptoms

Prostate cancer usually causes no symptoms in the early stages. As the malignancy spreads, it may constrict the urethra and cause urinary problems.

Male urinary system
Urine flows from the kidney through the ureters into the urinary bladder where it is temporarily stored. As the bladder becomes distended with urine, nerve impulses from the bladder signal the brain that it is full, giving the individual the urge to void. By voluntarily relaxing the sphincter muscle around the urethra, the bladder can be emptied of urine. Urine then flows out through the urethra.

Later-stage urinary symptoms typically include:

Significant pain in one or more bones may indicate the occurrence of metastases (spread of disease). This chronic pain occurs most often in the spine and sometimes flares in the pelvis, the lower back, the hips, or the bones of the upper legs. It may be accompanied by significant unexplained weight loss and fatigue.

Benign Prostatic Hyperplasia (BPH). BPH is a urinary condition that can develop into an enlarged prostate, which puts pressure on the urethra and causes urinary problems. BPH is not a cancerous or precancerous condition, but its symptoms can mimic late-stage prostate cancer. [For more information, see In-Depth Report #71: Benign prostatic hyperplasia.]

BPH
Benign prostatic hypertrophy (BPH) is a non-cancerous enlargement of the prostate gland, commonly found in men over the age of 50.
Enlarged prostate gland

Click the icon to see an animation about benign prostatic hypertrophy.

Prostatitis. Prostatitis is an inflammation of the prostate, often caused by bacterial infections. Symptoms include urgency, frequency, and pain in urination, sometimes accompanied by fever or blood in the urine.

Diagnosis

There is great uncertainty and controversy over whether the benefits of regular screening for prostate cancer outweigh the risks for most men. Prostate cancer is often slow growing. Doctors cannot yet determine which early-stage tumors pose a risk of being aggressive and need treatment, and which tumors should be left alone. The concern is that routine screening for early detection of tumors may lead to invasive and unnecessary treatment.

In general, the current consensus is that there is no “one size fits all” guideline for who should receive prostate cancer screening and at what age. Before deciding to be tested, men need to discuss the pros and cons of screening with their doctors.

Candidates for Annual Screening. The best age to start annual screening is under debate. Major medical organizations generally recommend that:

Two standard tests are used for early detection of prostate cancer:

Digital rectal exam
Prostate cancer is the most common cancer in men in the United States. Prostate cancer forms in the prostate gland, and can sometimes be felt on digital rectal examination. This is one of the purposes of the digital rectal exam.

PSA Test Limitations. Prostate specific antigen (PSA) is a protein produced in the prostate gland that keeps semen in liquid form. Prostate cancer cells appear to produce this protein in elevated quantities. Measuring PSA levels increases the chance for detecting the presence of cancer when it is microscopic. There are many unresolved questions surrounding PSA testing. The test is not accurate enough to either rule out or confirm the presence of cancer. PSA levels can be increased by various factors other than prostate cancer, including benign prostatic hyperplasia, prostatitis, advanced age, and ejaculation within 48 hours of the test. Relying too much on the test can lead to unnecessary biopsies. Not relying on it enough may miss cancers.

PSA screening may result in the detection of some possible cancers that would never have bothered the patient and would never have posed a threat to his life. Two major studies published in 2009 found that PSA screening saves few if any lives. As a result, the American Cancer Society does not recommend routine PSA testing, although individual men may choose to be tested.


Click the icon to see an image of a PSA blood test.

Biopsy. If cancer is suspected, the doctor will order a biopsy. Only a biopsy, in which a tiny sample of prostate tissue is surgically removed, can actually confirm a diagnosis of prostate cancer. A biopsy is usually performed to confirm or rule out cancer based on a combination of PSA test levels, findings on the DRE, family history, and patient’s age and ethnicity. If a biopsy gives a negative result but the doctor still suspects cancer, repeat biopsies may be performed.

An ultrasound procedure called transrectal ultrasonography (TRUS) may be used to help the doctor see where to take the needle biopsy. Ultrasound is not effective as a diagnostic tool by itself because it cannot differentiate very well between benign inflammations and cancer.

