Prostate cancer
Highlights
Prostate Cancer Screening Guidelines for Older Men
In 2008, the U.S. Preventive Services Task Force (USPSTF) changed its guidelines for prostate-specific antigen (PSA) screening.
- The USPSTF now recommends against routine PSA testing for men ages 75 and older. More studies will be needed to determine if this test is helpful for younger men.
- The new recommendations reflect evidence that the side effects of treatment for this age group outweigh the possible benefits of early diagnosis and treatment.
- Prostate cancer is very slow growing. In older men, it is likely that symptoms may not appear during their lifetimes. Radiation and hormone treatments can cause significant side effects and adversely affect quality of life. Surgery is not usually an appropriate treatment choice for older men.
Hormone Therapy for Older Men
Hormone therapy, also called androgen deprivation therapy, does not improve survival among older men with early prostate cancer when compared with watchful waiting, indicates a 2008 study in the Journal of the American Medical Association. In the study of over 19,000 men with an average age of 77 years, researchers found no survival differences between men who received either hormone drugs or surgical removal of testicles (orchiectomy) and those who received no treatment. Hormone therapy causes impotence and may increase the risks of heart attack, stroke, and diabetes.
Quality of Life After Prostate Cancer Treatments
Many men are concerned about the side effects of prostate cancer treatments. A 2008 study in the New England Journal of Medicine analyzed the differences in quality of life outcomes for surgical removal of the prostate gland (prostatectomy) and radiation therapy. The researchers found that:
- External beam radiation therapy generally provides the best results for recovery of sexual function.
- Nerve-sparing prostatectomy generally produces better sexual function than conventional radical prostatectomy.
- External beam radiation therapy produces better urinary control and sexual function than brachytherapy, but brachytherapy has better results for these side effects than radical prostatectomy.
- Both brachytherapy and external beam radiation generally cause more bowel problems than surgery, although this side effect usually improves after 1 year.
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 can 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. This high incidence of latent or incidental malignancy is unique to the prostate gland. Most older men eventually develop at least microscopic evidence of prostate cancer, but it often grows so slowly that, as one specialist has written, many men with prostate cancer "die with it, rather than from it."
The Prostate GlandDescription of the Prostate Gland The prostate gland is located between the bladder and the rectum and wraps around the urethra (the tube that carries urine through the penis). It is basically composed of three different cell types:
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. Functions of the Prostate Gland The prostate gland provides the following functions:
Changes During the Lifespan 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.
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, about 187,000 men in the United States are diagnosed with prostate cancer, and about 29,000 die from the disease. According to the American Cancer Society, 5-year survival rates for all stages of prostate cancer have increased during the past 20 years from 67% to nearly 100%.
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.
Prognosis for Early Stage Disease
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.
Prognosis in Late Stage Disease
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 longer or die of other causes.
Prognosis after Recurrence
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.
Risk Factors and Prevention
The major risk factors for prostate cancer include age, family history, and ethnicity.
Age
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. It is estimated that by age 70, about 65% of men have at least microscopic evidence of prostate cancers. Fortunately, the cancer is often very slow growing and older men with the cancer nearly always die of something else.
Family History and Genetic Factors
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.
Ethnicity
African-American men have the world's highest risk for prostate cancer, more than 50% higher than the risk for Caucasian males. The disease is also more lethal among African-Americans. Men who live in Asia have lower risks for prostate cancer, but their risk increases if they move to North America. This indicates that there may be unknown environmental or dietary factors that can alter a man's underlying genetic risk of developing this disease.
Socioeconomic Issues. The higher mortality rates in African-American men may be partly due to socioeconomic factors, such as lack of insurance, irregular screening and a late diagnosis, and unequal access to health care.
Dietary Factors. Dietary factors may play some small role in the higher risk in African-American men. This is suggested by the fact that prostate cancer is rare in many parts of Africa.
Biologic Factors. Evidence suggests that African-American and Asian men have certain genetic factors that may affect male hormones differently and may help account in part for the higher risk in the first group and the lower risk in the second.
Higher PSA Levels. African-American men also tend to have higher PSA levels than Caucasians. They are overdiagnosed with prostate cancer by 37% compared to 15% in Caucasians using PSA screening tests.
Other Factors Possibly Associated with Prostate Cancer
Hormones. 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.
Infection and Inflammation. 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. Some research indicates that men with a hereditary form of prostate cancer may be more susceptible to viral triggers.
Obesity. Although obesity does not appear to be linked to most cases of prostate cancer, it may increase the risk for more aggressive forms of the disease. Obesity may also make prostate cancer more difficult to diagnose.
Vasectomy. Because testosterone levels remain higher for a longer period in men who had vasectomy, researchers have theorized that such men have a greater chance for developing the cancer. While some older studies have suggested a higher risk with vasectomy, recent studies have reported no higher danger. [For more information, see In-Depth Report #37: Vasectomy.]
Click the icon to see an illustrated series detailing a vasectomy.
Click the icon to see an animation on vasectomy.
Dietary Factors
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. Some research also suggests that a low-fat diet may protect against prostate cancer.
