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An in-depth report on the causes, diagnosis, treatment, and prevention of prostate cancer.

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.]

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

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.

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The findings, say researchers, suggest that many family caregivers need help
as well — for the sake of their own health and that of the cancer patient.

Of the 60 female caregivers in the study:

1. 40 percent had significant anxiety symptoms
2. 12 percent were suffering from depression
3. About one-third reported substantial fatigue or sleep disturbances; and 
4. Another 15 percent complained of bodily pain

The women, mostly wives, were 64 years old, on average, and their rates of
each of these conditions surpassed the average for U.S. women their age, the
researchers point out.

Experts at the American Institute for Cancer Research (AICR) recently reported that whole foods, not dietary supplements, play a role in lowering cancer risk. Citing a huge and comprehensive AICR report on cancer prevention, the panel of experts cautioned against relying on pills and powders as a means of protection.

“When the panel examined the accumulated evidence from almost 50 different supplement trials, cohort studies and case-control studies, the results were simply too inconsistent to justify using supplements to protect against cancer,” said AICR Nutrition Advisor Karen Collins, MS, RD.

The panel also reported that under certain conditions, some high-dose supplements seemed protective at specific doses, some did nothing, and some actually increased the risk of cancer.

“Let’s be clear: although some people have misread the recommendation as simply, ‘Don’t take supplements ever,’ that’s not what the expert panel concluded,” said Collins. “The panel members were careful to make an important distinction, namely: Don’t rely on supplements to protect you from cancer.”

Different Grades for Different Cancer Links

Of all the supplements reviewed by the panel, only two seemed to have a potential role in protection, and even then the research was less than clear.

*According to the panel, selenium probably protects against prostate cancer, while calcium probably protects against colorectal cancer. Yet they also concluded that high calcium consumption probably increases risk for prostate cancer.*

Whole Foods vs. Supplements

The data on prevention are considerably more consistent, however, when it comes to foods that contain many of the same vitamins, minerals and other substances that are often sold in supplement form. The panel judged the evidence on several categories of such foods as protective against a variety of cancers, including:

* Foods containing lycopene are probably protective against prostate cancer.
* Foods containing selenium are probably protective against prostate cancer.

That said, no matter how you say it, “to-may-to” or “to-mah-to,” it’s good for you.  Have a pizza.

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The findings, which appear in today’s issue of Clinical Cancer Research, reaffirm that patients should inform their doctors about any herbal or hormonal dietary supplements they are taking or considering taking. The researchers also recommend that documentation of supplement usage become part of routine health assessments for all patients, particularly cancer patients.

“Physicians need to ask their patients not only about the prescription drugs they may be taking, but – perhaps even more importantly – about the over-the-counter drugs and supplements, which may have a profound impact on certain health conditions,” said Dr. Claus Roehrborn, chairman of urology at UT Southwestern and one of the study’s authors.

The researchers began their investigation when two patients being seen by UT Southwestern doctors developed aggressive prostate cancer within months of starting daily consumption of the same dietary supplement. Both men purchased the same product, one to develop stronger muscles and enhance sexual performance, the other to gain muscle.

Dr. Roehrborn, Dr. Shahrokh Shariat, a resident in urology and the study’s lead author, and their colleagues analyzed the supplement, which is not named in the study. They found that the product’s label listed ingredients that were not present, misrepresented the concentrations of the ingredients present and failed to list all the steroid hormones contained in the product.

Hormone analysis revealed that the supplement contained testosterone and estradiol, a sex hormone. Researchers then tested the effect of the product on human prostate cancer-cell lines. The product proved to be a more potent stimulator of cancer-cell growth than testosterone. Additionally, attempts to stop the cancer-cell growth with increasing concentrations of the anti-cancer drug bicalutamide proved to be futile.

“Bicalutamide is an oral nonsteroidal anti-androgen used to treat prostate cancer,” Dr. Shariat said. “The fact that this supplement caused the drug to be less effective is very troubling.”

Based on the clinical data and cell culture experiments, the researchers filed an adverse event report with the Food and Drug Administration. The government agency in turn issued a warning letter to the manufacturers, which led to the removal of the product from the market.

“Unlike prescription and over-the-counter drugs, the law does not require nutritional supplements to undergo pre-market approval for safety and efficacy,” Dr. Shariat said. “The current FDA regulatory system provides little oversight or assurances that dietary supplements will have predictable pharmacological effects or even that product labels provide accurate information for consumers.”

