Prostate Cancer

Prostate cancer is a malignant tumor that originates in the prostate gland and can eventually spread to other organs, bones, and tissues. The prostate is a cluster of small glands located beneath the bladder that surrounds the urethra, the tube that carries urine from the bladder out through the penis. Its principle function is to manufacture fluid that constitutes a portion of the semen.

Prostate cancer is the most common cancer in men in the United States and it is the second most common cause of cancer death in men over age 55. The incidence of prostate cancer increases dramatically with each decade after 50, and disease rates appear to vary by population. For example, North Americans (particularly African Americans) develop prostate cancer at one of the highest rates in the world, while Japan and Africa have low rates of the disease. Fortunately, prostate cancer tends to be slow-growing compared to many other cancers—the majority of prostate cancers either do not spread or cause harm for decades.

Signs and Symptoms

Many people with prostate cancer experience no symptoms at all.

Some symptoms that may indicate prostate cancer include:

• Difficult and painful urination
• Frequent urination and a feeling that one has to urinate even when the bladder is empty
• Incomplete emptying of the bladder, which may lead to dribbling of urine
• Awakening frequently in the night to urinate
• Decreased force of urine stream
• Blood in the urine
• Hip and back pain

When the cancer has spread to other parts of the body, symptoms can include:

• Bone pain
• Weakness or paralysis caused by compression of the spinal cord
• Weight loss
• Anemia
• Kidney failure

Causes

The causes of prostate cancer are unknown, but are thought to include environmental, nutritional, hormonal, and genetic factors. The influence of genes on the development of prostate cancer is suggested by the fact that prostate cancer tends to occur in men who are related to one another (see Risk Factors below); plus, a gene has been identified that is associated with 30% of family-related prostate cancers. Reports also indicate that farmers as well as men who work in tire, rubber, and sheet metal factories tend to have high rates of prostate cancer or more aggressive forms of the cancer. Some researchers speculate that environmental exposure to cadmium (present in commercial fungicides) and other harmful substances may be responsible for the high rates of prostate cancer in these men. Nutrition has been implicated in the development of prostate cancer because disease rates among men from countries with low prostate cancer rates (such as Japan) increase when they immigrate to the United States; this rise in incidence is thought to be due to the switch to a typical American diet, which is high in saturated fat. Elevated levels of male sex hormones, such as testosterone, may also play a role in the development of prostate cancer.

Risk Factors

The following factors may increase an individual's risk for prostate cancer:

• Older age—prostate cancer is most common among men who are older than 55
• Race—African Americans have a greater risk of developing prostate cancer than European Americans who, in turn, have a greater risk than Native and Hispanic Americans
• Family history of prostate cancer—having a brother with prostate cancer makes an individual 4.5 times more likely of developing the disease; having a father with prostate cancer makes an individual 2.3 times more likely of developing prostate cancer; having a sister or mother with ovarian or breast cancer is also considered a risk
• High-fat diet—foods rich in saturated fat may increase testosterone levels
• Lack of exercise may increase the risk in those who eat a high-fat diet
• Occupation—people who are regularly exposed to the chemicals dimethyl formamide and acrylonitrate, and the metal cadmium (such as metal workers and farmers) have high rates of prostate cancer

Diagnosis

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

• Digital rectal exam (DRE)—in this test, the physician inserts a gloved, lubricated finger into the patient's rectum in order to feel the prostate for bumps or other abnormalities. Many malignant tumors originate in the outer part of the prostate where they may be detected by this exam. Some men find this test embarrassing, but the DRE is quick and relatively painless, and helps detect 40% of all prostate cancers. Although as many as 40% of tumors identified using DRE have already spread outside of the prostate gland, studies indicate that regular DREs still save lives.
• PSA test—blood test measuring the level of prostate-specific antigen (PSA), a protein produced in the prostate gland that keeps semen in liquid form. Prostate cancer cells produce elevated quantities of PSA, so measuring PSA levels allows physicians to detect cancer while it is still microscopic. Unfortunately, the test is not accurate enough to definitively rule out or confirm cancer. For example, advancing age and benign conditions such as enlarged prostate can also elevate PSA levels. In general, PSA tests help detect up to 75% of all tumors.