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 Mineral Supplements
There is some evidence that certain vitamin and mineral supplements (such as vitamin D, vitamin E and selenium) can protect against prostate cancer, and also some evidence that excessive use of supplements may increase risk. However, using multivitamin supplements occasionally or once a day does not appear to increase prostate cancer risk. Still, nutritious foods that are part of a healthy diet are the best sources for vitamins and minerals.
Many studies indicate that vitamin D may help protect against prostate cancer. Vitamin E has also been extensively studied, but has not yet been proven to affect risk. The U.S. National Cancer Institute is conducting a large-scale clinical trial to investigate whether the mineral selenium, vitamin E, or a combination of these two dietary supplements can help prevent prostate cancer.
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.
Alcohol
Alcohol consumption does not appear to be associated with increased prostate cancer risk.
Exercise
Some, but not all, studies indicate regular physical activity may help reduce the risk of prostate cancer and slow the progression of the disease. The beneficial effects of exercise may be particularly important for older men.
Sexual Activity
Frequent ejaculations from masturbation or sexual activity have been associated with a lower risk for prostate cancer. However, unsafe sexual activity increases the risk for sexually transmitted disease, which may in turn increase the risk for prostate cancer.
Finasteride (Proscar)
Finasteride (Proscar) is a drug used to shrink the prostate in men with benign prostatic hyperplasia (BPH). It blocks an enzyme that converts testosterone to dehydroepiandrosterone (DHEA), the form of the male hormone that stimulates the prostate. Researchers are investigating whether finasteride may help prevent prostate cancer. There is some evidence that finasteride may decrease the overall risk of prostate cancer, but increase the risk for higher-grade and more aggressive forms of the disease. It is still unclear if finasteride is an appropriate preventive approach.
Symptoms
Prostate cancer usually causes no symptoms in the early stages. As the malignancy spreads, it may constrict the urethra and cause urinary problems.
Later Stage Urinary Symptoms
Later-stage urinary symptoms typically include:
- Weak urinary stream
- Inability to urinate
- Blood in the urine
- Interruption of urinary stream (stopping and starting)
- Frequent urination (especially at night)
- Pain or burning during urination
Late Stage General Symptoms
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 weight loss.
Conditions with Similar Symptoms
Benign Prostatic Hyperplasia (BPH)
In up to half of men in their 40s, the prostate begins to enlarge through a process of cell multiplication called benign prostatic hyperplasia (BPH). The symptoms of BPH can mirror late-stage prostate cancer because the enlarging inner portion of the prostate puts pressure on the urethra, which can potentially cause urinary problems. About 80% of men eventually develop enlarged prostates, but only some experience significant symptoms. BPH is a normal condition and is not life threatening. [For more information, see In-Depth Report #71: Benign prostatic hyperplasia.]
Relationship to Prostate Cancer. Because the prostate enlargement in BPH is affected by testosterone, many men are concerned that it may be related to prostate cancer. Fortunately, current evidence indicates that it has no effect one way or the other. The two conditions develop in different parts of the prostate. BPH occurs in the inner zone of the prostate, while cancer tends to develop in the outer area. A 10-year study found no higher risk for prostate cancer in men with BPH.
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.
Screening and Diagnosis
There is great uncertainty over whether regular screening has major benefits for most men. The most recent guidelines from the U.S. Preventive Services Task Force report that there is no conclusive evidence that routine prostate screening saves lives. Indeed, it may lead to invasive testing, and to treatments for many men who, considering the slow growth of the cancer, might derive no benefits from them. It is a difficult subject, and men must discuss all aspects carefully with their doctor.
Doctors should inform men of the uncertainty in accuracy of prostate cancer tests so that patients understand the relative risks and benefits of screening.
Candidates for Annual Screening. The best age to start annual screening is under debate. Major medical organizations generally recommend that:
- Men ages 50 - 70 should be offered annual screening. (Some experts believe that men whose PSA levels are under 1.0 and possibly under 2.0 may safely be screened only every 2 years thereafter.)
- Men with a family history of prostate cancer and all African-American men should consider annual screening at about age 45.
- PSA testing is generally not recommended for men over age 75. Because of shortened lifespan, responding to abnormal PSA results in this age group may lead to overly aggressive treatment.
Scientists are working on developing more accurate tests that, hopefully, will one day replace the PSA test. A promising experimental test in development measures a protein called early prostate cancer antigen-2 (EPCA-2). Researchers hope that this test may eventually provide better diagnoses of prostate cancer, and help prevent men from receiving unnecessary biopsies.
Standard Screening Tests for Early Detection
Two standard tests are used for early detection of prostate cancer:
- PSA test. The PSA blood test measures the level of a protein called prostate-specific antigen. It is able to detect early prostate cancer, although it has limitations.
- Digital rectal examination (DRE). The DRE is a physical examination. The doctor inserts a gloved and lubricated finger into the patient's rectum and feels the prostate for bumps or other abnormalities.
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 completely rule out or confirm the presence of cancer. Relying too much on the test may lead to unnecessary biopsies. Not relying on it enough may miss cancers. It is still unclear if PSA testing is actually saving lives.
