Portions from: www.healthandage.com/html/well_connected/pdf/doc33.pdf [Condensed From an overly-long PDF file.]
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SEXUAL FREQUENCY: Does it reduce incidence of prostate problems? |
|FUNCTIONS of the Prostate Gland|
ZINC can increase cancer risk
ASPIRIN can reduce risk
Prostate cancer tends to be slow growing compared to others. As many as 90% of all cases 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."
Hormones and Prostate Cancer. Male hormones (androgens) play major roles in the development of prostate cancer. Some research, for example, reported a higher risk with increasing testosterone and a lower risk with increasing estrogen levels. Dihydrotestosterone(DHT) is the principal male hormone in the prostate gland. It affects the size of the prostate gland itself and may play a role in prostate cancer. Nevertheless, researchers have not yet fully clarified the specific mechanisms that may be important in the development of this disease. Most likely, genetic mutations affecting androgens trigger the process. Certain growth hormones, such as insulin-like growth factor-I, are unrelated to testosterone and may increase the risk for prostate cancer.
The Prostate Gland
Description 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:
Smooth muscle cells, which contract during sex and squeeze the fluid from the glandular cells into the urethra, where it mixes with sperm and other fluids to make semen
• Glandular cells, which produce a milky fluid that liquefies semen.• Stromal cells (which form the structure of the prostate)
• 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: 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.
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 about the mid-forties, when, in most men, the prostate begins to enlarge again through a process of cell multiplication.
Prognosis Prostate cancer is the most common male cancer in the US. Only lung cancer causes more cancer deaths in American men. The lifetime probability of developing prostate cancer is 8%. Each year, approximately 180,000 men in the United States will be diagnosed with prostate cancer, and about 32,200 will die from the disease. It should be noted that because older men often die while suffering from both prostate cancer and other serious medical disorders, official records may attribute many deaths to prostate cancer that are actually due to other causes. Some researchers believe that deaths caused by prostate cancer are misreported (mostly over diagnosed) by as much as 10% to 20%.
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. Cure rates can be as high as 98% in some cases.
Prognosis in Late Stage Disease Locally Advanced: 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.
Prognosis After Recurrence If cancer recurs after initial treatment, hormone treatments in such cases can prolong survival for years.
Risk Factors The major risk factors for prostate cancer include genetic, dietary, and environmental factors that effect male hormones (androgens).
Age Prostate cancer is the most common cancer in the US after skin cancers, and the second leading cause of cancer deaths among men. As the population ages, this number is expected to increase. Prostate cancer occurs almost exclusively in men over the age of 40 and most often after the age of 50. 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 it nearly always die of something else.
Family History and Genetic Factors Heredity may play a role in prostate cancers. Having one family member with prostate cancer doubles a man's own risk and having three family members poses an 11-fold risk for the disease. Some early-onset cases of prostate cancer associated with specific inherited genes have been identified, but they account for a small percentage of cases.
Ethnicity African American men have the world's highest risk for prostate cancer, more than 50% higher than the risk for Caucasian American males. The disease is also more lethal among African Americans. Of note, men in Asia have lower risks for prostate cancer, but their risk increases if they move to North America. Thus, there are 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. For example, a 2000 study at a Veterans hospital where all the men had equal care reported no differences in tumor properties between African American and Caucasian men
.Dietary Factors. Dietary factors may play some small role in the higher risk in African men. This is suggested by the fact that prostate cancer is rare in many parts of Africa.
Biologic Factors. Some evidence suggests that African American and Asian men have certain genetic factors that may affect male hormones differently and so help account for the higher risk in the first group and the lower risk in the second. Other research reports that African American men have lower levels than Caucasian men of a protein called "insulin-like growth factor binding protein 3" (IGFBP3), which may protect against cancer. ("Insulin-like growth factor-I" is a hormone that may increase the risk for prostate cancer in any man.) Still, more research is needed.