PSA Levels and Velocity. Once cancer is diagnosed, PSA levels may help to determine its extent. If PSA levels are lower than 20 ng/mL, it is likely that the cancer has not spread to distant sites. PSA levels over 40 ng/mL are a strong indicator that cancer has metastasized (spread throughout the body). PSA levels are also monitored after treatments begin. Changes in the level can show if a treatment is working or if the cancer has come back.

Doctors also monitor how quickly PSA levels rise over time. This rate is called PSA velocity (PSAV). The PSAV may help determine when treatment should begin and which treatment should be used. A high rate of PSAV is considered to be 2 ng/mL a year. Recent research suggests that men with early-stage prostate cancer who have a slow PSAV are more likely to live longer than men with rapidly rising PSA levels.

Test for Metastasis. If the biopsy indicates cancer, the doctor will order other tests to determine whether or how far the cancer has spread:


Click the icon to see an image of a CT scan.

Click the icon to see an image of a MRI.

Staging and Grading

A pathologist will read the biopsy report and assign a grade to the tumor cells. The Gleason system classifies and scores the cancers cells based on their microscopic appearance. Based on the grade, PSA test, digital rectal exam, and possibly imaging tests, the doctor stages the cancer. Staging refers to how far the cancer has spread. The stage and grade of cancer can help the doctor advise on treatment options.

A tumor's stage is an indication of how far it has spread from its original site. Cancers are staged according to whether they are still localized (still within the prostate gland) or have spread beyond the original site. The current prostate cancer staging system is the TNM system.

The TNM system refers to clinical tumor stages as:

T followed by numbers 0 through 4 refers to the size and extent of the tumor itself.

T1

The tumor cannot be felt or seen using imaging techniques.

T1a. Cancer cells are incidentally found in 5% or less of tissue samples from prostate surgery unrelated to cancer.

T1b. Cancer cells found in more than 5% of samples.

T1c. Cancer cells identified by needle biopsy, which is performed because of high PSA levels.

T2

The cancer is confined to the prostate but can be felt as a small well-defined nodule.

T2a. Tumors are in half a prostate lobe.

T2b. Tumors are in more than half a lobe.

T2c. Tumors in both lobes.

T3

The tumor extends through the prostate capsule.

T4

The tumor is fixed to or invades adjacent structures.

N followed by 0 through 3 refers to whether the cancer has reached the regional lymph nodes, which are located next to the prostate in the pelvic region.

N0

Regional lymph nodes are still cancer-free.

N1

A small tumor is in a single pelvic node.

N2

A medium-size tumor is in one node, or small tumors are in several nodes.

N3

A large tumor is in one or more nodes.

M stages refer to metastasis (tumors developing outside the prostate).

M0

Metastasis has not occurred (cancer has not spread beyond the regional lymph nodes).

M1a

Cancer has spread to lymph nodes beyond the regional lymph nodes.

M1b

Cancer has invaded the bones.

M1c

Cancer has spread to other sites.

Tumors are assigned scores according to a scale known as the Gleason system, which measure how well or how poorly organized the cancer cells are under the microscope. The first step is to grade the tumors:

Two-thirds of prostate cancers have a mix of tumor grades. To determine a prognosis, two numbers are assigned, representing the dominant grade and then the minor grade. The cancer is then "scored" by adding the dominant grade plus the minor grade. For example, a tumor with a dominant grade of 3 and a minor grade of 4 are given a Gleason score of 7. The following scores are often used to suggest how well or poorly the tumor is differentiated. The higher the score, the more severe the break-down of their cellular structure and the more likely they are to spread aggressively:

Treatment

Treatment choices are generally based on the patient's age, the stage and grade of the cancer, overall health status, and the patient's personal preferences for the risks and benefits of each therapy.

Patients should be aware that doctors may be biased to prefer a specific treatment depending on their specialty, with urologists tending to recommend surgery and radiation oncologists recommending radiation therapy. It is always wise to seek a second opinion. Delaying treatment, while having the cancer monitored for signs of progression, is also an acceptable option.