Click the icon to see an image of a PSA blood test.
Factors Affecting PSA Levels. A number of factors and noncancerous conditions can influence PSA levels:
- Ethnicity. Normal levels in Caucasian males may be different from those for African-American or Asian men.
- Age. PSA levels tend to rise naturally with age, so an elevated level in a man who is 70 may be less serious than the same level in a younger man. Some doctors believe that men older than 65 who have low PSA levels are at such low risk for prostate cancer that they may be able to forgo further testing.
- Benign Prostatic Hyperplasia (BPH) and Its Treatments. Between 25 - 56% of patients with BPH have elevated PSA levels. Certain treatments for this condition can also elevate PSA.
- Prostatitis. About half of men with elevated PSA levels but no signs of cancer on biopsy have signs of prostatitis as indicated by urine and prostate secretion tests. (Prostatitis simply means inflammation in the prostate. Inflammation is usually due to bacterial infection, but it can also be caused by nonbacterial factors.)
- Other Noncancerous Conditions. Other noncancerous conditions that can increase PSA levels include surgical procedures or drug treatments for BPH, acute urinary retention, digital rectal examinations, and prostate biopsies themselves.
- Ejaculation. Ejaculation within 48 hours before testing can raise PSA levels.
Even with its limitation, the PSA test has increased the number of detectable early-stage, and therefore treatable, cancers. Because of the slow-growing nature of prostate cancer, however, it is not known whether all of these very early cancers will result in significant or life-threatening disease. It is possible that PSA screening could 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.
PSA Test Variations
To improve the accuracy of the PSA tests, particularly when PSA levels have risen to an intermediate range of between 4 - 10 ng/mL, researchers are developing methods for measuring other factors. To date, no test has emerged as clearly superior to the PSA test.
Free PSA Test. One particular type of test is called the free PSA test. A small amount of prostate specific antigen leaks out of the prostate into the bloodstream. There, PSA can circulate without binding to other proteins and is referred to as free PSA. It can also form chemical combinations with other proteins. If cancer is present, PSA is more likely to be bound, and so there is less free PSA in circulation. The free PSA blood test, then, is a ratio of free PSA to the total PSA (free PSA plus chemically bound PSA).
The following results are used to determine if an elevated PSA level could mean cancer:
- A free-to-total PSA ratio of 20% or lower, plus total PSA levels of 4 - 10 ng/mL, are suggestive of prostate cancer. (Some experts use 25% as a cut-off, but studies suggest that using this cut-off would miss cancers in many African-American and older men.)
- A free-to-total PSA level of more than 20% plus normal or even moderately elevated total PSA tend to indicate the presence of other, benign conditions, such as benign prostatic hyperplasia (but it still does not rule out cancer).
Not all studies support the free PSA tests advantages compared to measuring total PSA alone, and to date there is no consensus among doctors for when it should be used.
Ultrasound (Transrectal Ultrasonography)
An ultrasound procedure called transrectal ultrasonography (TRUS) provides a visual image of the prostate and is used if the DRE indicates the presence of cancer. Ultrasound is not effective as a diagnostic tool by itself because it cannot differentiate very well between benign inflammations and cancer, but the procedure may help to confirm an uncertain preliminary diagnosis and is useful as a guide for needle biopsies. Ultrasound enhancements, such as Doppler imaging or computer modeling techniques called artificial neural networks (ANN), may increase the accuracy of TRUS.
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 after screening tests that report:
- PSA level of 4.0 ng/mL or higher. Some evidence indicates that men with an initial test showing PSA levels above 4.0 should take a second PSA test several weeks afterward before having a biopsy, since many non-malignant factors can increase PSA levels.
- Abnormal DRE
Men with abnormal results from both tests have about a 60% chance of prostate cancer. The chances for cancer if only one test is abnormal are considerably lower. To further complicate matters, biopsies themselves may miss very small cancers detected by PSA levels alone. Because a biopsy can miss very small cancer cells, sometimes three or even more biopsies are recommended if cancer is still suspected after negative results.
If prostate cancer appears certain, doctors may also perform a lymph node biopsy to see if the cancer has spread.
Tests to Determine Severity of Cancer
PSA Levels and Velocity
Once cancer is diagnosed, PSA levels may help to determine its extent. If PSA levels are fewer than 20 ng/mL, it is possible 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.
Tests for Metastasis
If the biopsy indicates cancer, the doctor will order other tests to determine whether or how far the cancer has spread.
Bone Scans and X-Rays. Bone scans and x-rays may reveal whether the cancer has invaded the bones. To perform a bone scan, doctors inject low doses of a radioactive substance into the patient's vein, which accumulates in bones that have been damaged by cancer. A scanner then reveals how much of the radioactive material has accumulated. Arthritis and infections may also produce positive scans. Patients with PSA levels below 20 ng/mL are unlikely to have scans that show cancer in the bone.
Computed Tomography and Magnetic Resonance Imaging. Computed tomography (CT) or magnetic resonance imaging (MRI) scans can further pinpoint the location of cancer that has spread beyond the prostate. Advanced MRI techniques are showing promise for staging and planning treatments.