If either the DRE or PSA test suggests the possible presence of cancer, the following tests will be performed to make a definite diagnosis:

• Transrectal Ultrasound—a visual image of the prostate is obtained by using ultrasound
• Biopsy of the prostate—a tissue sample is obtained through the rectum and examined for cancerous cells under the microscope

If the biopsy confirms the presence of cancer, several tests will be performed to detect any spread of the disease. This information gauges how serious the prostate cancer is at the time of diagnosis. Likely tests include the following:

• Imaging tests (CT and MRI)—computerized tomography (CT) or magnetic resonance imaging (MRI) scans may pinpoint the location of cancer that has spread beyond the prostate
• Bone scans and X rays—these look for spread of cancer to the bones
• Lymph node dissection—this is part of a surgical procedure to determine if the cancer has spread to the lymphatic system

Preventive Care

As described in the Diagnosis section, regular screening with the DRE and PSA exams by the doctor helps to detect prostate cancer in the early stages, before it has spread. Both the American Cancer Society and the American Urological Association recommend that men between the ages of 50 and 70 should have DRE or PSA tests performed annually. African American men or those with a family history of prostate cancer should begin screening at age 40.

Studies also suggest that the following lifestyle modifications may minimize the risk of prostate cancer:

• Consuming a low-fat diet, rich in fruits and vegetables
• Eating foods rich in selenium (such as brewer's yeast, wheat germ, chicken liver, nuts and seeds, tuna, herring, and oysters) and vitamin E (such as wheat germ, organ meats, sweet potatoes, leafy vegetables including spinach, nuts and seeds, eggs, soybeans, and lima beans)
• Exercising regularly, because exercise temporarily lowers testosterone

Treatment Approach

Treatment for prostate cancer depends on the stage of the disease, the age of the individual, the presence of other medical conditions, and the individual's preferences in conjunction with the physician's recommendations. If prostate cancer is detected early, treatment usually involves either surgical removal of the prostate or radiation therapy. For more advanced cases of prostate cancer, or if cancer spreads beyond the prostate, hormone medications are the preferred treatment. If the individual is older than 70 and has only a slow-growing tumor, the physician may adopt a strategy called "watchful waiting," in which the man returns frequently for check-ups and treatment only occurs if his condition worsens. During the time of watchful waiting (and also as a possible adjunct to surgery, medication, or radiation), dietary modifications may slow the growth of the cancer. For example, eating a low-fat diet, rich in fruits, vegetables, soy, selenium, and fiber has been associated with a decreased risk of prostate cancer. PC-SPES, an herbal mixture originating in Traditional Chinese Medicine, appears to significantly reduce PSA levels in people with prostate cancer. Acupuncture can relieve pain and the side effects of surgery while meditation and massage may reduce stress and anxiety associated with having prostate cancer.

Medications

Medications are considered the best therapy for people with advanced stages of prostate cancer or when cancer spreads from the prostate to other parts of the body. Drugs may also be prescribed prior to radiation therapy or when surgical procedures fail to lower PSA levels. Most medications for prostate cancer lower levels of male sex hormones (such as testosterone). Lowering testosterone levels can cause tumors to shrink or slow their growth.

Some commonly prescribed medications include:

• Luteinizing Hormone-Releasing Hormone (LH-RH) agonists (such as leuprolid, goserelin, and buserelin)—LH-RH is natural hormone, released by the hypothalmus in the brain, that lowers the production of testosterone; the medication encourages the release of this natural hormone. Side effects can include hot flashes, weight gain, development of male breast tissue, breast pain, and nausea.
• Hormones including antiandrogens (such as flutamide, bicalutamide, and nilutamide) and estrogens (such as diethylstilbestrol and ethinyl estradiol)—these medications reduce testosterone levels; side effects can include reduced sex drive, fatigue, nausea, impotence, diarrhea, and hot flashes
• Chemotherapeutic medications (such as vinblastine, mitoxantrone, and estramustine)—improve symptoms in advanced cancer but do not increase life expectancy
• Glucocorticoids—may be used along with chemotherapy to suppress production of male hormones

Surgery and Other Procedures

• Removal of the prostate (prostatectomy)—offers an excellent cure for men with prostate cancer that is completely confined to the prostate, and is performed if life expectancy is at least 10 years and cancer is confined to the prostate. Side effects include incontinence and impotence, but new procedures that spare nerves near the prostate preserve sexual function in 25% to 90% of men.
• Surgical exploration of lymph nodes—may be performed to evaluate whether prostate cancer has spread to the lymphatic system
• Resection of the prostate (called TURP or transurethral resection of the prostate)—removal of all or part of the prostate gland to eliminate cancer and to relieve obstruction of urine
• Removal of the testes (orchiectomy)—lowers testosterone levels; side effects can include impotence and hot flashes