Stages indicate the extent of the cancer:

Depending on the cancer stage and other factors, patients have four main treatment options:

The U.S. National Cancer Institute recommends the following treatment options by cancer stage:

Tumors: T1a, N0, M0, G1, Stage A

Prostatectomy - series

Click the icon to see an illustrated series detailing prostatectomy surgery.

Tumors: T1a - c, N0, M0, any G, Stage A2, B1, or B2

Overview of Treatment Options for Localized Prostate Cancer. To date, neither treatment nor active surveillance has emerged with a definitive survival advantage for localized prostate cancer. However, several recent studies have suggested that treatment provides a survival advantage over watchful waiting for some men with early-stage prostate cancer.

Recent guidelines recommend that patients with localized cancer should be classified as low, intermediate, or high risk. Doctors determine the risk category by using criteria such as PSA tests, tumor aggressiveness, and the clinical stage of the tumor. Based on these risk groups, evidence indicates that:

Tumors: T3, N0, M0, any G, Stage C

TURP - series

Click the icon to see an illustrated series detailing transurethral resection of the prostate.

Tumors: Any T, any N, any M, any G, Stage D1 - D2

If prostate cancer has been eliminated after initial treatment, PSA levels should drop after surgery. After radiation, they may not drop as far because some of the prostate gland may remain. A sudden rise or persistently elevated PSA levels after treatment are often indications that prostate cancer persists.

It is common for PSA levels to temporarily rise following radiation seed implantation without signaling cancer recurrence. Rising PSA levels do not necessarily mean that the cancer has spread or even that clinical cancer will recur during a man's lifetime.

Treatment options for recurrent cancer depend on various factors, including prior treatment, site of recurrence, coexistent illnesses, and individual patient considerations.

Prostate cancer treatments can cause distressing side effects by impairing sexual function (erectile dysfunction), urination (incontinence or difficulty urinating), bowel function (incontinence), and energy levels (fatigue). A man must weigh his own emotional responses to the possibility of these side effects versus the possible stress of active surveillance.

Side effects vary among patients and it is difficult to predict how an individual patient will respond. In general, the side effects most likely to occur by treatment modality are:

Active Surveillance (Watchful Waiting)

Watchful waiting involves lifestyle change and careful monitoring for cancer progression. Over the last several years, watchful waiting has evolved into a strategy called “active surveillance,” or “delayed surgical intervention.” With this approach, patients have a digital rectal exam and PSA blood test every 6 - 12 months. If test results indicate cancer progression, doctor and patient consider treatment options (surgery, radiation, or drugs). Patients should exercise and eat healthy foods. Patients should report symptoms such as weight loss, pain, urinary problems, fatigue, or impotence to their doctors.

Candidates. Active surveillance may be most appropriate for the following patients:

Some doctors think that because prostate cancer grows so slowly, it is likely that older men will die from causes unrelated to the cancer. There is therefore little potential benefit from surgery or radiation, with both posing a risk for erectile dysfunction and incontinence. The choice is a difficult one. It is important that patients find a doctor who can provide them with all the necessary information so that they can make an informed decision.

Surgery

In men whose cancer is confined to the prostate, surgical resection (radical prostatectomy) offers the potential for cure. Cure rates from initial surgery in men with localized cancer are about 90%, depending on tumor stage, tumor grade, PSA levels, and overall health of the patient. Research suggests that surgery provides long-term cancer control. Most patients can consider themselves disease-free if their PSA levels remain undetectable 10 years after surgery.

Radical prostatectomy is the surgical removal of the entire prostate gland along with the seminal vesicles (the vessels that carry semen) and surrounding tissue. The surgeon may also remove the pelvic lymph nodes. The incision can be made in one of the following regions:

The gland and other structures are then removed. The operation lasts 2 - 4 hours.

Laparoscopic Prostatectomy. Less invasive surgical techniques using laparoscopy have been developed for radical prostatectomy. These techniques use smaller incisions and allow faster recovery, but they require special surgical training. Laparoscopic surgery may also be done using a robotic system, which involves the surgeon directing a robotic arm through a computer monitor. Not every hospital can do robotic-assisted laparoscopic prostatectomy and these procedures are difficult to perform.