Click the icon to see an image of a CT scan.
Click the icon to see an image of a MRI.
Staging and Grading
Staging and Grading
Doctors are continually searching for methods to determine how aggressive a given prostate cancer is in an individual patient so they can choose the best treatments. As an aid, experts have devised different classification systems that help assess the properties of the cancer. These systems include staging and grading the tumors and measuring PSA levels. In general, the higher the stage, grade, and PSA numbers, the more severe the condition and the more aggressive the treatment. Current classifications systems have significant limitations in guiding treatment choices. Newer tests, markers, and imaging techniques may eventually improve the accuracy of staging categories.
Staging Systems
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. Two prostate cancer staging systems are commonly used: the TNM system and the Jewett system. To avoid confusion, this report discusses uses only the TNM system. The TNM system is explained in detail, and the Jewett system is explained in reference to the TNM system.
TNM Staging System
The TNM system refers to clinical tumor stages as:
- T for tumor
- N for regional lymph nodes
- M for metastasis (tumors developing outside the prostate)
T Stages
T followed by numbers 0 through 4 refers to the size and extent of the tumor itself.
Stage, T1 - T4 | Description |
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 Stages
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.
Stage, N0 - N3 | Description |
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
M stages refer to metastasis (tumors developing outside the prostate).
Stage | Description |
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. |
Jewett Staging System
The stages in the Jewett system are roughly equivalent to the stages in the TNM system as follows:
Jewett Stage | TNM Stages |
A | T1 |
B | T2 |
C | T3, T4 |
D | N1, N2, N3, M1 |
The Gleason Grading System
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:
- Grade 1: Single, well-packed tumors
- Grade 2: Single, more loosely arranged and less uniform tumors
- Grade 3: Single tumors of different sizes and patterns, with cellular breakdown becoming increasingly worse
- Grade 4: Irregular tumor masses, fused together; may show clear cells
- Grade 5: The tumors have broken down and cellular structure has markedly deteriorated
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:
- Score 2 - 4: Well-differentiated. Indicates about a 95% chance for surviving 15 years without aggressive treatment.
- Score 5 - 6: Moderately well differentiated. Slightly lower chance of survival that decreases with time.
- Score 7 - 10: Moderately poorly to poorly differentiated, with 15-year survival rates of 15 - 40%.
Treatment Options by Staging and Grading
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.
Stages indicate the extent of the cancer:
- Stage I and stage II cancer are considered early stage. The cancer is localized and has not spread outside the prostate gland.
- Stage III, locally advanced cancer, means that the cancer has spread into the seminal vesicles (glands at the base of the bladder, which are connected to the prostate gland and help produce semen).
- Stage IV is advanced cancer. The cancer has spread to the lymph nodes and other tissues or organs.
Experts have devised treatments based on classification systems, including staging and tumor grade. However, there are no clear-cut answers on the best treatments for particular stages. In addition to staging, other factors must be considered. These factors include the patients age, overall health status, and personal preferences concerning side effects and quality of life. In addition to standard treatments, patients may also wish to consider enrolling in clinical trials of investigational treatments.
Depending on the cancer stage and other factors, patients have four main treatment options:
- Active surveillance, also called watchful waiting, involves monitoring the tumor for cancer progression to determine if and when treatment should be started.
- Surgery (radical prostatectomy) removes the prostate gland. The vessels that carry semen and surrounding tissue may also be removed. Studies indicate that compared to watchful waiting, radical prostatectomy may lower the risk of cancer recurrence and death, particularly for younger men with aggressive tumors. It is usually not appropriate for older men.
- Radiation therapy targets the tumor either externally (external beam radiation) or internally (implanted seeds).
- Androgen therapy, also called hormone therapy, uses orchiectomy (surgical removal of the testicles) or drugs to stop production of male hormones.
The U.S. National Cancer Institute recommends the following treatment options by cancer stage:
Stage I Treatment Options (Localized Cancer)
Tumors: T1a, N0, M0, G1, Stage A
- Active surveillance
- Radical prostatectomy, usually with pelvic lymphadenectomy, with or without radiation therapy after surgery
- External beam radiation therapy
- Implant radiation therapy (brachytherapy)
- Clinical trial options include high-intensity focused ultrasound
Click the icon to see an illustrated series detailing prostatectomy surgery.
Stage II Treatment Options (Localized Cancer)
Tumors: T1a - c, N0, M0, any G, Stage A2, B1, or B2
- Radical prostatectomy, usually with pelvic lymphadenectomy, with or without radiation therapy after surgery
- Active surveillance
- External beam radiation therapy with or without hormone therapy
- Implant radiation therapy (brachytherapy)
- Clinical trial options include radiation therapy with or without hormone therapy; ultrasound-guided cryosurgery; hormone therapy followed by radical prostatectomy
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:
- Compared with active surveillance, radical prostatectomy may lower the risk of cancer recurrence and death.
- For men at intermediate and high risk, adding androgen deprivation therapy to external beam radiation may improve survival. A higher dose of external beam radiation also improves the odds for survival.
- Initial (first-line) androgen deprivation therapy is seldom recommended for localized prostate cancer except for the relief of symptoms in patients with poor prognoses. Androgen deprivation therapy can increase the risks for diabetes and heart disease.
- Patients with localized prostate cancer should have the opportunity to enroll in clinical trials investigating new types of therapy.
Stage III Treatment Options (Locally Advanced Cancer)
Tumors: T3, N0, M0, any G, Stage C
- External beam radiation with or without androgen deprivation therapy (hormone therapy)
- Androgen deprivation therapy
- Radical prostatectomy, usually with pelvic lymphadenectomy, with or without radiation therapy following surgery
- Radiation therapy, androgen deprivation therapy or transurethral resection of the prostate (TURP) to relieve symptoms
- Clinical trial options include ultrasound-guided cryosurgery
Click the icon to see an illustrated series detailing transurethral resection of the prostate.
Stage IV Treatment Options (Advanced Cancer)
Tumors: Any T, any N, any M, any G, Stage D1 - D2
- Androgen deprivation therapy
- External beam radiation therapy with or without androgen deprivation therapy
- Radiation therapy or transurethral resection of the prostate (TURP) to relieve symptoms
- Active surveillance
- Clinical trial options include radical prostatectomy with surgery to remove both testicles (orchiectomy)
Recurrent or Persistent Prostate Cancer
If prostate cancer has been eliminated after initial treatment, PSA levels should drop to 0.5 ng/mL or less 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:
- If PSA levels are above 2.0 ng/mL, then cancer is most likely still present.
- If PSA levels are between 0.5 - 2.0 ng/mL, the situation is less clear.
(Note: 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 the cancer will recur during a man's lifetime. An actual cure is still possible if the cancer is localized within the prostate.
Treatment options for recurrent cancer dependend on various factors, including prior treatment, site of recurrence, coexistent illnesses, and individual patient considerations.
- Patients whose cancer recurs locally after prostatectomy: Radiation therapy, androgen deprivation therapy.
- Patients whose cancer recurs locally after radiation therapy: Androgen deprivation therapy, prostatectomy (very select patients).
- Patients whose recurrent cancer has spread: See treatment options for stage IV.
Comparing Side Effects of Treatments
Prostate cancer treatments can cause distressing side effects by impairing sexual function (impotence), 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 watchful waiting.
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:
- External beam radiation therapy provides the best results for recovery of sexual function.
- Nerve-sparing prostatectomy generally produces better sexual function than conventional radical prostatectomy.
- External beam radiation therapy produces better urinary control and sexual function than brachytherapy, but brachytherapy has better results for these side effects than radical prostatectomy.
- Radiotherapy (both brachytherapy and external beam radiation) generally causes more bowel problems than surgery, although this side effect usually improves after 1 year.
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:
- Men in their late 70s and older. More aggressive therapies (surgery and radiation) are usually recommended for men in their 50s and younger. The choice for men in their 60s and early 70s is more problematic. The general recommendation is that aggressive therapy is suitable for those who have a life expectancy of more than 10 years and who have localized but mid- to high-grade tumors. The tumor grade may be the best guide for determining the risks in choosing watchful waiting.
- Elderly men with early-stage (T0 - T2) low-grade tumors.
- Men with low-to-moderate (3 - 13 ng/mL) PSA levels.
Some experts 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 impotence and incontinence. However, some recent surveys suggest that more men are choosing treatment (especially surgery) over active surveillance. 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 70%, depending on tumor stage, tumor grade, and PSA levels. 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.
Candidates. Radical prostatectomy is a consideration for men who:
- Are in good health and with a life expectancy of 10 years or more. As average life expectancy in men has increased, more older men are becoming candidates for surgery. Complication rates are higher the older a man is, however.
- Have cancer that has not spread beyond the prostate gland.
- Have cancer that is potentially life threatening. (In general, a life-threatening tumor is indicated by volumes more than 0.2 cc and Gleason grade scores greater than 5.)
Radical Prostatectomy
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 incision can be made in one of the following regions:
- Retropubically (through the abdomen and under the pubic bone, exposing the entire surface of the prostate).
- Through the perineum (the skin between the scrotum and the anus).
The gland and other structures are then removed. The operation lasts 2 - 4 hours. Advanced surgical techniques, such as minilaparotomy and laparoscopy, are being developed for radical prostatectomy. These techniques use smaller incisions, are less invasive, and may cause fewer complications.
Click the icon to see an illustrated series detailing prostatectomy surgery.
Nerve-Sparing Techniques. Surgical procedures have been refined over the years, and many operations for localized low-grade prostate cancer now spare the nerves that control erection.
- A bilateral nerve-sparing procedure saves the nerves on both sides of the sex organs.
- A unilateral procedure saves nerves on only one side.
Nerve-sparing techniques may improve quality of life, by decreasing the occurrence of incontinence and impotence. The ability for sexual intercourse has been reported to recover in about a third of patients at 3 years and nearly 60% at 5 years after surgery. However, not all studies have achieved these results. (Rates vary depending on certain factors, such as the patient's age -- the younger the better -- and the skill of the surgeon.) In cases where the tumor is bulky and undifferentiated, nerve-sparing techniques may not be appropriate.