In addition to these surgical procedures, radiation therapy may be effective for cancer confined to the prostate, particularly for older men. Radiation can be administered through an external source, or irradiated seeds can be placed internally near the prostate. Using irradiated seeds actually lowers the risk of damage to organs surrounding the prostate from radiation because administration can be more precise in both amount and location. Side effects can include proctitis (inflammation of the lining of the rectum), urinary tract infections, and impotence.

Nutrition and Dietary Supplements

Low-fat Diet
Population-based studies suggest that dietary fat may influence the risk of prostate cancer. In one study of 384 men with prostate cancer, those who consumed the most saturated fat (from, for example, meat, dairy, and butter) in the previous year were significantly more likely to develop advanced prostate cancer. Diets particularly high in animal fats have also been linked to an increased risk of prostate cancer among African Americans and to advanced stages of the disease in European Americans. While an association between high-fat diets and prostate cancer is not definitive, it is probably wise for people at risk for prostate cancer to avoid foods high in saturated fat and trans fatty acids (such as margarine).

Fruits and Vegetables
People who consume higher amounts of fruits and vegetables, especially cruciferous vegetables (such as broccoli, cauliflower and Brussels sprouts) may have a reduced risk of developing prostate cancer. One study of more than 1,200 men (half with prostate cancer and half free of the disease) found that those who consumed 28 or more servings of vegetables per week were 35% less likely to develop prostate cancer than those who had less than 14 servings per week. Although this type of study cannot be considered definitive, eating at least four servings of vegetables per day to help prevent or slow the progression of the disease is reasonable and may be healthy for a variety of reasons.

Fructose, or fruit sugar, seems to stimulate the production of a certain form of vitamin D (see below) which, in turn, has been associated with a decreased risk of advanced prostate cancer. As with vegetables, therefore, including fruit in the diet also appears to be safe and potentially beneficial.

Omega-3 Fatty Acids
Laboratory and animal studies indicate that omega-3 fatty acids (specifically, docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) may inhibit the growth of prostate cancer. Similarly, population based studies of groups of men suggest that a low-fat diet with the addition of omega-3 fatty acids from fish or fish oil help prevent the development of prostate cancer. A healthy balance of omega-3 to omega-6 fatty acids appears to be particularly important for reducing the risk of this condition. Alpha linolenic acid (ALA; another omega-3 fatty acid) may not offer the same benefits as EPA and DHA. In fact, one recent study evaluating 67 men with prostate cancer found that they had higher levels of ALA compared to men without prostate cancer. More research in this area is needed.

Lycopene
While some studies suggest that lycopene, the primary ingredient in tomatoes, may protect against prostate cancer, this relationship is not entirely clear. Lycopene is a carotenoid that acts as an antioxidant, protecting cells from damage that may become cancerous over a long period of time. In a large study, lycopene levels were significantly lower in those with prostate cancer compared to those without. However, tomato consumption in another study did not reduce the risk of prostate cancer. Although levels of this carotenoid in the blood may be lower in those with prostate cancer, eating more tomatoes in order to raise lycopene levels may not make a difference in the risk of development or treatment of prostate cancer. Like other vegetables, however, it seems safe and reasonable to include tomatoes in the diet.

Soy
People who live in cultures in which soy is a large part of the diet are at less risk for developing hormone-related cancers, such as prostate cancer. For example, men living in Japan have a significantly lower risk of developing prostate cancer than men in the United States—notably, the Asian diet contains significantly more soy than the typical American diet. Laboratory and animal studies also suggest that genistein, a plant based hormone (phytoestrogen) which comes from soy, may suppress the growth of prostate cancer cells. Such studies are promising, but the role of soy in preventing or treating prostate cancer in people remains unclear.

Selenium
Several studies indicate that selenium, an antioxidant, may protect against prostate cancer. In one large study, 1,312 people with skin cancer—three quarters of them men—received either 200 micrograms of selenium (in the form of brewer's yeast) or a placebo for approximately 4 years. Study participants were followed for over 6 years. Men who received selenium were significantly less likely to develop prostate cancer by the end of the study than men who received placebo. Laboratory studies also suggest that selenium may suppress the growth of prostate cancer cells. Selenium supplementation may be worth considering as part of a regimen to treat or prevent progression of prostate cancer.