Prostatectomy - series

Click the icon to see an illustrated series detailing prostatectomy surgery.

Nerve-Sparing Techniques. In the retropubic approach, the surgeon will attempt to spare the nerves that control erection:

Nerve-sparing techniques can improve quality of life, by decreasing the occurrence of incontinence and erectile dysfunction. In cases where the tumor lies too closely to the nerve, nerve-sparing techniques may not be possible.

Convalescence. Patients remain hospitalized for about 3 days after an open procedure or 2 days after less invasive procedure. Full recovery at home takes about 3 - 5 weeks. A temporary catheter used to pass urine is kept in place when the patient is sent home and is usually removed about 3 weeks after the open operation or 1 week after their robotic procedure. In general, younger patients with early-stage cancers recover fastest and experience the fewest side effects.

The main complications from radical prostatectomy are urinary incontinence and erectile dysfunction. Other complications include the usual risks of any surgery, such as blood clots, heart problems, infection, and bleeding.

Urinary Incontinence. Urinary incontinence is a common complication. When the urinary catheter is first removed following surgery, nearly all patients lack control of urinary function and will leak urine for at least a few days and sometimes for months. Normal urinary function usually returns within about 18 months. A percentage of men will continue to have small amounts of leakage with heavier exertion or possibly sexual activity.


Click the icon to see an image of catheterization.

If incontinence persists beyond a year, patients may require drug therapy or surgery. [For more information, see In-Depth Report #50: Urinary incontinence.]

Erectile Dysfunction. Erectile dysfunction after radical prostatectomy is caused by nerves that were damaged or removed during the surgery. Virtually all men will have problems with erectile dysfunction after surgery. It can take up to one to two years to recover erectile function after surgery. Because seminal glands are removed along with the prostate gland during surgery, men who regain sexual function will not produce semen during orgasm (“dry ejaculation”).

With the use of effective nerve-sparing techniques, men who were sexually active before surgery and are involved in an ongoing relationship seem to have a better chance of returned sexual function. Drugs such as sildenafil (Viagra) may help some men regain erectile function. Use of these drugs three times a week accompanied by sexual stimulation is now commonly recommended. Other treatments for erectile dysfunction (alprostadil injections, vaccum devices, penile implants) may also be options. [For more information, see In-Depth Report #15: Erectile dysfunction.]

Radiation Therapy

Radiation therapy may be used as an initial treatment for localized prostate cancer. It may also be used as treatment for cancer that has not been fully removed or has recurred after surgery. In advanced cancer, radiation therapy is used to shrink the size of the tumor and relieve symptoms.

Radiation therapy used to be reserved for older men (over age 70) with locally advanced prostate cancer who had a life expectancy of 15 years or less. However, it is now being used more frequently in younger and healthier men.

The two main radiation treatments for prostate cancer are:

Both treatments have generally equal success rates. In some cases, both techniques may be used in high-risk patients.

In external beam radiation therapy, a doctor focuses a beam of radiation directly on the tumor for 35 3-minute treatments given 5 times a week over 7 weeks. 3-D conformal techniques use computers and a three-dimensional image of the prostate to target the tumor precisely, using high-dose radiation beams. It poses a lower risk for inflammation.

Patients considering external beam radiation should be aware that higher radiation doses may reduce the risk for cancer recurrence and improve survival outcome.

Brachytherapy is a technique that implants radioactive "seeds" directly into the prostate. Implants can be temporary or permanent. Temporary implants are usually accompanied by external beam radiation. This procedure requires more skill than external beam radiation therapy. Even with experienced doctors, the distribution of radioactive seeds may be uneven, increasing the risk for insufficient doses. In addition, in some cases the seeds can migrate through the bloodstream to other parts of the body.

It is common for PSA levels to temporarily rise, or "bounce," following seed implantation. This effect is not necessarily a sign of cancer recurrence.

Brachytherapy is mainly used for men who have early stage prostate cancer that is relatively slow growing. It is also used in combination with external beam radiation to treat intermediate-risk localized prostate cancer. Poorer candidates for brachytherapy include men who have had transurethral resection of the prostate (TURP) and patients with advanced cancer, high-grade tumors, or very enlarged prostate glands.