[NOTE: "insulin-like growth factor binding protein 3" is of an "unknown-origin" in medical literature. The name suggests that it is a healthy product of the body; However, it is only mentioned as a "marker" indicating the presence of cancer. No source I've been able to find identifies an organ that secretes it, so it is merely an object of study.Higher PSA Levels. African American men also tend to have higher PSA levels than Caucasians. They are over diagnosed with prostate cancer by 37% compared to 15% in Caucasians using PSA screening tests.
The other one, "Insulin-like growth factor-I", the "good" one that accompanies resistance to cancer, is likewise mysterious. They are likely the byproducts of other, more substantial causes for either prognosis. - Ed.]
High Exposure to Chemicals and Electromagnetic Fields: Chemicals. Men whose work involves heavy labor and those exposed to certain metals and chemicals, including cadmium, dimethylformamide, and acrylonitrile, may be at higher risk for prostate cancer. Some studies have indicated that farmers might be at higher risk. A 2001 study concluded that certain leisure activities may expose men to the same chemicals including:
Home or furniture maintenance
.• Painting, stripping, or varnishing furniture.
• Activities that involve exposure to lubricating oils or greases, metal dust, or pesticides or garden sprays
Infection and Inflammation.
Some association has been seen between prostate cancer and bacterial or viral infections, such as herpes virus, human papilloma virus, and cytomegalo virus in inherited prostate cancer cases. Although some of these agents are sexually transmitted, the association with sexual activity is still unclear. One theory suggests that in men with such genetic susceptibilities, any sexually transmitted infection can produce a chronic inflammatory condition in the prostate, which, over time, can initiate cancerous changes. Such beliefs are supported by a possible lower risk in men who take nonsteroidal anti-inflammatory drugs [i.e., aspirin] (NSAIDs). More research is needed.
Other Factors Associated with Prostate Cancer
Nonmelanoma Skin Cancers and Sunlight. One study reported that patients with prostate cancer and a history of nonmelanoma skin may have a higher risk for a poorer outlook. Such skin cancers are highly associated with exposure to sunlight. It should be noted, however, that sunlight triggers production of vitamin D in the body, which may help protect against prostate cancer. Prostate cancer rates are, in fact, lower in southern, sunny regions.
Vasectomy. Because testosterone levels remain higher for a longer period in men who had vasectomy, experts have postulated that such men have a greater chance for developing the cancer. A 2002 meta-analysis of 22 studies indicated a higher risk with vasectomy, but most recent studies are reporting no higher danger. A rigorous 2002 study from New Zealand, for example, which has the highest vasectomy rates in the world, found no increased risk of prostate cancer from the procedure, even 25 years after the operation. A 2002 study in California, in fact, reported a lower risk for prostate cancer in men who had had vasectomies. It is possible that the higher rates reported in the early studies may simply be due to earlier prostate screening in men who have had vasectomies. Indeed one study reported that about 25%of physicians screened men with vasectomies earlier for prostate cancer than those without the operation. [For more information, see Well-Connected Report #37 Vasectomy.]
A Western lifestyle is associated with prostate cancer, so obesity, high-meat intake, and dietary fats have been intensively studied. Results have been inconsistent, however. Certain factors, such as carcinogenic compounds in well-cooked meat or high-calorie intake, may help explain the associations between such dietary factors and cancer risk.
Obesity and High- Calorie Intake. A 2001 study reported that obesity was associated with a modest increase in prostate cancer mortality, although not with the risk for prostate cancer itself. Some evidence suggests that it is a high-calorie intake rather than obesity or fat intake increases the risk for prostate cancer.
Fats. Some, but not all, studies have found some association between high fat-intake and prostate cancer. This association may be explained by other suspected dietary factors for prostate cancer, such high-calorie diet, high meat intake, and calcium (found in dairy products), which are all also associated with fat intake. The effects of specific fatty acids (compounds that make up fats) may also help clarify the role of fats in prostate cancer.