The researchers say expanded research is needed to define the mechanism, safety and efficacy of common herbal and hormone dietary supplements.

“For most supplements efficacy is not established in randomized, controlled trials. What is worse, safety is often equally poorly established,” said Dr. Roehrborn, who directs the Sarah M. and Charles E. Seay Center for Pediatric Urology.

An estimated 42 percent to 69 percent of U.S. adults use dietary supplements, at an estimated out-of-pocket expenditure of about $34.4 billion, according to published reports cited in the study. Individuals often use supplements because they believe these natural products are safe and drug-free. The sale of androgenic steroids is exponentially increasing. In 2004, U.S. expenditures on testosterone supplements were estimated to be $425 million.

“Given that testosterone supplements are in high demand, there is significant concern that supplements, in addition to the one we evaluated, may pose an urgent human health risk,” Dr. Shariat said.

Researchers from Baylor College of Medicine in Houston also contributed to the research.

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In addition, the researchers, led by Marja Nevalainen, M.D., Ph.D., associate professor of Cancer Biology at Jefferson Medical College of Thomas Jefferson University, also showed that the convergence of two biological pathways could be responsible for making such hormone-resistant prostate cancers especially dangerous. They have found that a synergy between Stat5 and hormone receptors in recurrent prostate cancer cells helps each maintain its activity. Dr. Nevalainen and her co-workers report their findings January 1, 2008 in the journal Cancer Research.

“These findings validate Stat5 as a potential drug target in prostate cancer, and in particular, in a form of prostate cancer for which there are no effective therapies,” Dr. Nevalainen says.

Men with primary prostate cancer usually have either surgery or radiation, whereas subsequent disease is frequently treated by hormone therapy. But if the cancer recurs again, years later, it can be more aggressive and typically fails to respond to hormone treatment. In previous work, the researchers showed that when Stat5 is turned on in primary prostate cancer, men are more likely to have recurrent disease.

In the current study, the team examined human prostate cancer cells of 198 patients with prostate cancer recurrence. They found that Stat5 was active in 74 percent of all recurrent prostate cancers. Of these patients, 127 had been treated with androgen deprivation therapy. The researchers found Stat5 was active in 95 percent of these hormone resistant tumors, meaning it was more likely to be active if the patient had been treated with hormone deprivation therapy.

Dr. Nevalainen shows that Stat5 interacts with the androgen receptors and keeps them “transcriptionally active.” Next, the scientists would like to conduct tests in animal models to see if this synergy promotes androgen-independent prostate tumor growth, and whether or not Stat5 synergizes with androgen receptors activated by adrenal androgens, which are present in the absence of testicular androgens during the hormone therapy of prostate cancer in patients.

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When we take any test, it is preferable to get a definite answer: “yes, you have the cancer” or “no, you don’t”. Unfortunately the PSA test is not that good. At best, it is an indicator of the probability or risk that you have prostate cancer. This can be very helpful, because it guides the decision about whether you should have further tests. However it does mean that the interpretation of PSA levels is not necessarily straight forward.

What conditions other than cancer cause the PSA level to rise?

The prostate typically enlarges as men grow older, and because small amounts of PSA are produced by the healthy prostate, its blood level tends to rise. Benign prostate enlargement (a condition which causes urinary symptoms such as poor flow, getting up at night), is a common non-cancer condition causing PSA levels to rise. For this reason, age-based thresholds, shown in Table 1, can be used to decide if a test result is abnormal. The percentage Free to Total PSA (described below) also gives an indication whether raised PSA is due to benign enlargement.

A temporary rise in the PSA can be caused by a number of conditions ¹. Urinary infection, prostatitis (inflammation of the prostate), or a biopsy of the prostate can cause large rises while small rises can be caused by ejaculation and even bicycle riding. Because of these non-cancer causes of PSA rises, it is not surprising that if you have an abnormally high test result, it may not be due to prostate cancer. The chance that you have prostate cancer is only about one in three.

Note: These levels are used only as a guide. It is possible to have prostate cancer and have a PSA level in the normal range, although this is uncommon.

If, in addition to the PSA test, you have a rectal examination, and it also is abnormal, your chances of having prostate cancer are higher, (one in two).

Other ways of measuring PSA have been developed in an effort to make the test more specific for prostate cancer. One of these is called the “Free to Total” PSA. This is a ratio, expressed as a percent. Much of the PSA in the blood is bound to protein, including that produced by cancer cells. But men with benign prostate enlargement have higher levels of free (unbound) PSA and so a higher Free to Total ratio. If the total PSA level is abnormal, the Free to Total PSA ratio will give an idea of whether the rise is due to benign disease or cancer. Cancer is more likely if the Free to Total percentage is below 10% ². This test is available and widely used throughout Australia.

What is a normal PSA level?

Most authorities agree that if you have a PSA greater than 4 ng/ml, you should have further investigations. Some suggest that if your PSA is greater than the ‘normal for age’ range shown in Table 1, or if it is rising rapidly, it should be investigated.

Depending on your age and family history, your doctor may then refer you directly to a Urologist, or may repeat the test before referring you for further investigation.

If cancer is present, the level of PSA in the blood rises as the tumour grows. This means that small rises in PSA are found in association with small tumours which may be still confined to the prostate gland (localised). PSA levels of 10ng/ml or less have the best chance of being localised ³. The PSA level and the cancerous characteristics of the tumour cells themselves (called “grade”) can indicate the risk that a tumour has grown beyond the prostate.

If cancer is present, the rate at which the PSA level increases over a series of tests (called PSA velocity) also gives information about the risk that cancer will recur after treatment.

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See your health care provider if you have any of the following symptoms:

       Difficulty initiating and/or stopping a urine stream

       Frequent urination

       Pain on urination

       Pain on ejaculation

You should undergo regular screening for prostate cancer.

       Men aged 50 years and older should undergo a yearly digital rectal examination and blood testing for prostatic specific antigen (PSA).

       Men in the high-risk group, such as those with a family history of prostate cancer or of African American ethnicity, should begin screening as early as age 40 years.

Go to the nearest hospital emergency department right away if you have any of the following symptoms:

       Urinary tract infection - Burning pain on urination, urgency, frequent urination, especially with fever

       Bladder obstruction - Not urinating or urinating very little despite drinking enough fluid; producing little urine despite straining; pain due to a full bladder

       Acute- Not urinating or urinating little, with little discomfort, despite drinking enough fluid

       Deep bone pain, especially in the back, hips, or thighs, or bone fracture - Possible sign of advanced prostate cancer that has spread to the bones

Spinal cord compression is a true emergency and may be the first sign of cancer. It occurs when the cancer has spread to vertebrae of the spine and tailbone region. The weakened vertebrae can collapse on the spinal cord, causing symptoms and problems with function.

       Symptoms depend on the level at which the spine is compressed.

       Typical symptoms that might signal acute spinal cord compression include weakness in the legs and difficulty walking, increased difficulty urinating or moving your bowels, difficulty controlling your bladder or bowels, and decreased sensation, numbness, or tingling in the groin or legs.

       These are often preceded by pain in the hip (usually one sided) or back lasting a few days or weeks.

       Such symptoms require immediate evaluation in the nearest hospital emergency department. Failure to be treated immediately can result in permanent spinal cord damage.

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Brachytherapy is often referred as “prostate seed therapy”, and describes the procedure where a radioactive material is inserted into the prostate often directly into the tumors. The radiation from these “seeds” often cause the tumors to shrink and die. Brachytherapy is quite common and has been used in the US since the late 80s.

There are two types of brachytherapy treatment: High Dose Rate (HDR), and Low Dose Rate (LDR). LDR brachytherapy is the most commonly used of the two.

Low Dose Rate (LDR) Brachytherapy

LDR Brachytherapy involves low dose radioactive “seeds” being permanently implanted into the prostate. The “seeds” are smaller than grains of rice, and radiation from the seeds wear off after several months. The intended result is a destroyed tumor in the area where a seed has been placed.

LDR Brachytherapy is performed under anesthesia, and radioactive “seeds” are each placed in needles that are inserted into the target through the perineum (the area between the legs, scrotum and anus). Once at the target, the seed is left and the needle is withdrawn. This procedure is repeated until all of the seeds are placed at their targets.

There are few long term risks associated with LDR brachytherapy treament.

High Dose Rate (HDR) Brachytherapy

HDR Brachytherapy utilizes a highly radioactive source that is placed temporarily into the affected areas of the prostate. This high intensity radiation is timed over a period of minutes and often repeated two or three times over several days.