Fatigue is a common side effect for several months following radiation therapy. Other complications include:

Gastrointestinal and Bowel Complications. Complications in the gastrointestinal tract are common. Short-term effects include nausea and loss of appetite. Diarrhea is a very common side effect and can last for the duration of therapy. It is usually treated with Lomotil. It usually goes away eventually, but a few patients have diarrhea flare-ups for years afterwards.

Urinary Problems. Many patients experience a need for frequent urination shortly after radiation therapy, and urgency persists longterm for about some patients.

Erectile Dysfunction. Unlike surgery, erectile dysfunction does not usually occur immediately following radiation therapy. However, the risk for this complication increases after a year or more. External beam radiation may be better at preserving sexual function than brachytherapy. Drug therapies for erectile dysfunction may help. [For more information, see In-Depth Report #15: Erectile dysfunction.]

Radiation may help select patients who still show detectable levels of PSA after surgery (generally 2 ng/mL or less). It may even be useful years after surgery if PSA levels rise.

Depending on timing, radiation after treatment failure is referred to as either:

Cryosurgery is an alternative to standard prostatectomy for men with localized prostate cancer who do not want or who are not appropriate candidates for radical prostatectomy. It is also an alternative to radiation therapy. The goal of cryosurgery is destruction of the entire prostate gland and possibly surrounding tissue. Steel probes are inserted through the skin between the anus and the rectum and into the prostate. Liquid nitrogen is pumped through the probes to freeze all prostate cells, both healthy and cancerous. For success, cryosurgery requires a uniformly frozen area. The dead cells are absorbed and eliminated by the body.

Cryosurgery is typically a 2-hour outpatient procedure, although some patients may need to stay in the hospital overnight. Cryosurgery may also be used as a salvage procedure for patients who have undergone radiation therapy and have had cancer recurrence detected early.

Nearly all patients experience erectile dysfunction after cryosurgery, and urinary incontinence is also common. Other complications of cryosurgery include urinary retention, swelling, and fistula formation. Incontinence and fistulas tend to occur more when cryosurgery is used as a salvage procedure than when it is used as a primary procedure.

This therapy is still considered experimental by some doctors, and there are no long-term data to compare its effectiveness with standard prostatectomy. For this reason, cryosurgery is generally not considered as a first-line initial treatment.

Hormone Therapy and Chemotherapy

Male hormones (called androgens), particularly testosterone and dihydrotestosterone, determine male secondary sex characteristics and stimulate prostate cell growth. When prostate cells, both healthy and cancerous, are deprived of androgens, they no longer proliferate and eventually die.

Androgen deprivation therapy (also called androgen suppression therapy or hormone therapy) uses drugs or surgery to suppress or block male hormones, particularly testosterone and dihydrotestosterone, that stimulate the growth of prostate cells. Androgen deprivation therapy is not a cure for prostate cancer, but it can help control symptoms and disease progression.

Androgen deprivation therapy is used for advanced and metastatic cancer and may be used if treatment for localized prostate cancer has failed and cancer recurs (as indicated by rising PSA levels).

There has been some debate about when to start androgen deprivation therapy. In 2007, the American Society of Clinical Oncology (ASCO) published clinical guidelines for androgen deprivation therapy in patients with recurrent, progressive, or advanced prostate cancer. The guidelines recommend that hormone therapy should, in general, be delayed until patients begin to experience symptoms from their cancer. However, when therapy is deferred, patients should regularly visit their doctors every 3 - 6 months for careful monitoring of their condition.

ASCO recommends either removal of both testicles (bilateral orchiectomy) or injections with luteinizing hormone-releasing hormone (LHRH) as initial androgen deprivation treatments. Combining antiandrogen drug therapy with orchiectomy or LHRH may also be considered.

When prescribing hormone therapy drugs, some doctors recommend periodically stopping and restarting treatment (intermittent therapy). This approach may help men avoid the loss of sexual function. More research needs to be conducted to determine the effectiveness of intermittent therapy.