Convalescence. Patients remain hospitalized for up to 2 weeks. A temporary catheter used to pass urine is kept in place when the patient is sent home and usually removed about 3 weeks after the operation. The convalescent period at home is about a month. In general, younger patients with early-stage cancers recover fastest and experience the fewest side effects.
Complications from Radical Prostatectomy
Complication rates vary after radical prostatectomy and usually depend on the age of the patient and the experience of the surgeon and medical center. They can range from 4% in men in their 40s to 14% in men over age 70. Complication rates are 10 times higher in patients who have prostatectomy because of cancer recurrence after radiation treatment.
Complications include the usual risks of any surgery, such as blood clots, heart problems, infection, and bleeding. Complications specific to radical prostatectomy (incontinence, impotence, and contracture of the bladder neck) are discussed below. The mortality rate is very low, about 0.4%.
Quality of life usually improves shortly after surgery, and recovery from certain complications, such as incontinence and sexual function, can continue to occur even over years.
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 for nearly all men younger than age 70 and in the great majority of men older than 70.
Click the icon to see an image of catheterization.
If incontinence persists beyond a year, patients may require drug therapy or surgery. Collagen injections into the urethra, bladder neck suspension surgery, or a urinary sphincter implant may be helpful for men who have chronic incontinence. [For more information, see In-Depth Report #50: Urinary incontinence.]
Impotence. Studies suggest that about 40% of men have problems with erection after the procedure. Nerve-sparing procedures are proving to be helpful in reducing impotence as well as incontinence.
Sildenafil (Viagra) helps restore potency on average in about a third of patients. Alprostadil injections may also help restore erectile function. If these methods do not work, vacuum pumps are also an option. [For more information, see In-Depth Report #15: Erectile dysfunction.]
Even when erectile function is preserved, men may have other sexual problems:
- Erections may not be as rigid as before the operation.
- Orgasm and sexual sensation may be altered.
- Patients who retain potency may suffer from retrograde ejaculation, also known as dry ejaculation. During ejaculation, semen travels backward into the bladder, causing infertility.
Fecal Incontinence. Radical prostatectomy can also cause fecal incontinence.
Contracture of the Bladder Neck. Another common postsurgical complication is contracture of the bladder neck at the point where it has been stitched to the remainder of the urethra. Contracture usually occurs within the first 3 months after the operation, causing a sharp decrease in urinary stream. The condition can be treated by dilation or surgery on the bladder neck, and rarely recurs.
Pelvic Lymphadenectomy
Pelvic lymphadenectomy is the surgical removal of the pelvic lymph nodes. It is usually performed at the same time as prostatectomy. If the surgeon suspects that cancer has spread beyond the prostate, the surgeon will perform the lymphadenectomy as part of the operation. Some surgeons do this procedure as a matter of course when performing prostatectomy, since it has few complications and adds information on the state of the disease. The lymph nodes are removed through an incision in the lower part of the abdomen, using conventional surgery or laparoscopy, a less invasive variation. The nodes are immediately examined. If they show signs of cancer, metastasis has occurred. In such cases, the operation is usually stopped and the patient is offered radiation or hormone treatments.
Click the icon to see an image of the pelvic lymph nodes.
Transurethral Resection of the Prostate (TURP)
Transurethral resection of the prostate (TURP) involves removing a section of the prostate with a surgical instrument (resectoscope) that is inserted through the urethra. TURP may be used to control urinary symptoms in men who are not good candidates for curative therapy due to advanced age, health status, or other reasons. TURP is also used as a treatment for benign prostatic hyperplasia (BPH).
Cryosurgery (Cryoablation)
Cryosurgery is an alternative to standard prostatectomy. 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. Patients can leave the hospital in 2 - 3 days.
Equal or superior efficacy has not yet been shown in randomized controlled trials and this therapy is not yet considered first line.
Candidates. Cryosurgery may be considered for patients with:
- Early stage local cancer
- Cancer that has recurred after radiation treatments
- Large primary tumors that the surgeon wishes to reduce
- Possibly tumors that have spread beyond the prostate if they have not yet reached the lymph nodes
Strong predictors of treatment failure include:
- A history of both hormonal and radiation treatments
- Tumor grades 8 and above
- PSA levels of more than 10 ng/mL
Complications. Complications are similar to those of standard prostatectomy, but incontinence rates are much lower. Impotence rates, however, are much higher. Nevertheless, 96% of patients report that they are satisfied with the results. Incontinence and other side effects may be higher in patients who have had previous radiation treatments. Other significant complications include scarring and narrowing of the urethra, and fistulas (abnormal passages from internal organs to the skin or between two internal organs).
Radiation Therapy
Radiation is considered for men with one or more of the following characteristics:
- Being older and, particularly, having other medical problems.
- Cancer has extended beyond the prostate capsule but has not spread to the lymph nodes or further.
- Being a good surgical candidate, but having decided against an operation. The risk for incontinence (less than 10%) is much lower than with surgery, although bowel problems occur in about a third of patients. Impotence rates are about the same.