HDR Brachytherapy is performed under anesthesia, and catheters (hollow plastic tubes) are placed through the perineum to give access to the target areas. A remote device is used to place the radioactive material at the target for the intended period of time and then withdraw it. The catheters stay in place over the next few days during the repeated treatments. The patient is then awakened and returned to their room.

Brachytherapy Side Effects

Urinary irritation is a very common side effect of brachytherapy. The urine stream becomes blocked by the swollen prostate about 5-15 percent of the time, and a foley catheter is placed to allow urine flow. Obstruction usually subsides after several weeks allowing removal of the catheter.

Bowel side effects (like diarrhea and cramping) are relatively uncommon with brachytherapy. Erectile dysfunction is always a concern with radiation treatments.

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The prostate is a walnut-sized gland located just below the bladder in men. It surrounds the top portion of the male urethra (the tube that transports urine and semen out of the body). The gland’s main function is to produce semen (a thick fluid that nourishes and transports sperm). Prostate cancer (an abnormal, uncontrolled growth of cells originating in the prostate gland) is the most common cancer, and the third-leading cause of cancer deaths, among American men. About 1 man in 6 will be diagnosed with prostate cancer during his lifetime. Although about 80% of men who reach age 80 are found to have prostate cancer, this condition alone may not contribute to serious harm if it does not spread. The November 15, 2006, theme issue of JAMA on men’s health includes several articles dealing with prostate cancer.

DIAGNOSTIC TESTING FOR PROSTATE CANCER

Doctors and medical groups do not agree on when men should be screened (routinely tested) for prostate cancer because of controversy about the benefits vs risks of early treatment. The most often used screening tests include

• Digital rectal examination (DRE)—A doctor feels the prostate gland by passing a gloved finger into the patient’s rectum to find hard or lumpy areas of the gland, which may represent an abnormality.
• Blood test (to detect a substance called PSA, prostate-specific antigen)—It is important to understand that the test is not perfect. Many men with mildly elevated PSA levels can have noncancerous prostate enlargement, which is a normal part of aging, whereas men with prostate cancer may have normal levels of PSA.

Prostate cancer is a very individual-specific disease. Discussions between the patient and his doctor are important to decide about testing and treatment. Based on an individual’s situation, additional tests may be considered.

INITIAL TREATMENT OPTIONS

Decisions regarding the best treatment for you depend on a number of factors. These include your age, life expectancy, overall health status, and the growth and spread of the tumor, along with your doctor’s recommendations.

• Watchful waiting (expectant management)—Conservative care involves watching for new signs or symptoms with regular checkups and testing.
• Surgery—The most effective way to cure prostate cancer is to undergo a radical prostatectomy (removal of the prostate gland). This treatment can result in subsequent problems regarding impotency (difficulty having an erection) or incontinence (problems with control of urination).
• Radiation therapy (treatment with high-energy x-rays to kill or shrink cancer cells)—There are 2 types of therapeutic approaches: external beam (radiation comes from outside the body) and brachytherapy (internal radiation from radioactive materials placed directly into the prostate).

 INFORM YOURSELF

Sources: American Cancer Society, American Association of Clinical Urologists, American Urological Association

The JAMA Patient Page is a public service of JAMA. The information and recommendations appearing on this page are appropriate in most instances, but they are not a substitute for medical diagnosis. For specific information concerning your personal medical condition, JAMA suggests that you consult your physician. This page may be photocopied noncommercially by physicians and other health care professionals to share with patients. To purchase bulk reprints, call 203/259-8724.

TOPIC: CANCER

John L. Zeller, MD, PhD, Writer; Cassio Lynm, MA, Illustrator; Richard M. Glass, MD, Editor

JAMA. 2006;296:2402.

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The prostate is a small organ about the size of a walnut. It is found below the bladder (where urine is stored) and surrounds the tube that carries urine away from the bladder (urethra). The prostate makes a fluid that becomes part of semen. Semen is the white fluid that contains sperm.

Prostate problems are common in men age 50 and older. Sometimes men feel symptoms themselves, or sometimes their doctors find prostate problems during routine exams. Doctors who are experts in diseases of the urinary tract (urologists) diagnose and treat prostate problems.

There are many different kinds of prostate problems. Many don’t involve cancer, but some do. Treatments vary but prostate problems can often be treated without affecting sexual function.