Omega-3 Fatty Acids. Some research has suggested that omega-3 fatty acid may be protective. Omega-3 fatty acids are found in plants (e.g., soybeans, rapeseeds [canola oil], flaxseed, and certain nuts and seeds) and fish oil (e.g., salmon, sardines, halibut, swordfish, and tuna). Some studies have reported a lower risk for prostate cancer in men who ate fish frequently (two or more times a week)
Alpha-Linolenic and Omega-6 Fatty Acids. On the other hand, some research has indicated that alpha-linolenic acid and total omega-6 fatty acids may increase the risk of prostate cancer. Sources of these fatty acids are the polyunsaturated vegetable oils (e.g., corn, safflower, soybean, canola, and sunflower oil) , which constitute most of the oils consumed in the U.S.
Meat and High-Temperature Cooking. Some evidence suggests that a high intake of red meat raises the risk for prostate cancer (also possibly colon cancer). Because red meat is often in fat, such findings may explain the inconsistencies found in studies that simply look at fat content as a risk for prostate cancer. Perhaps of more importance, high-temperature cooking (grilling, broiling, or pan-frying) of meat or poultry has been specifically associated with increased risk for cancer in some studies, Over-cooking meat increases the amount of compounds called heterocyclic amines, which has been associated with cancerous changes in general and prostate cancer in particular, at least in some studies. Cooking meats in liquid does not appear to increase these compounds. As with all dietary studies, some have observed no association between high intake of well-cooked meat and prostate cancer. Thus, this is a controversial area that requires more research
Vegetarian Diet. Small studies suggest that a vegetarian diet may be protective. Specific foods may be especially helpful in reducing the risk prostate cancer:
Whole grain cereals, seeds, and nuts have been associated with a lower risk for prostate cancer. Part of this protection may be due to their high fiber content. Fiber binds to sex steroids and is excreted, carrying the hormones with it. Whole grains also contain selenium, a rare element that may have some protective properties.
• Many studies have reported a significantly lower risk for prostate cancer with high intake of cooked tomatoes, which are high in a beneficial plant chemical called lycopene. (Some studies have not reported such protection, although intake may have been too low.)
Soy may also be protective, which may partially explain the low rate of prostate cancer observed in Japanese men and vegetarians (who typically use soy as a protein replacement). Theoretically soy, which is a rich source of an estrogen-like plant compound, may inhibit hormones that promote prostate cancer. Laboratory studies are mixed on such effects, however. Bowman-Birk inhibitor is a soybean-derived product that is being investigated for its effects on prostate health and possible prevention of prostate cancer. A 2001 trial of a concentrated form was associated with a decrease in serum PSA levels and in prostate volume. There is some concern, however, that such agents may increase the risk for pancreatic cancer
Cruciferous vegetables (e.g., cauliflower and broccoli) have cancer-fighting chemicals
.• Boron-rich foods (e.g., nuts, red grapes, avocados, and dried fruits) may also be protective.
Dairy Products, Calcium, and Vitamin D. Studies have reported an association between consuming large amounts of dairy products and a modestly increased risk for prostate cancer. (Moderate intake has not been associated with a higher risk. ) That is some evidence that calcium (contained in dairy products) may increase the risk for prostate cancer by reducing levels of the most active form of vitamin D (1,25 dihydroxy vitamin D), which may protect against prostate cancer. In fact, some research is focusing on prostate treatments using vitamin D analogs. There is still no clear proof, however, that high calcium and low vitamin D levels pose a significant risk for prostate cancer. And, it should be noted that evidence strongly suggests that calcium reduces the risk for colon cancer.
Vitamins and Mineral Supplements Vitamin E. Vitamin E is being investigated for possible protection against prostate cancer. To date, four trials have found that vitamin E may provide some reduction in risk for past and current smokers and for men with vitamin E deficiencies. Of concern was an association in one study of a higher risk for aggressive prostate cancer in nonsmoking men who took high doses of vitamin E (100 IU or greater).