The two major radiation treatments are:
- External beam radiation
- Brachytherapy (internal radiation)
Both treatments have generally equal success rates. Evidence indicates that the two therapies work equally well for treating localized prostate cancer. In some cases, both techniques may be used in high-risk patients.
External Beam Radiation
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. Men who have had transurethral resection of the prostate (TURP) or have a history of lower urinary tract symptoms may be particularly good candidates for 3D conformal techniques.
Patients considering external beam radiation should be aware that higher radiation doses may reduce the risk for cancer recurrence and improve survival outcome.
Brachytherapy
Brachytherapy is an outpatient 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 and, even with experienced doctors, the distribution of radioactive seeds is uneven in 15% of cases, increasing the risk for insufficient doses.
It is common for PSA levels to temporarily rise, or "bounce," following seed implantation without it being a signal for cancer recurrence. This effect can produce anxiety and can interfere with the diagnosis of true recurrence.
Brachytherapy is useful for select patients, specifically those with prostate volumes less than 60 mL and who have early-stage prostate cancer (T1 or T2 tumors, a Gleason grade lower than 7, and PSA levels below 10 ng/mL). It may be beneficial in patients with inflammatory bowel disease or with cancer close to the bowel. Poorer candidates for brachytherapy include men who have had TURP and patients with advanced cancer, high-grade tumors, or very enlarged prostate glands.
Complications from Radiation
The side effects of radiation therapy include most of those of surgery, but the risks for impotence and urinary incontinence are considerably lower.
Gastrointestinal Complications. Complications in the gastrointestinal 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. A few patients have diarrhea flare-ups for years afterwards. Less than 1% suffer more serious intestinal problems. Radiation enteritis (infection in the intestinal tract) may cause bloody diarrhea.
There is potential for injury to the rectum with brachytherapy. Ulcers in the rectum occur in more than 10% of patients, but the risk decreases with greater experience in the technique.
Urinary Problems. The risk for incontinence is about 7 - 20%. Patients treated with radiation may experience a painful, but usually temporary, urinary tract inflammation. About 10 - 15% of patients develop a long-term urgent and frequent need to void their bladder. Brachytherapy is especially associated with a risk for urinary incontinence.
Impotence. Recent reviews indicate that external beam radiation is better at preserving sexual function than brachytherapy, although both types of radiation therapy generally produce better sexual function results than surgery. Sildenafil (Viagra) may help many men with impotence following radiation therapy for local prostate cancer. Early use of both alprostadil injections and sildenafil may be even more effective. Other treatments may also be useful. [For more information, see In-Depth Report #15: Erectile dysfunction.]
Adjuvant and Salvage Radiation
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:
- Adjuvant radiation is radiation therapy performed within 6 months after radical prostatectomy. One area of controversy is whether to use adjuvant radiation after surgery on patients whose PSA levels are very low or undetectable but who have other test results that indicate the cancer is likely to spread. Patients with adverse findings and low PSA have to weigh the potential complications of radiation therapy against the odds of recurrence without it, which are about 20 - 30%.
- Salvage radiation is radiation therapy more than 6 months after surgery. Some studies suggest that salvage radiation could be more beneficial than previously thought, even for men with aggressive prostate cancer.
Hormone Therapy and Chemotherapy
Androgen Deprivation Therapy (Hormone Therapy)
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). Side effects can include impotence, loss of sexual desire, decreased bone density, decreased muscle mass, hot flashes, depression, fatigue, weight gain, enlarged breasts, and high cholesterol levels. New studies suggest that androgen deprivation therapy increases the risk of heart attack, stroke, and diabetes.
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 nonsteroidal 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
Orchiectomy is the surgical removal of the testicles. 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. Combining orchiectomy with antiandrogen drug therapy adds a modest benefit.
The median survival rate after the operation is about 55% over a 40-month period. An estimated 25% of patients survive 5 years or more. Nevertheless, orchiectomy, although irreversible, may produce fewer adverse effects than hormonal drugs, and interestingly, many patients report significantly higher quality of life after orchiectomy than those who opt for hormonal treatment, particularly total androgen ablation. Because orchiectomy is irreversible, about 75% of patients with advanced prostate cancer choose non-surgical androgen deprivation. Like all androgen deprivation therapies, orchiectomy increases the risk for osteoporosis.
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.
LHRH Agonists
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.
Testosterone and PSA Surges. 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. Administering flutamide, a drug known as an antiandrogen, for 2 weeks prior to LHRH agonists may not only prevent PSA surge but also induce early declines in PSA levels.
Side Effects. Side effects include hot flashes and occasionally nipple and breast tenderness.
Anti-Androgens
Anti-androgens are drugs used to block the effects of testosterone. They are used alone or in maximal androgen blockage (MAB), in which they are combined with LHRH agonists or orchiectomy to completely block androgen hormones.
The main anti-androgen drugs include:
- Flutamide (Eulexin, Drogenil). Flutamide has produced extended response in some patients. Side effects may include diarrhea and liver damage, which has been fatal in rare cases; liver function must be monitored closely.
- Nilutamide (Nilandron). Nilutamide is associated with reversible interstitial pneumonitis, nausea, alcohol intolerance, and visual disturbances.
- Bicalutamide (Casodex). Bicalutamide is effective and appears to have fewer severe side effects than other anti-androgens, including loss of sexual interest, osteoporosis, visual disturbance, and interstitial pneumonia. This drug is proving to have survival rates equal to those of maximal androgen blockage.
- Cyproterone combined with estrogen may prevent the testosterone surge that occurs with LHRH agonists.
Other Drugs Used in Hormone Therapy
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.
Combining Hormonal Therapy with Radiation or Surgery
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.
Complications of Androgen Deprivation Therapy
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:
- Osteoporosis, the loss of bone density. A number of medications, especially bisphosphonates, are available to help prevent or reduce bone loss.
- Diarrhea
- Loss of muscle mass
- Psychological disturbances
- Fatigue
- Sexual dysfunction and loss of sexual drive
- Swelling of the breasts (gynecomastia)
- Nausea and vomiting
- Hair loss
- Anemia
In addition, there is growing evidence that androgen deprivation therapy increases the risks for diabetes and heart disease.
Chemotherapy for Hormone-Resistant Cancer
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
- www.cancer.gov -- National Cancer Institute
- www.cancer.org -- American Cancer Society
- www.asco.org -- American Society of Clinical Oncology
- www.cancer.net/portal/site/patient -- Cancer.Net
- www.prostatecancerfoundation.org -- Prostate Cancer Foundation
- www.fightprostatecancer.org -- National Prostate Cancer Coalition
- www.urologyhealth.org -- Urology Health
- www.nccn.org -- National Comprehensive Cancer Network
- www.cdc.gov/cancer/prostate -- CDC Cancer Prevention and Control
- www.psa-rising.com -- PSA Rising: Prostate Cancer Survivor Info
- www.ustoo.org -- Us Too! Prostate Cancer Education and Support
- www.cancer.gov/clinicaltrials -- Find clinical trials
References
D'Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA. 2008 Jan 23;299(3):289-95..
Keating NL, O'Malley AJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. J Clin Oncol. 2006 Sep 20;24(27):4448-56.
Lawson KA, Wright ME, Subar A, Mouw T, Hollenbeck A, Schatzkin A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst. 2007 May 16;99(10):754-64.
Leman ES, Cannon GW, Trock BJ, Sokoll LJ, Chan DW, Mangold L, et al. EPCA-2: a highly specific serum marker for prostate cancer. Urology. 2007 Apr;69(4):714-20.
Lin K, Lipsitz R, Miller T, Janakiraman S; U.S. Preventive Services Task Force. Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann Intern Med. 2008 Aug 5;149(3):192-9.
Lim LS, Sherin K; ACPM Prevention Practice Committee. Screening for prostate cancer in U.S. men ACPM position statement on preventive practice. Am J Prev Med. 2008 Feb;34(2):164-70.
Litwin MS, Gore JL, Kwan L, Brandeis JM, Lee SP, Withers HR, et al. Quality of life after surgery, external beam irradiation, or brachytherapy for early-stage prostate cancer. Cancer. 2007 Jun 1;109(11):2239-47.
Loblaw DA, Virgo KS, Nam R, Somerfield MR, Ben-Josef E, Mendelson DS, et al. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol. 2007 Apr 20;25(12):1596-605. Epub 2007 Apr 2.
Lu-Yao GL, Albertsen PC, Moore DF, Shih W, Lin Y, DiPaola RS, et al. Survival following primary androgen deprivation therapy among men with localized prostate cancer. JAMA. 2008 Jul 9;300(2):173-81.
Sanda MG, Dunn RL, Michalski J, Sandler HM, Northouse L, Hembroff L, et al. Quality of life and satisfaction with outcome among prostate-cancer survivors. N Engl J Med. 2008 Mar 20;358(12):1250-61.
Shelley M, Wilt TJ, Coles B, Mason MD. Cryotherapy for localised prostate cancer. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD005010.
Thompson I, Thrasher JB, Aus G, Burnett AL, Canby-Hagino ED, et al. Guideline for the management of clinically localized prostate cancer: 2007 update. J Urol. 2007 Jun;177(6):2106-31.
U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008 Aug 5;149(3):185-91.
Walsh PC, DeWeese TL, Eisenberger MA. Clinical practice. Localized prostate cancer. N Engl J Med. 2007 Dec 27;357(26):2696-705.
Walter LC, Bertenthal D, Lindquist K, Konety BR. PSA screening among elderly men with limited life expectancies. JAMA. 2006 Nov 15;296(19):2336-42.
Wilt TJ, MacDonald R, Hagerty K, Schellhammer P, Kramer BS.Five-alpha-reductase inhibitors for prostate cancer prevention. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD007091.
Wilt TJ, MacDonald R, Rutks I, Shamliyan TA, Taylor BC, Kane RL. Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer. Ann Intern Med. 2008 Mar 18;148(6):435-48. Epub 2008 Feb 4.
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.