Common Problems

There are several common prostate problems including: 

Acute prostatitis

Acute prostatitis is an infection of the prostate caused by bacteria. It usually starts fast and can cause fever, chills, or pain in the lower back and between the legs. It also can cause pain when you urinate. If you have these symptoms, see your doctor right away. Antibiotic drugs usually help heal the infection and relieve the symptoms. Your doctor also may suggest that you drink more liquids.

Common Problems

There are several common prostate problems including: 

Acute prostatitis

Acute prostatitis is an infection of the prostate caused by bacteria. It usually starts fast and can cause fever, chills, or pain in the lower back and between the legs. It also can cause pain when you urinate. If you have these symptoms, see your doctor right away. Antibiotic drugs usually help heal the infection and relieve the symptoms. Your doctor also may suggest that you drink more liquids.

Chronic prostatitis

Chronic prostatitis is a prostate infection that keeps coming back time after time. Symptoms may be milder than in acute prostatitis, but they can last longer. Chronic prostatitis can be hard to treat. Antibiotics may work if bacteria are causing the infection. But if bacteria are not the cause, antibiotics won’t work. Massaging the prostate sometimes helps to release fluids. Warm baths also may bring relief. Often chronic prostatitis clears up by itself.

Benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is the term used to describe an enlarged prostate. BPH is common in older men. Over time, an enlarged prostate may block the urethra, making it hard to urinate. It may cause dribbling after you urinate or a frequent urge to urinate, especially at night. Your doctor will conduct a rectal exam to diagnose BPH. The doctor also may look at your urethra, prostate, and bladder. 

Treatment choices for BPH include:

• Watchful waiting. If your symptoms are not troubling, your doctor may suggest that you
  wait before starting any treatment. In that case, you will need regular checkups to make sure the condition does not get worse.
• Alpha-blockers (some generic names are doxasozin, terazosin) are medicines that can relax muscles near the prostate and ease symptoms. Side effects may include headaches, dizziness, or feeling lightheaded or tired.
• Finasteride (Proscar) acts on the male hormone (testosterone) to shrink the prostate. Side effects of this medication can include less interest in sex and problems with erection or ejaculation. 
• Surgery also can relieve symptoms. But surgery can cause complications. Also, it does not protect against prostate cancer.

Talk with your doctor about this treatment choice. Regular checkups are important even for men who have had BPH surgery.

There are three kinds of surgery:

• Transurethral resection of the prostate (TURP) is the most common type of surgery. While the patient is under anesthesia, the doctor uses a special device to take out part of the prostate and remove the blockage.
• Transurethral incision of the prostate (TUIP) may be used when the prostate is not too enlarged. The doctor makes a few small cuts in the prostate near the opening of the bladder. This relaxes the bladder muscles and improves the flow of urine.
• Open surgery is used when the prostate is very enlarged. In this process, prostate tissue is removed directly rather than through the urethra.

Prostate Cancer

Prostate cancer is one of the most common types of cancer among American men. It is more common among African American men than white men. Treatment for prostate cancer works best when the disease is found early.

Diagnosing Prostate Cancer

Doctors will ask questions about your medical history and perform a physical exam to find the cause of prostate problems. In the exam, the doctor feels the prostate through the rectal wall. Hard or lumpy areas may mean that cancer is present. 

Your doctor also may suggest a blood test to check your prostate specific antigen (PSA) level. PSA levels may be high in men who have an enlarged prostate gland or prostate cancer. PSA tests are very useful for early cancer diagnosis. But PSA test results alone do not always tell whether or not cancer is present. 

When doctors suspect cancer, they also may perform a biopsy. Using this simple method, doctors can take out a small piece of the prostate and look at it under a microscope.

Prostate Cancer Treatment

There are many options for treating prostate cancer. Each treatment plan is based on details, such as whether or not the cancer has spread beyond the prostate (stage of cancer), your age and general health, and how you feel about the treatment options and side effects. Some of the treatment choices include:

• Watchful waiting, as with BPH, if the cancer is slow growing and not causing problems, you may decide not to have treatment right away. Instead, your doctor will watch closely for changes in your condition. Men who are older or have another serious illness often choose this option. 
• Surgery is used to take out the cancer. Among the different types of surgery for prostate cancer are:
  • Radical prostatectomy. This surgery takes out the entire prostate and nearby tissues. Side effects may include lack of sexual function (impotence) or problems holding urine (incontinence). Improvements in surgery now make it possible for some men to keep their sexual function. Some men with trouble holding urine may regain control within several weeks of surgery. Others continue to have problems that require them to wear a pad.
  • Cryosurgery kills the cancer by freezing it. 
• Radiation therapy uses high-energy X-rays to kill cancer cells and shrink tumors. Radiation therapy sometimes is beamed into the prostate from outside the body. It can cause problems with impotence and bowel function.
  • Brachytherapy is a type of radiation therapy often used when the cancer is found only in the prostate gland. It also is sometimes called internal radiation, implant radiation, or interstitial radiation therapy. In this treatment, the doctor places radioactive “seeds” directly into the prostate. This focuses the radiation directly on the cancer and lowers the chance of affecting other, healthy areas around the prostate.
• Hormone therapy stops cancer cells from growing. The growth of prostate cancer often depends on testosterone. Drug treatment is one effective way to block testosterone. This treatment is often used for prostate cancer that has spread to other parts of the body. 

You can get more detailed information on the pros and cons of these treatment choices by calling the National Cancer Institute’s Cancer Information Service at 1-800-422-6237. Ask for prostate cancer information in “PDQ for Patients.”

Protecting Yourself

These are the signs of prostate problems: 

• Frequent urge to urinate
• Blood in urine or semen
• Painful or burning urination
• Difficulty in urinating
• Difficulty in having an erection
• Painful ejaculation
• Frequent pain or stiffness in lower back, hips or upper thighs
• Inability to urinate
• Dribbling of urine

If you have any of these symptoms, see your doctor right away to find out if you need treatment.

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MANCHESTER, UNITED KINGDOM. Men face a much more dangerous form of prostate cancer if tumor cells from the prostate gland metastasize and migrate and invade other parts of the body, such as bone marrow. New research suggests that oily fish may help prevent this process. It appears that omega-3 fats contained in oily fish can prevent the cancer spreading to bone marrow, a process which may be encouraged by the other major group of polyunsaturated fatty acids – omega-6 fats. Researchers at the Christie Hospital in Manchester found evidence for this effect in laboratory tests, where they showed that omega-3 fats can inhibit invasion by prostate cancer cells, potentially reducing the threat of metastasis. They also found that omega-6 fatty acids, found in vegetable oils, nuts and seeds, increased the risk of tumor cells spreading into bone marrow. This invasion was blocked by omega-3 fats, which are found in oily fish such as salmon, mackerel and tuna. The researchers believe that cancerous tumors may use omega 6 fats as a high-energy food, enabling rapid growth. Omega-3 fats are known to interfere with the various functions of omega-6 fats, they explain, and this was confirmed by the current findings. This effectively removes the cancer’s ‘free lunch’, a fact that may have clinical importance. Eating a diet with the right balance of omega-3 and omega-6 fats may well help to keep prostate cancer within the prostate gland where it may be monitored safely or more easily treated with surgery or radiotherapy, they conclude, adding that a healthy balance of these two types of fat would be about half as much omega-3 as omega-6. Many cancers, including breast and prostate cancer, seem to invade bone marrow rather than other parts of the body. If it could be shown that this is influenced by the proportion of different types of fat, then scientists may be able to develop drugs that prevent metastasis.
Brown, M.D. et al. Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs. British Journal of Cancer, Vol. 94, March 27, 2006. pp. 842-53

Design of the SELECT trial
HOUSTON, TEXAS. It is estimated that 230,000 American men will be diagnosed with prostate cancer and that 30,000 men will die from the disease in 2004. There are currently no pharmaceutical drugs that have been proven effective in preventing prostate cancer. Finasteride (Proscar) showed some promise in reducing overall cancer incidence but was, unfortunately, associated with a significant increase in advanced cancers. Finasteride is therefore no longer considered suitable for prostate cancer prevention. In contrast, two natural agents, selenium and vitamin E, have been found effective in prostate cancer prevention. The Nutritional Prevention of Cancer (NPC) study concluded that supplementing with 200 micrograms/day of elemental selenium (in the form of high-selenium yeast) reduced prostate cancer risk by 63%. The large Finnish ATBC study concluded that supplementing with 50 mg/day (50 IU/day) of synthetic alpha-tocopheryl-acetate reduced prostate cancer risk and mortality by 32% and 41% respectively.

Based on these and other findings, the National Cancer Institute has embarked upon a major trial, the Selenium and Vitamin E Cancer Prevention Trial (SELECT). The trial, opened for recruitment in July 2001, now has a total enrollment of 35,534 men with a median age of 62 years (range of 50-93 years) who were free of prostate cancer. The expected follow-up time is 7-12 years. After much deliberation and a thorough review of the literature, the SELECT Steering Committee decided that the supplements to be evaluated would be 200 micrograms/day of elemental selenium in the form of L-selenomethionine and 400 IU/day of synthetic alpha-tocopheryl acetate. The trial design will involve 5 pair-wise comparisons of prostate cancer incidence, in association with – vitamin E vs placebo, selenium vs placebo, vitamin E plus selenium (combination) vs placebo, combination vs vitamin E, and combination vs selenium. The Steering Committee points out that there is strong evidence that 200 micrograms/day of elemental selenium is entirely safe, as is up to 1000 mg/day of vitamin E. They acknowledge that natural alpha-tocopherol is significantly more effective than synthetic alpha-tocopheryl acetate and that gamma-tocopherol may be even more effective than either as far as prostate cancer prevention is concerned. However, due to the fact that more clinical trial data is available on synthetic alpha-tocopheryl acetate they decided to go ahead with this form. All study participants will also receive a daily multivitamin devoid of selenium and vitamin E, but including 400 IU of vitamin D3.
Lippman, SM, et al. Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Journal of the National Cancer Institute, Vol. 97, January 19, 2005, pp. 94-102

Editor’s comment: It is indeed gratifying to see such a massive undertaking by the National Cancer Institute aimed at evaluating natural supplements in the prevention of prostate cancer. Personally, I would have liked to see the vitamin E component consist of a 50:50 mixture of natural alpha- and gamma-tocopherols, but the Steering Committee obviously decided that there was not enough evidence to support this. In any case, involving over 35,000 men in a 7- to 12-year trial of selenium and vitamin E clearly shows that hopes are high that these two natural compounds will prove effective in prostate cancer prevention and that they are entirely safe. In view of this, I see no reason to wait 10 or more years for the results to be published. All men should supplement with selenomethionine and natural vitamin E (preferably a 50:50 mixture of alpha- and gamma-tocopherols).

Diabetes protects against prostate cancer

ATLANTA, GEORGIA. The possible protective effect of diabetes against prostate cancer has been investigated once more, this time in a prospective study. Earlier studies have shown a reduction in risk of 10 to 40 per cent, and some suggest that diabetes is protective only several years after diagnosis. Researchers from the American Cancer Society used data on a group of 72,670 men from the Cancer Prevention Study II Nutrition Cohort. Information on diabetes and prostate cancer was gathered in 1982, 1992, 1997, 1999 and 2001. Prostate cancer was diagnosed in 5,318 men (7.3 per cent), who tended to be older and with a higher BMI.

The researchers found that overall; diabetes reduced the risk of prostate cancer by 33 per cent once age, race, education and prostate-specific antigen testing were taken into account. However, risk was significantly increased (by 23 per cent) in the first three years after diabetes diagnosis, compared with non- diabetic men, and only began to be protective after four years. The protective effect remained consistent when stage or grade of prostate cancer at diagnosis was examined. These results are consistent with the hypothesis that diabetes is associated with reduced risk of prostate cancer but only several years after diagnosis of diabetes, say the authors. The protective effect may be due to the reduced insulin levels found in men who have been diabetic for some time, as prostate cancer has been linked to high circulating levels of insulin.

The findings in the present study are consistent with results from a Health Professionals Follow-up Study, which also found an increased risk following diagnosis of diabetes and a protective effect after several years. In this study, prostate cancer risk was lowest 10 years after diabetes diagnosis, a reduction of 46 per cent. On the other hand, a recent case-control study within the US Physicians’ Health Study found a reduction in risk of 36 per cent, but with no link to the time since diabetes diagnosis.
Rodriguez, C et al. Diabetes and Risk of Prostate Cancer in a Prospective Cohort of US Men. American Journal of Epidemiology, Vol. 161, January 2005, pp. 147-152

Fish oils help prevent prostate cancer

BETHESDA, MARYLAND. Alpha-linolenic acid (ALA) is a major component of flax seed oil and has been associated with significant cardiovascular benefits. Some studies, however, have shown that a high intake of ALA is associated with an increased risk of prostate cancer. A prestigious team of researchers from the National Cancer Institute, the Harvard Medical School, the Harvard School of Public Health, and the Karolinska Institutet in Stockholm has just released the results of a study aimed at settling the controversy as to whether or not ALA is detrimental when it comes to prostate cancer. The researchers also determined the effect of other fatty acids, including fish oils, on prostate cancer risk.