Orchiectomy is the surgical removal of the testicles (surgical castration). It is the single most effective method of reducing androgen hormones, but because it is permanent it is not suitable for intermittent or temporary androgen deprivation. Orchiectomy plus radical prostatectomy may delay progression in patients with cancers that have spread only to the pelvic lymph nodes.

Men who have orchiectomy have reduced sexual function and desire. Patients do not experience a reversal of sex characteristics and the voice does not change. Like all androgen deprivation therapies, orchiectomy increases the risk for osteoporosis.

The primary drugs used for suppressing androgens are called luteinizing hormone-releasing hormones (LHRH) agonists. LHRH drugs block the pituitary gland from producing hormones that stimulate testosterone production. They include leuprolide (Lupron, Leuprogel), goserelin (Zoladex), and buserelin.

Treatment with LHRH agonists produces a testosterone surge in the first week, which may actually intensify symptoms. After this phase, testosterone levels drop to near zero. LHRH agonists can also cause PSA levels to rise temporarily.

Side Effects. Side effects include hot flashes and occasionally nipple and breast tenderness.

Anti-androgens are drugs used to block the effects of testosterone. They are generally used in combination with LHRH agonists or orchiectomy to completely block androgen hormones. This combination approach is called combined androgen blockade (CAB) in the U.S., and maximal androgen blockade (MAB) in Europe.

The main anti-androgen drugs include flutamide (Eulexin, Drogenil), nilutamide (Nilandron), and bicalutamide (Casodex). Diarrhea is the most common side effect.

If patients do not respond to standard hormonal medications, other drugs may be tried. They include estrogen therapy and ketoconazole (Nizoral), an anti-fungal drug that blocks testosterone production.

In 2008, the FDA approved degarelix as a hormonal drug treatment for advanced prostate cancer. Degarelix belongs to a class of drugs called gonadotropin releasing hormone (GnRH) receptor inhibitors. It works by suppressing testosterone and thereby slowing the growth and progression of prostate cancer. Degarelix is given by injection. It is the first new drug approved in several years for treatment of prostate cancer.

Androgen Deprivation Therapy Before or With Radiation. Hormonal drugs combined with radiation therapy may improve survival rates in moderate- or high-risk groups. Patients may need to take these drugs long-term to improve outcomes. Hormonal drugs before radiation (neoadjuvant therapy) may be helpful in shrinking enlarged glands so that brachytherapy (radiation implants) can be used.

Androgen Deprivation Therapy Before or After Surgery. Some studies suggest benefits from using hormone therapy before surgery (neoadjuvant therapy) to reduce the tumor size, but this approach does not appear to increase survival.

Men often experience fatigue, loss of energy, and emotional distress from androgen suppression treatment. Hormonal therapy may significantly impair quality of life, particularly in men who had no symptoms beforehand and whose cancer has not metastasized. Common side effects of androgen suppression drugs include:

In addition, there is growing evidence that androgen deprivation therapy increases the risks for heart attack, stroke, and diabetes.

Prostate cancer that does not respond to hormonal treatment is called hormone-resistant, or hormone-refractory, cancer. Chemotherapy may be used to treat hormone-resistant cancer.

Chemotherapy drugs for prostate cancer include docetaxel (Taxotere), mitoxantrone (Novantrone), estramustine (Emcyt), and various platinum-based drugs, such as carboplatin. These drugs are often combined with other cancer drugs (such as 5-fluorouacil) or corticosteroids (such as prednisone).

Docetaxel-based drug regimens are emerging as the main chemotherapy treatment for hormone-refractory prostate cancer. In 2004, the FDA approved docetaxel injection in combination with prednisone for treatment of patients with hormone-resistant prostate cancer. Patients who received this drug combination survived on average 2.5 months longer than patients who received mitoxantrone and prednisone. Side effects can be serious and may include gastrointestinal problems (nausea, vomiting, or diarrhea), fatigue, low blood cell counts, and increased risk for blood clots.

Researchers are continuing to investigate docetaxel combinations and compare them to other chemotherapy regimens.

Resources

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Review Date: 8/5/2009
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.
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