Beta-Carotene
Beta-carotene is an antioxidant that occurs naturally in the body. In a well-respected long-term study, supplementing with beta-carotene appeared to reduce the risk of developing prostate cancer by 32% in men who had low levels at the beginning of the study. However, because other large trials have not shown it to be useful in preventing prostate cancer, the benefits of beta-carotene are still unclear. More information is needed before recommendations for beta-carotene can be made, particularly because supplementation with these antioxidants has been associated with increased risk of certain types of cancer.

Vitamin E
One recent study found that a form of vitamin E found in soybean oil, known as gamma-tocopherol, may significantly decrease the risk of prostate cancer. Researchers measured levels of gamma tocopherol, selenium, and alpha-tocopherol (another form of vitamin E), in the blood and toenails of 117 men with prostate cancer and 233 healthy men. Men with the highest levels of gamma tocopherol were significantly less likely to develop prostate cancer compared to those with the lowest levels.

Vitamin D
Laboratory and animal studies have suggested that a certain form of vitamin D, known as 1, 25 dihydroxy vitamin D, inhibits growth of prostate cancer cells. What this means for people with or at high risk for prostate cancer is unclear. Some experts suggest eating several servings of fruit daily, which helps stimulate production of this form of vitamin D, and avoiding dairy, which may inhibit production of this type of vitamin D. This latter suggestion, however, is somewhat controversial and not scientifically proven at this time.

Fiber
In one 4-month, randomized, controlled trial studying men with high cholesterol, researchers happened to note that PSA levels were lowered after the men consumed meals high in soluble fiber (such as barley, peas, beans, oat bran, and cereal with psyllium) but not with meals rich in insoluble fiber (such as wheat bran cereal as well as high-fiber crackers and bread). However, these findings do not necessarily indicate that a diet high in fiber will lower PSA readings, or guarantee a decreased risk for prostate cancer.

Melatonin
Studies suggest that melatonin levels are lower in people with prostate cancer than those without cancer. In addition, men with prostate cancer also tend to have lower than normal nighttime levels of this hormone. In one study, melatonin (when used in conjunction with conventional medical treatment) improved survival rates in 9 out of 14 patients with metastatic prostate cancer. Laboratory studies have also found that melatonin inhibits the growth of prostate cancer cells in test tubes. Interestingly, meditation is thought to be a valuable addition to the treatment of prostate cancer as it has been shown to increase levels of melatonin in the body. Although these early results are intriguing, more research is needed.

Quercetin
Preliminary laboratory studies suggest that the flavonoid quercetin inhibits prostate cancer cells in test tubes. How this will ultimately translate to prevention or treatment of prostate cancer in men is unknown at this time.

Herbs

Red Clover (Trifolium pratense)
In one report, a 66 year old man who took red clover every day for a week prior to having a prostatectomy for prostate cancer showed reduced signs of cancer in the diseased prostate tissue. While making any assumptions from one case report is highly speculative, the authors of the report hypothesize that plant estrogens (phytoestrogens) in the red clover may have been responsible for the observed improvement. It may be worthwhile to test this theory in a large number of people with prostate cancer over an extended period of time.

St. John's wort (Hypericum perforatum) and kava kava (Piper methysticum)
At least 25% of people with advanced prostate cancer are depressed, and many are anxious. Some experts recommend St. John's wort to help alleviate depression or kava kava to soothe anxiety. Use of these herbs should be discussed with your healthcare provider, who can also describe the potential for interactions between the herbs and prescription medications. For example, St. John's wort should not be taken with other antidepressants or with a class of drugs called protease inhibitors (used for HIV).

Ginkgo (Ginkgo biloba)
While ginkgo has become a popular remedy for men who are unable to have an erection (a side effect of many prostate cancer treatments), the herb has not been specifically studied for this use in men with prostate cancer.

Acupuncture

Acupuncture may provide relief from side effects of orchiectomy (removal of the testes). In one small trial, 4 out of 6 men who were given acupuncture twice weekly for 2 weeks and then once a week for 10 weeks reported a decreased number of hot flashes. Studies also support the use of acupuncture for the pain that often occurs when cancer has spread beyond the prostate (particularly to the bones). A National Institutes of Health statement released in 1997 also supports the use of acupuncture to alleviate nausea associated with chemotherapy.