Selenium. Selenium is a trace mineral found in Brazil nuts, most red meats, poultry, shellfish, and dark mushrooms. In laboratory studies, selenium has acted directly on prostate cancer cells, stimulating cell death and inhibiting growth. In one 2003 study, selenium levels were measured in toenail clippings. Those with the highest levels had the lowest risk for prostate cancer. The findings were particularly pronounced in ex-smokers. Other studies on significant protection from selenium supplements against prostate cancer, however, have been weak. It is possible that supplements may benefit only those who have selenium deficiencies. In any case, as with other dietary factors, selenium alone is unlikely to be significant in protection against prostate cancer. It should be noted that high amounts of selenium can be toxic, and can cause hair and nail loss. It has also been associated with a higher risk for skin cancer.
Zinc. Zinc is of interest because it accumulates to the highest levels in a man's body in either a normal prostate or one enlarged from benign prostate hyperplasia. Some laboratory studies suggest that zinc might inhibit activation of prostate cancer cells. A 2003 study, however, reported that men taking zinc supplements in high doses (100 mg) had a higher risk for advanced prostate cancer. Of note, such men also took higher levels of calcium, iron, and other supplements that might have biased these results. More research is needed to determine the role of zinc on prostate health.
Alcohol Moderate to heavy alcohol intake (22 to 56 drinks a week) has been associated with increased risk.
Exercise Exercise is beneficial for general health and it temporarily lowers testosterone levels. Studies on its effects on prostate cancer are mixed. It may not have much effect on men who are at low risk to begin with. A 1998 study suggested that although exercise had no protective effect overall on prostate cancer, vigorous exercise was associated with a lower risk for metastatic prostate cancer. Exercise is an important component of any health-protective program.
Finasteride (Proscar) Finasteride (Proscar) blocks an enzyme that converts testosterone to dehydro-epiandrosterone (DHEA), the form of the male hormone that stimulates the prostate. The agent is used to shrink the prostate in men with benign prostatic hyperplasia. It is, therefore, being investigated for prevention of prostate cancer. A large 2003 study suggested that taking it may reduce the risk for prostate cancer by 25%. (On the negative side, the drug can impair sexual function.) The study had some problems, however. For example, in the placebo group, the rate of prostate cancer was much higher than in other studies. Comparing the lower risk from Proscar to other studies, then, would make the reduction less significant. Also when men taking Proscar did develop prostate cancer, the tumor cells tended to be aggressive types. Experts are investigating whether this observation has any significance. One possibility is that the drug actually stimulates high-grade cancer cells. Until more is known, experts do not recommend this agent for prevention.
Sexual Activity Frequent ejaculations from masturbation or sexual activity has been associated with a lower risk for prostate cancer. Some experts speculate that certain carcinogens may be concentrated in prostate fluid, so that frequent ejaculation helps eliminate them. Of note, risky sexual activity, such as with multiple partners, increases the risk for sexually transmitted disease, which in turn may increase the risk for prostate cancer.
Nonsteroidal Anti-inflammatory Drugs (NSAIDs) There is some evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) offer some protection against prostate cancer. NSAIDs suppress chemical in the body called COX-2, a protein that may cause prostate cancer cells to spread. Standard NSAIDs include aspirin, ibuprofen (Advil), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox). Many other NSAIDs, such as sulindac (Clinoril), are available only by prescription and are being studied for protection. Newer agents, such as celecoxib (Celebrex), rofecoxib (Vioxx), valdecoxib (Bextra), and meloxicam (Mobic) may warrant specific investigation. A 2002 study reported a 50% reduction in the risk for prostate cancer in men over 60 who took a daily NSAID, although conclusive evidence is still needed.
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 herald the occurrence of metastases. 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. [Most of these symptoms are the same in the following benign conditions:]
Benign Conditions with Similar Symptoms:
Benign Prostatic Hyperplasia (BPH)In up to half of men in their fourth decade, 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 Well-Connected 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.
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
The PSA blood test is widely available for screening men for prostate cancer. However, 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 treatments for many men who, considering the slow growth of the cancer, might derive no benefits from them.
Standard Screening Tests for Early Detection:
Currently, two standard tests are used for early detection of prostate cancer:
1. Digital rectal examination (DRE). With the DRE, a physician palpates the prostate in order to feel lumps or masses.
2. 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. If the digital rectal examination indicates the possible presence of cancer, regardless of the PSA results, a physician may also obtain a visual image of the prostate through an ultrasound procedure called transrectal ultrasonography(TRUS). Only a biopsy, however, in which a tiny sample of prostate tissue is surgically removed, can actually confirm a diagnosis of prostate cancer.