The study involved 47,866 male American health professionals who were followed over a 14-year period beginning in 1986. The participants completed detailed food frequency questionnaires in 1986, 1990 and 1994. By the year 2000, 2965 new cases of prostate cancer had been reported with 448 of these being advanced (metastasized) or fatal. The overall incidence of new prostate cancer detected over the 14- year period was 0.5% per year.

The researchers found no correlation between ALA intake and overall prostate cancer risk, but did observe a strong association between a high ALA intake and the risk of advanced prostate cancer. Men with a high ALA intake (greater than 0.58% of energy or about 1.3 grams/day) were twice as likely to develop advanced prostate cancer as were men with a lower intake (less than 0.37% of energy or about 0.8 grams/day) even after adjusting for all other known variables that could affect the risk. The risk was slightly higher for ALA from non-animal sources than for ALA from meat and dairy sources. There was a trend for red meat, mayonnaise and salad dressings to be associated with a higher risk. The intake of two other abundant fatty acids, linoleic acid and arachidonic acid, was not related to prostate cancer risk.

The team of researchers found a protective effect associated with a high intake of fish oils - eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Men with a daily intake of more than 0.214% of daily energy (about 470 mg/day) were 11% less likely to develop prostate cancer than were men with an intake less than 0.057% of energy (about 125 mg/day). The beneficial effect of EPA plus DHA was particularly pronounced in regard to the incidence of advanced prostate cancer. Fish oil supplements were slightly less effective than fish oils from fatty fish perhaps indicating that vitamin D and vitamin A are necessary to obtain the maximum benefit.
Leitzmann, MF, et al. Dietary intake of n-3 and n-6 fatty acids and the risk of prostate cancer. American Journal of Clinical Nutrition, Vol. 80, July 2004, pp. 204-16

Selenium and prostate cancer risk

BOSTON, MASSACHUSETTS. At least five major clinical trials have concluded that higher levels of selenium (in blood or toenail clippings) are associated with a sharply reduced risk of prostate cancer. The Nutritional Prevention of Cancer (NPC) trial found that supplementing with 200 micrograms/day of selenium cuts prostate cancer risk in half. Researchers at the Harvard Medical School now weigh in with another study confirming the beneficial effects of selenium. Their study involved 22,000 healthy, male physicians who were enrolled in the study in 1982 and had blood samples taken at that time. Sufficient samples to analyze for selenium content and PSA level were available for 586 men diagnosed with prostate cancer as well as for 577 controls matched for age and smoking status.

After 13 years of follow-up the researchers concluded that study participants with a plasma selenium level of 0.12-0.19 ppm had a 50% lower incidence of advanced prostate cancer than did men with a level of 0.06-0.09 ppm. The correlation was only apparent in men with a PSA level of more than 4 ng/mL and was particularly strong for those with a baseline (1982) PSA level greater than 10 ng/mL. For these men a high selenium level corresponded to a 70% decrease in the risk of advanced prostate cancer. The researchers also observed a trend for a lower incidence of localized prostate cancer with high selenium levels, but this trend was not statistically significant. They conclude that selenium is perhaps not too effective in preventing the initiation of prostate cancer, but that it is highly effective in slowing down tumor progression. They believe that selenium acts by selectively killing off cells whose DNA has been extensively damaged, by inhibiting cellular proliferation, and by its role as a key component of glutathione peroxidase, which protects cells from peroxide damage.
Li, H, et al. A prospective study of plasma selenium levels and prostate cancer risk. Journal of the National Cancer Institute, Vol. 96, May 5, 2004, pp. 696-703
Taylor, PR, et al. Science peels the onion of selenium effects on prostate carcinogenesis. Journal of the National Cancer Institute, Vol. 96, May 5, 2004, pp. 645-47 (editorial)

Editor’s comment: The evidence is now indeed overwhelming that selenium helps protect against prostate cancer. While this study concluded that the protection mainly involves slowing down tumor progression, other studies have shown that selenium also helps prevent initiation of the cancer. Thus daily supplementation with 200 micrograms of selenium should be an integral part of all supplementation programs for men.

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