While acupuncture is not used as a treatment for cancer itself, evidence suggests it can be a valuable therapy for cancer-related symptoms (particularly nausea and vomiting that often accompanies chemotherapy treatment). There have also been studies indicating that acupuncture may help reduce pain and shortness of breath. Acupressure (pressing on rather than needling acupuncture points) has also proved useful in controlling breathlessness; this is a technique that patients can learn and then use to treat themselves.

Some acupuncturists prefer to work with a patient only after the completion of conventional medical cancer therapy. Others will provide acupuncture and/or herbal therapy during active chemotherapy or radiation. Acupuncturists treat cancer patients based on an individualized assessment of the excesses and deficiencies of qi located in various meridians. In many cases of cancer-related symptoms, a qi deficiency is usually detected in the spleen or kidney meridians.

Massage and Physical Therapy

Studies suggest that massage reduces stress and boosts immune function, so it may help relieve anxiety for men undergoing treatment for prostate cancer.

Pelvic floor exercises—the repetitive use of muscles that start and stop the flow of urine—may help decrease incontinence caused by prostatectomy (removal of the prostate). This therapeutic approach is often combined with biofeedback.

Mind/Body Medicine

Meditation
Meditation may benefit men with prostate cancer by helping them to reduce stress, ease anxiety, and regain a sense of self-control.

Biofeedback and Pelvic Muscle Training (PMT)
Several studies have found that learning to start and stop the flow of urine by repeatedly using the muscles of the pelvis (PMT) in combination with biofeedback can reduce the duration of incontinence after prostate cancer surgery. Other studies suggest however, that PMT alone, with or without biofeedback, is responsible for the beneficial effects. Either way, both PMT and biofeedback are safe, noninvasive therapies that may benefit men who suffer from incontinence following either surgical removal of the prostate or other treatments for prostate cancer.

Traditional Chinese Medicine

PC-SPES
Several studies suggest that the traditional Chinese herbal mixture, PC-SPES, appears to be a promising treatment for prostate cancer. As suggested by a recent study of 67 men with prostate cancer at the Memorial Sloan-Kettering Cancer Center, PC-SPES, a combination formula containing the following herbs may reduce PSA levels in men with prostate cancer:

• Chrysanthemum (Dendrantherma morifolium)
• Reishi mushroom (Ganoderma lucidium)
• Licorice (Glycyrrhiza glabra)
• Da Qing Ye (Isatis indigotica)
• San-qi ginseng (Panax pseudo-ginseng, Wall)
• Chinese skullcap (Sculletaria baicalensis, Georgi)
• Saw palmetto berry (Serenoa repens)

While these results are promising, further studies are needed to determine whether PC-SPES is safe and effective for men with prostate cancer. In fact, a well-designed long-term study is currently underway by researchers at the University of California, San Francisco in collaboration with scientists at the Dana Farber Cancer Institute in Boston. Research regarding possible use of PC-SPES is of particular interest for men who do not respond to surgery, radiation, or medication. Commonly reported side effects of PC-SPES include loss of libido, impotence, leg cramps, diarrhea, and hot flashes. More serious side effects have included blood clots, allergic reactions, and heart and kidney failure.

Other Considerations

Prognosis and Complications
Most complications from prostate cancer result from specific treatments. These include:

• Prostatectomy—can cause incontinence and/or impotence
• Radiation therapy—can cause proctitis (inflammation of the lining of the rectum), bladder infections, and/or impotence
• Hormone medications—can cause loss of libido, impotence, hot flashes, excessive development of male breasts, and tenderness in male breast tissue
• Removal of testes—can cause impotence and hot flashes

The outlook for a man with prostate cancer depends on his age, the stage of tumor growth, whether he has any underlying medical illnesses, and his PSA levels. The prognosis for men with cancer that has not spread beyond the prostate is quite good. Most of these cancers are curable with appropriate treatment, and after 15 years the same number of these men will be alive as those who never had prostate cancer. If the cancer spreads beyond the prostate and does not respond to hormone medications, however, there is little hope for a cure. Still, prostate tumors are slow-growing, and even men with advanced prostate cancer can survive for 5 years or more.

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