Candidates for Annual Screening.
Until major studies report on the survival benefits of prostate screening, expert groups current recommend the following: Men aged 50 to 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 two years thereafter.)• Men with a family history of prostate cancer and all African-American men should consider annual screening at about age 40. The best age to start annual screening is under debate. Some experts advocate performing a first PSA test in all men aged 40 and then monitoring anyone whose PSA levels are over 0.60 ng/mL. They argue that such men are at high risk for developing prostate cancer within 25 years.
Accuracy of Screening Tests:
DRE alone, PSA alone, and in Combination with DRE: Chance of Cancer: Only 20% of men with abnormal DREs have cancer. Unfortunately, 70% of prostate cancers detected with DRE alone have already spread beyond the prostate gland. The odds of cancer with PSA readings are thefollowing:3 ng/mL or below indicates 2% or less chance of cancer.• 3 to 10 ng/mL indicates about a 25%chance of cancer.• 10 ng/mL and over indicates a very strong chance.• Men who with abnormal results from both DRE plus PSA tests have a 60% chance for cancer.
Risk of Missed Cancers with Normal Results: About 60% of men who have prostate cancer have normal DRE results. Some evidence suggests that only performing biopsies at levels above 4.0 would miss over 80% of cancers present below that level in men under 60 years and 65% in older men. As a result, some experts recommend biopsies with PSA levels at 3.0 or below in young men. Still, cancer at low PSA levels is very uncommon, particularly in younger men.
Digital Rectal Exam (DRE): About 90% of all prostate cancers arise in the outer part of the prostate where they may be detected by a digital rectal exam (DRE), which is the simplest and most widely-performed screening procedure. The doctor inserts a gloved and lubricated finger into the patient's rectum and feels the prostate for bumps or other abnormalities. The exam is quick and painless but some men find it embarrassing. It is not very accurate in detecting early cancers, but studies indicate that regular DREs still save lives.
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. (Of note: some experts urge biopsies even if PSA levels fall below 4.0 mg, particularly in men under 60, since lower levels do not necessarily rule out cancer.)
Abnormal digital rectal examination (DRE). Men with abnormal results from both tests have 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.
Ethnicity. Normal levels in Caucasian males may be different from those for African-American or Asian men. For example, using PSA screening, one study suggested that 15% of Caucasians and 37% of African-Americans are over diagnosed with prostate cancer based upon PSA results. Some experts believe that there should be different scales for determining risk among these groups, but there is still not enough information to determine a specific range for various ethnic groups.
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 experts 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% and 56% of patients with BPH have elevated PSA levels. Certain surgical treatments for this condition can also elevate PSA.
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.) In one study, screening for prostatitis increased the accuracy of the PSA test significantly and reduced the number of unnecessary biopsies.
Other Noncancerous Conditions.
Other noncancerous conditions that can increase PSA levels include surgical procedures for BPH, acute urinary retention, digital rectal examinations (DREs), and prostate biopsies themselves. Ejaculation within 48 hours before testing can raise PSA levels, although one study suggested that this occurs only when PSA levels were already elevated.
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 indicates cancer:
[NOTE: "Free PSA" & "Total PSA" measure different conditions, as indicated below. Clarify which tests are being used whenever taking a "PSA" ]A free-to-total PSA ratio of 20% or lower, plus total PSA levels of 4 to 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).
• Some studies have reported that adding a test for free PSA may improve prostate cancer detection by roughly 40% and may also reduce the need for unnecessary biopsies.
In addition, any cancers that the test misses would not develop into significant disease for many years, providing ample opportunity to identify them before they became serious. Not all studies support its advantages, however, compared to measuring total PSA alone, and to date there is no consensus among physicians for how it can be used.
Complexed PSA Test:
Complexed PSA (cPSA) is a form of circulating PSA that is bound to a molecule calledalpha1-antichymotrypsin. It represents about 90% of the total PSA in men and is significantly higher in men with prostate cancer than in those with BPH. To date, studies have reported conflicting results on its benefits for diagnosing prostate cancer, although a major 2002 European study was very favorable.
Transition Zone PSA Test:
Some tests have been developed to measure the density of the PSA in the transition zone of the prostate gland. (The transition zone is the central area of the prostate that wraps around the urethra.) A major comparison study in 2002 reported more accurate results than with complexed PSA.
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: Initial Biopsies. If preliminary tests raise the suspicion of cancer, physicians will perform a biopsy. Biopsy is used to diagnose prostate cancer, and is a very accurate method for predicting the severity of an existing cancer. It should be noted that biopsies can still miss cancers if they are very small.
The standard method is called a core biopsy, which uses a spring-loaded biopsy device inserted into the rectum. The device propels a needle into the prostate, obtaining a core of tissue, which is examined by pathologists.
Fine Needle Aspiration:
A more recent procedure called fine needle aspiration is less painful and may be as accurate as a core biopsy if the sample obtained is sufficient for analysis and if it is analyzed by a skilled pathologist.
More than half of the men who have a biopsy experience discomfort and anxiety, with men under 60 reporting higher levels of discomfort than older men. Taking a sedative an hour or two before the procedure can help reduce distress. Complications of biopsy are low, but urinary tract infection, fever, or bleeding occurs in 0.1 to 4%.
Repeat Biopsies. 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, such as in the following circumstances:
PSA levels are high. Two or more biopsies may be taken if a man has very high PSA levels and still has normal results on a biopsy. Even men with mildly elevated PSA (between 4 and 10 ng/mL) who test negative may be given a repeat biopsy. Cancer will be detected in about 10% of this group. Whether a third biopsy is useful in these men if they still test negative after a second biopsy is uncertain.
Also, biopies are recommended if:
DRE results are abnormal; Ultrasound results are abnormal; The initial biopsy yields microscopic findings that are suspicious.
In a 2001 study, in men with PSA levels of 4 to 10 ng/mL who did not show signs of cancer on the first biopsy, the following cancer rates were reported on subsequent biopsies: Second biopsy: 10% cancer rates. Third biopsy: 5% Fourth biopsy: 4%. The cancers found in third and fourth biopsies tended to be nonaggressive with favorable outlooks.
Biological Markers: A number of biological factors are being used or investigated as markers for cancer or its severity.
Testosterone Levels Higher total testosterone levels may increase the risk for metastasis. A 2000 study found an association with low free testosterone and more extensive prostate cancer, suggesting free testosterone could be a marker for aggressive disease. (Free testosterone, as with free PSA, is not chemically bound.)
Genetic Markers. Researchers have identified a genetic marker (EZH2), which may prove to be an important marker for aggressive prostate cancer. It may, in fact, prove to be a better predictor of outcome than the tumor grade, stage, or surgical margins. Other genes beings studied are those that regulate tumor growth (e.g., p53, p27, bcl-2).
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.
"T" for tumor; "N" for regional lymph nodes. "M" for metastasis.
T followed by numbers 0 through 4 refers to the size and extent of the tumor itself.
T1; T1a; T1b; T2: T2a: T2b: T2c: T3: T4:
N0: N1A: N2A: N3A:
M0: M1a: M1b: 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 A = TNM Stage T1; Jewett Stage B = TNM Stage T2; Jewett Stage C = TNM Stage T3, T4; Jewett Stage D = TNM Stages N1, N2, N3, M1;
External-Beam Radiation & Brachytherapy
Advances in both treatments have been generally equivalent in success rates. In some cases, both techniques may be used in high-risk patients.
External-Beam Radiation: In external-beam radiation therapy, a physician focuses a beam of radiation directly on the tumor for 35 three-minute treatments, five times a week, over seven weeks. 3-D conformal techniques use computers and a three-dimensional image of the prostate to provide precise targeting of the tumor using high-dose radiation beams. It allows high doses and 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.
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.
Choosing Hormonal Treatments
Hormonal treatment uses drugs or surgery (orchiectomy) to suppress or block male hormones (androgen), particularly testosterone and dihydro-testosterone. Hormone therapy is used for advanced and metastatic cases and may be used in localized cases.
Androgen-Suppression Therapy: Treatments that block or suppress androgens (male hormones) are often the appropriate response to rising PSA levels after treatment failure. There has been some debate over whether to start this therapy as soon as PSA levels rise or wait until symptoms develop.
Therapies that suppress male hormones (androgens) are the mainstay treatment for Stage IV cancer. Such therapies may be in the form of hormonal drugs, orchiectomy (surgical removal of the testicles, or "castration"), or both. They have significant side effects and possible long-term complications, however.
Specific Treatments Used to Block Androgen. Androgen-suppression treatments include the following: Hormonal Drugs. The primary agents used for suppressing androgens are called luteinizing hormone-releasing hormone (LH-RH) agonists.
Orchiectomy is surgical removal of the testicles. It is the single most effective method of reducing androgen hormones, but it is considered an extreme procedure. The operation can be done on an outpatient basis, through a tiny incision in the scrotum, and is relatively pain-free.
Sexual Effects. Many men can still achieve erection after orchiectomy, but there is almost always a decline in sexual drive. Men who cannot achieve erection may be candidates for a penile implant. Patients do not experience a reversal of sex characteristics: the voice does not change and body hair is not affected.
Quality of Life. Interestingly, patients who choose this option report significantly higher quality of life afterward than those who opt for hormonal treatment, particularly total androgen ablation. Although the operation impairs sexuality, it causes less fatigue, physical dysfunction, and psychological distress than other treatments for advanced cancer, excluding no treatment at all. These studies, however, did not compare orchiectomy to intermittent hormonal therapy, which may prove to have psychological benefits.
Osteoporosis. Like all androgen deprivation therapies, orchiectomy increases the risk for osteoporosis, a loss of bone density that increases the risk for fracture. In fact, the risk for osteoporosis may be higher with surgery than hormonal drugs.
Osteoporosis risk is higher with orchiectomy than with androgen suppressants. Some androgen suppressants, such as bicalutamide, may cause less bone loss. The use of estrogens may actually be bone protective. A number of medications are available to help prevent or reduce bone loss. Bisphosphonates are of particular note.
Complications of Androgen Deprivation. Men often experience fatigue, loss of energy, and emotional distress. 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 the following:
Side Effects. Side effects include hot flashes and occasionally nipple and breast tenderness.
Antiandrogens. Antiandrogens are powerful agents produced in the adrenal gland. They are used alone or in maximal androgen blockage (MAb), in which they are combined with LH-RH agonists or orchiectomy to completely block androgen hormones. Antiandrogens are either steroidal or nonsteroidal.
Nonsteroidal Antiandrogens. The nonsteroidal drugs are as follows: Flutamide (Eulexin, Drogenil). Flutamide has produced extended response in some patients. Interestingly, studies report that simple withdrawal produced a PSA decrease in about 20% of patients, which lasted between 3.5 and 5 months. Side effects reported with flutamide include diarrhea and liver damage, which has been fatalin 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 antiandrogens, including loss of sexual interest, osteoporosis, visual disturbance, and interstitial pneumonia. This agent is proving to have survival rates equal to those of maximal androgen blockage (MAb).• An interesting 2002 study suggested that flutamide may actually trigger a pathway that causes cell proliferation, which could be the reason why complete androgen blockage ultimately fails to prevent cancer progression. Steroidal Antiandrogens.
The steroidal antiandrogens act like female hormones and include the following: Megestrol Acetate. Megestrol acetate suppresses androgen production, but incompletely, and is generally not used as initial therapy.• Cyproterone Acetate. Cyproterone combined with estrogen may prevent the testosterone surge that occurs with LH-RH agonists.
Gonadotropin-Releasing Hormone (GnRH) Antagonists. Gonadotropin-releasing hormone (GnRH) stimulate the pituitary gland to release luteinizing hormone-releasing hormones (LH-RH). Drugs known as GnRH antagonists, such as abarelix (Plenaxis) and histrelin, block this action. They have two advantages over LH-RH agonists: They do not cause the same testosterone surge that can temporarily worsen cancer symptoms.• They seem to reduce testosterone levels more quickly.• In one study, histrelin was administered as an implant and was effective for up to 30 months. This offers an advantage over existing drugs, which must be administered at one to three -month intervals.
Estrogens. Estrogens, usually diethylstilbestrol (DES), may also be used. Certain types of these female hormones may exacerbate heart conditions in high doses, however, and their use has declined. Other estrogens, such as fosfestrole, may prove to be effective without posing such high risks. An estrogen agent, estramustine phosphate, which is also used in chemotherapy, is showing promise.
Aromatase Blockers. Aminoglutethimide (Cytadren) and similar drugs block aromatase, an enzyme important in estrogen production. Because the female hormone estrogen plays such a major role in the development of breast cancer, some experts postulate that blocking the small amount of estrogen found in men may also affect prostate cancer. Side effects include drowsiness and skin rash. Corticosteroids, such as prednisone, are important for reducing pain and improving quality of life. Some experts believe they should be the first choice for progressive prostate cancer that is resistant to hormonal treatments. Corticosteroids may be particularly effective in relieving pain and delay disease progression when used in combination with chemotherapy drugs, particularly mitoxantrone. There is evidence that corticosteroids can reduce PSA levels and boost survival in some patients.
•Vitamin-D Derived Treatments: Some studies are reporting that vitamin-D derived agents, such as calcitriol (Zemplar), may eventually be beneficial for prostate cancer patients. Calcitriol is derived from the active compound in vitamin D. It is being studied in combination with other chemotherapies. A 2003 study suggested that it may also enhance the treatment effects of radiation therapy without increase its adverse effects.
-- www.nci.nih.gov National Cancer Institute (800-422-6237)•
-- www.cancer.org American Cancer Society
• www.asco.org -- American Society of Clinical
www.4npcc.org -- National Prostate Cancer Coalition
Cancer Care, Inc. (800-813-HOPE)•
www.afud.org -- American Foundation for Urologic
www.nafc.org -- National Association for Continence
• www.simonfoundation.org -- The Simon
Foundation for Continence (800-23-SIMON)•
www.aicr.org -- American Institute for Cancer
www.duj.com -- Digital Urology Journal• www.jco.org --
The Journal of Clinical Oncology•
www.nccn.org -- National Comprehensive Cancer
www.psa-rising.com -- PSA Rising
www.centerwatch.com/studies/listing.htm -- Find clinical trials•
www.clinicaltrials.gov -- Find clinical
www.asco.org/people/db/html/m_db.htm -- Find an Oncologist•
-- www.cancer.org American Cancer Society (800-ACS-2345)
• www.asco.org -- American Society of Clinical Oncology (703-299-0150)•
www.4npcc.org -- National Prostate Cancer Coalition (888-245-9455)•
www.cancercare.org/index.asp -- Cancer Care, Inc. (800-813-HOPE)•
www.afud.org -- American Foundation for Urologic Disease (800-242-2383)•
www.nafc.org -- National Association for Continence (800-BLADDER)
• www.simonfoundation.org -- The Simon Foundation for Continence (800-23-SIMON)•
www.aicr.org -- American Institute for Cancer Research (800-843-8114)•
www.duj.com -- Digital Urology Journal• www.jco.org -- The Journal of Clinical Oncology•
www.nccn.org -- National Comprehensive Cancer Network•
www.psa-rising.com -- PSA Rising Magazine•
www.centerwatch.com/studies/listing.htm -- Find clinical trials•
www.clinicaltrials.gov -- Find clinical trials•
www.asco.org/people/db/html/m_db.htm -- Find an Oncologist•
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Stephen A. Cannistra, MD, Oncology, Associate Professor of Medicine,Harvard Medical School; Director, Gynecologic Medical Oncology, Beth Israel Deaconess Medical Center. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites.