prostate cancer

Prostate Cancer What every man should know to protect his health.

More about Prostate Cancer: Causes and symptoms Diagnosis Treatment Alternative treatment Prevention Resources

Definition

Prostate cancer is a disease in which cells of the prostate become abnormal and start to grow uncontrollably, forming tumors.

Description

Prostate cancer is a malignancy of one of the major male sex glands. Along with the testicles and the seminal vesicles, the prostate secretes the fluid that makes up semen. The prostate is about the size of a walnut and lies just behind the urinary bladder. A tumor in the prostate interferes with proper control of the bladder and normal sexual functioning. Often the first symptom of prostate cancer is difficulty in urinating. However, because a very common, non-cancerous condition of the prostate, benign prostatic hyperplasia (BPH), also causes the same problem, difficulty in urination is not necessarily due to cancer.

Cancerous cells within the prostate itself are generally not deadly on their own. However, as the tumor grows, some of the cells break off and spread to other parts of the body through the lymph or the blood, a process known as metastasis. The most common sites for prostate cancer to metastasize are the seminal vesicles, the lymph nodes, the lungs, and various bones around the hips and the pelvic region. The effects of these new tumors are what can cause death.

Second only to skin cancer, the American Cancer Society estimates that in 2000 at least 180,400 new cases of prostate cancer were diagnosed. Of this number, the disease will cause at least 31,900 deaths. Although prostate cancer is often very slow growing, it can be aggressive, especially in younger men. Given its slow growing nature, many men with the disease die of other causes rather than from the cancer itself.

Prostate cancer affects African-American men twice as often as white men and the mortality rate among African-Americans is also two times higher. African-Americans have the highest rate of prostate cancer of any world population group.

— Lata Cherath; Michelle Johnson, MS, JD

For more information on prostate cancer, visit Britannica.com.

Key Terms: Antiandrogen, Benign Prostate Hyperplasia, Brachytherapy, Gleason Grading System, Granulocyte/macrophage colony stimulating factor, Histopathology, Luteinizing hormone releasing hormone (LHRH) agonist, Orchiectomy, Prostate-Specific Antigen, Radical Prostatectomy.

Definition

Prostate cancer is a disease in which cells in the prostate gland become abnormal and start to grow uncontrollably, forming tumors.

Description

Prostate cancer is a malignancy of one of the major male sex glands. Along with the testicles and the seminal vesicles, the prostate secretes the fluid that makes up semen. The prostate is about the size of a walnut and lies just behind the urinary bladder. A tumor in the prostate interferes with proper control of the bladder and normal sexual functioning. Often the first symptom of prostate cancer is difficulty in urinating. However, because a very common, non-cancerous condition of the prostate, benign prostatic hyperplasia (BPH), also causes the same problem, difficulty in urination is not necessarily due to cancer.

Cancerous cells within the prostate itself are generally not deadly on their own. However, as the tumor grows, some of the cells break off and spread to other parts of the body through the lymph or the blood, a process known as metastasis. The most common sites for prostate cancer to metastasize are the seminal vesicles, the lymph nodes, the lungs, and various bones around the hips and the pelvic region. The effects of these new tumors are what can cause death.

Demographics

Prostate cancer is the most commonly diagnosed malignancy among adult males in Western countries. Although prostate cancer is often very slow growing, it can be aggressive, especially in younger men. Given its slow growing nature, many men with the disease die of other causes rather than from the cancer itself.

Prostate cancer affects African-American men twice as often as white men; the mortality rate among African-Americans is also two times higher. African-Americans have the highest rate of prostate cancer of any world population group.

Causes and Symptoms

The precise cause of prostate cancer is not known. However, there are several known risk factors for disease including age over 55, African-American heritage, a family history of the disease, occupational exposure to cadmium or rubber, and a high-fat diet. Men with high plasma testosterone levels may also have an increased risk for developing prostate cancer.

Frequently, prostate cancer has no symptoms and the disease is diagnosed when the patient goes for a routine screening examination. However, when the tumor is big or the cancer has spread to the nearby tissues, the following symptoms may be seen:

• weak or interrupted flow of the urine
• frequent urination (especially at night)
• difficulty starting urination
• inability to urinate
• pain or burning sensation when urinating
• blood in the urine
• persistent pain in lower back, hips, or thighs (bone pain)
• painful ejaculation

Diagnosis

Prostate cancer is curable when detected early. Yet the early stages of prostate cancer are often asymptomatic, so the disease often goes undetected until the patient has a routine physical examination. Diagnosis of prostate cancer can be made using some or all of the following tests.

Digital Rectal Examination (DRE)

In order to perform this test, the doctor puts a gloved and lubricated finger (digit) into the rectum to feel for any lumps in the prostate. The rectum lies just behind the prostate gland, and a majority of prostate tumors begin in the posterior region of the prostate. If the doctor does detect an abnormality, he or she may order more tests in order to confirm these findings.

Blood Tests

Blood tests are used to measure the amounts of certain protein markers, such as prostate-specific antigen (PSA), found circulating in the blood. The cells lining the prostate generally make this protein and a small amount can be detected normally in the bloodstream. In contrast, prostate cancers produce a lot of this protein, significantly raising the circulating levels. A finding of a PSA level higher than normal for the patient's age group therefore suggests that cancer is present.

Transrectal Ultrasound

A small probe is placed in the rectum and sound waves are released from the probe. These sound waves bounce off the prostate tissue and an image is created. Since normal prostate tissue and prostate tumors reflect the sound waves differently, the test is an efficient and accurate way to detect tumors. Though the insertion of the probe into the rectum may be slightly uncomfortable, the procedure is generally painless and only takes 20 minutes.

Prostate Biopsy

If cancer is suspected from the results of any of the above tests, the doctor will remove a small piece of prostate tissue with a hollow needle. This sample is then checked under the microscope for the presence of cancerous cells. Prostate biopsy is the most definitive diagnostic tool for prostate cancer, and this procedure is done quickly and with little pain or discomfort.

Prostate cancer can also be diagnosed based on the examination of the tissue removed during a transurethral resection of the prostate (TURP). This procedure is performed to help alleviate the symptoms of BPH, a benign enlargement of the prostate. Like a biopsy, this is a definitive diagnostic method for prostate cancer.

X Rays and Imaging Techniques

A chest x ray may be ordered to determine whether the cancer has spread to the lungs. Imaging techniques (such as computed tomography (CT) scans and magnetic resonance imaging (MRI)), where a computer is used to generate a detailed picture of the prostate and areas nearby, may be done to get a clearer view of the internal organs. A bone scan may be used to check whether the cancer has spread to the bone.

Treatment Team

Prostate cancer is often treated by a team of specialists including a urologist (who may or may not perform surgery), a surgeon (if surgical treatment is used and it is not performed by the urologist), a medical oncologist, and, if radiation therapy is used, a radiation oncologist.

Clinical Staging, Treatments, and Prognosis

Once cancer is detected during the microscopic examination of the prostate tissue during a biopsy or TURP, doctors will determine two different numerical scores that will help define the patient's treatment and prognosis.

Tumor Grading

Initially, the pathologist will grade the tumor based on his or her examination of the biopsy tissue. The pathologist scores the appearance of the biopsy sample using the Gleason system. This system uses a scale of one to five based on the sample's similarity or dissimilarity to normal prostate tissue. If the tissue is very similar to normal tissue, it is still well differentiated and given a low grading number, such as one or two. As the tissue becomes more and more abnormal (less and less differentiated), the grading number increases, up to five. Less differentiated tissue is considered more aggressive and more likely to be the source of metastases.

The Gleason grading system is best predictive of the prognosis of a patient if the pathologist gives two scores to a particular sample—a primary and a secondary pattern. The two numbers are then added together and that is the Gleason score reported to the patient. Thus, the lowest Gleason score available is two (a primary and secondary pattern score of one each). A typical Gleason score is five (which can be a primary score of two and a secondary score of three or visa-versa). The highest score available is 10, with a pure pattern of very undifferentiated tissue, that is, of grade five. The higher the score, the more abnormal behavior of the tissue, the greater the chance for metastases, and the more serious the prognosis after surgical treatment. A study found that the ten-year cancer survival rate without evidence of disease for grade two, three, and four cancers is 94% of patients. The rate is 91% for grade five cancers, 78% for grade six, 46% for grade seven, and 23% for grade eight, nine, and ten cancers.

Cancer Staging

The second numeric score determined by the doctor will be the stage of the cancer, which takes into account the grade of the tumor determined by the pathologist. Based on the recommendations of the American Joint Committee on Cancer (AJCC), two kinds of data are used for staging prostate cancer. Clinical data is based on the external symptoms of the cancer, while histopathological data is based on surgical removal of the prostate and examination of its tissues. Clinical data is most useful to make treatment decisions, while pathological data is the best predictor of prognosis. For this reason, the staging of prostate cancer takes into account both clinical and histopathologic information. Specifically, doctors look at tumor size (T), lymph node involvement (N), the presence of visceral (internal organ) involvement (metastasis = M), and the grade of the tumor (G).

The classification of tumor as T1 means the cancer that is confined to the prostate gland and the tumor that is too small to be felt during a DRE. T1 tumors are often found after examination of tissue removed during a TURP. The T1 definition is subdivided into those cancers that show less than 5% cancerous cells in the tissue sample (T1a) or more than 5% cancerous cells in the tissue sample (T1b). T1c means that the biopsy was performed based on an elevated PSA result. The second tumor classification is T2, where the tumor is large enough to be felt during the DRE. T2a indicates that only the left or the right side of the gland is involved, while T2b means both sides of the prostate gland has tumor.

With a T3 tumor, the cancer has spread to the connective tissue near the prostate (T3a) or to the seminal vesicles as well (T3b). T4 indicates that cancer has spread within the pelvis to tissue next to the prostate such as the bladder's sphincter, the rectum, or the wall of the pelvis. Prostate cancer tends to spread next into the regional lymph nodes of the pelvis, indicated as N1. Prostate cancer is said to be at the M1 stage when it has metastasized outside the pelvis in distant lymph nodes (M1a), bone (M1b) or organs such as the liver or the brain (M1c). Pain, weight loss, and fatigue often accompany the M1 stage.

The grade of the tumor (G) can be assessed during a biopsy, TURP surgery, or after removal of the prostate. There are three grades recognized: G1, G2, and G3, indicating the tumor is well, moderately, or poorly differentiated, respectively. The G, LN, M descriptions are combined with the T definition to determine the stage of the prostate cancer.

• Stage I prostate cancer comprises patients who are T1a, N0, M0, G1.
• Stage II includes a variety of condition combinations including T1a, N0, M0, G2, 3 or 4; T1b, N0, M0, Any G; T1c, N0, M0, Any G; T1, N0, M0, Any G or T2, N0, M0, Any G.
• Stage III prostate cancer occurs when conditions are T3, N0, M0, any G.
• Stage IV is T4, N0, M0, any G; any T, N1, M0, any G; or any T, any N, M1, Any G.

Prognosis

The prognosis for cancers at Stages I and II is very good. For men treated with stage I or stage II disease, over 95% are alive after five years. Although the cancers of Stage III are more advanced, the five-year prognosis is still good, with 70% of men diagnosed at this stage still living. The spread of the cancer into the pelvis (T4), lymph (N1), or distant locations (M1) are very significant events, as the five-year survival rate drops to 30% for Stage IV.

Treatment Options

The doctor and the patient will decide on the treatment mode after considering many factors. For example, the patient's age, the stage of the disease, his general health, and the presence of any co-existing illnesses have to be considered. In addition, the patient's personal preferences and the risks and benefits of each treatment protocol are also taken into account before any decision is made.

Surgery

For stage I and stage II prostate cancer, surgery is the most common method of treatment because it theoretically offers the chance of completely removing the cancer from the body. Radical prostatectomy involves complete removal of the prostate. The surgery can be done using a perineal approach, where the incision is made between the scrotum and the anus, or using a retropubic approach, where the incision is made in the lower abdomen. Perineal approach is also known as nerve-sparing prostatectomy, as it is thought to reduce the effect on the nerves and thus reduce the side effects of impotence and incontinence. However, the retropubic approach allows for the simultaneous removal of the pelvic lymph nodes, which can give important pathological information about the tumor spread.

The drawback to surgical treatment for early prostate cancer is the significant risk of side effects that impact the quality of life of the patient. Even using nerve-sparing techniques, studies by the National Cancer Institute (NCI) found that 60% to 80% of men treated with radical prostatectomy reported themselves as impotent (unable to achieve an erection sufficient for sexual intercourse) two years after surgery. This side effect can be sometimes countered by prescribing sildenafil citrate (Viagra). Furthermore, 8% to 10% of patients were incontinent in that time span. Despite the side effects, the majority of men were reported as satisfied with their treatment choice. Additionally, there is some evidence that the skill and the experience of the surgeon are central factors in the ultimate side effects seen.

A second method of surgical treatment of prostate cancer is cryosurgery, or cryotherapy. Guided by ultrasound, surgeons insert up to eight cryoprobes through the skin and into close proximity with the tumor. Liquid nitrogen (temperature of -320.8 degrees F, or -196 C) is circulated through the probe, freezing the tumor tissue. In prostate surgery, a warming tube is also used to keep the urethra from freezing. Patients currently spend a day or two in the hospital following the surgery, but it could be an outpatient procedure in the near future. Recovery time is about one week. Side effects have been reduced in recent years, although impotence still affects almost all who have had cryosurgery for prostate cancer. Cryo-surgery is considered a good alternative for those too old or sick to have traditional surgery or radiation treatments or when these more traditional treatments are unsuccessful. There is limited amount of information about the long-term efficacy of this treatment for prostate cancer.

RADIATION THERAPY Radiation therapy involves the use of high-energy x rays to kill cancer cells or to shrink tumors. It can be used instead of surgery for stage I and II cancer. The radiation can either be administered from a machine outside the body (external beam radiation), or small radioactive pellets can be implanted in the prostate gland in the area surrounding the tumor, called brachytherapy or interstitial implantation. Pellets containing radioactive iodine (I-125), palladium (Pd 103), or iridium (Ir 192) can be implanted on an outpatient basis, where they remain permanently. The radioactive effect of the seeds last only about a year.

The side effects of radiation can include inflammation of the bladder, rectum, and small intestine as well as disorders of blood clotting (coagulopathies). Impotence and incontinence are often delayed side effects of the treatment. A study indicated that bowel control problems were more likely after radiation therapy when compared to surgery, but impotence and incontinence were more likely after surgical treatment. Long-term results with radiation therapy are dependent on stage. A review of almost 1,000 patients treated with megavoltage irradiation showed 10-year survival rates to be significantly different by T-stage: T1 (79%), T2 (66%), T3 (55%), and T4 (22%). There does not appear to be a large difference in survival between external beam or interstitial treatments.

Hormone Therapy

Hormone therapy is commonly used when the cancer is in an advanced stage and has spread to other parts of the body, such as stage III or stage IV. Prostate cells need the male hormone testosterone to grow. Decreasing the levels of this hormone or inhibiting its activity will cause the cancer to shrink. Hormone levels can be decreased in several ways. Orchiectomy is a surgical procedure that involves complete removal of the testicles, leading to a decrease in the levels of testosterone. Another method tricks the body by administering the female hormone estrogen. When estrogen is given, the body senses the presence of a sex hormone and stops making the male hormone testosterone. However, there are some unpleasant side effects to hormone therapy. Men may have "hot flashes," enlargement and tenderness of the breasts, or impotence and loss of sexual desire, as well as blood clots, heart attacks, and strokes, depending on the dose of estrogen. Another side effect is osteoporosis, or loss of bone mass leading to brittle and easily fractured bones.

Watchful Waiting

Watchful waiting means no immediate treatment is recommended, but doctors keep the patient under careful observation. This is often done using periodic PSA tests. This option is generally used in older patients when the tumor is not very aggressive and the patients have other, more life-threatening, illnesses. Prostate cancer in older men tends to be slow-growing. Therefore, the risk of the patient dying from prostate cancer, rather than from other causes, is relatively small.

Alternative and Complementary Therapies

Alternative treatments that have been found helpful in coping with the emotional stress associated with prostate cancer include meditation, guided imagery, and relaxation techniques. Acupuncture is effective in relieving pain in some patients.

A variety of herbal products have been used to treat prostate cancer, including various compounds used in traditional Chinese medicine as well as single agents like Reishi mushrooms (Ganoderma lucidum). One herbal compound that was under investigation by the National Center for Complementary and Alternative Medicine (NCCAM) as a possible treatment for prostate cancer was PC-SPES, a mixture of eight herbs adapted from traditional Chinese medicine. In the summer of 2002, however, NCCAM put its studies of PC-SPES on hold when the Food and Drug Administration (FDA) determined that samples of the product were contaminated with undeclared prescription drug ingredients. PC-SPES was withdrawn from the American market in late 2002.

Coping With Cancer Treatment

The treatment process for prostate cancer can be a physically and emotionally exhausting time. Here are six general suggestions that can help make the process easier. Patients should:

• put their faith and trust in their doctors once a treatment course has been chosen
• remember that a patient is never without power and rights during the course of treatment
• put practical affairs in order
• closely monitor each step of the treatment
• keep close family and friends informed and delegate responsibilities as necessary
• work to make visits pleasant and comfortable

• be careful to eat, sleep, exercise, and conduct daily activities in a healthy manner

Clinical Trials

Patients with extraprostatic disease are suitable candidates for clinical trials. One trial is the testing of a vaccine (GVAX) that causes the body to mount an immune response against all prostate cells. As the prostate is a nonessential organ, the destruction of the normal cells with the tumor cells is not a problem. The vaccine was made using cancer cells from a tumor that had been genetically engineered to express granulocyte/macro-phage colony-stimulating factor (GM-CSF), a potent activator of the entire immune system. The additional protein jumpstarted the immune response against the prostate cells upon vaccination and resulted in anti-tumor immune response.

Other trials for prostate cancer include evaluation of combination therapies, such as postoperative radiation delivery, use of cytotoxic agents, and hormonal treatment using luteinizing hormone-releasing hormone (LHRH) agonists and/or antiandrogens to shut down the growth of the hormone-dependent tumors. Other drugs that are being tested as of 2003 are chemoprotective agents like amifostine (Ethyol), which are given to prostate cancer patients to counteract the harmful side effects of radiation treatment.

Prevention

Because the cause of the cancer is not known, there is no definite way to prevent prostate cancer. Given its common occurrence and the low cost of screening, the American Cancer Society (ACS) and the National Comprehensive Cancer Network (NCCN) recommends that all men over age 40 have an annual rectal exam and that men have an annual PSA test beginning at age 50. African-American men and men with a family history of prostate cancer, who have a higher than average risk, should begin annual PSA testing even earlier, starting at age 45.

However, mandatory screening for prostate cancer is controversial. Because the cancer is so slow growing, and the side effects of the treatment can have significant impact on patient quality of life, some medical organizations question the wisdom of yearly exams. Some organizations have even noted that the effect of screening is discovering the cancer at an early stage when it may never grow to have any outward effect on the patient during this lifetime. Nevertheless, the NCI reports that the current aggressive screening methods have achieved a reduction in the death rate of prostate cancer of about 2.3% for African-Americans and about 4.6% for Caucasians since the mid-1990s, with a 20% increase in overall survival rate during that period.

A low-fat diet may slow the progression of prostate cancer. To reduce the risk or progression of prostate cancer, the American Cancer Society recommends a diet rich in fruits, vegetables and dietary fiber, and low in red meat and saturated fats.

Questions to Ask the Doctor

• How do my age, general health, and other medical conditions affect my treatment choices?
• What are the T, N, and M stages of my cancer and how do they influence my treatment options?
• How do the Gleason score of my cancer and my blood prostate-specific antigen (PSA) level predict my outlook for survival and affect treatment options?
• What are the likely side effects of each proposed therapy and how will they affect my quality of life?
• What can be done to help manage the side effects of treatment?

Special Concerns

The availability of an early detection system for prostate cancer with the development of the PSA serum test has complicated the treatment of this disease. Early detection of an often slow-growing cancer, where treatment can significantly impact the quality of life of the patient, can be complicated. Long-term studies are currently in progress that should provide the first real quantitative information about the relative efficacy of the different treatment options, the actual occurrence of side effects, and the comparative benefits of watchful waiting treatment compared with more aggressive action.

Resources

Books

Beers, Mark H., MD, and Robert Berkow, MD, editors. "Prostate Cancer." Section 17, Chapter 233 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Carroll, Peter R., et al. "Cancer of the Prostate." In Cancer Principles and Practice of Oncology, edited by Devita, Vincent T., et al. Philadelphia: Lippincott Williams & Wilkins, 2001.

Wainrib, Barbara R., and Sandra Haber. Men, Women, and Prostate Cancer. Oakland, CA: New Harbinger Productions, Inc., 2000.

Periodicals

Alimi, D., C. Rubino, E. Pichard-Leandri, et al. "Analgesic Effect of Auricular Acupuncture for Cancer Pain: A Randomized, Blinded, Controlled Trial." Journal of Clinical Oncology 21 (November 15, 2003): 4120–4126.

Chang, S. S. "Exploring the Effects of Luteinizing Hormone-Releasing Hormone Agonist Therapy on Bone Health: Implications in the Management of Prostate Cancer." Urology 62 (December 22, 2003): 29–35.

de la Fouchardiere, C., A. Flechon, and J. P. Droz. "Coagulopathy in Prostate Cancer." Netherlands Journal of Medicine 61 (November 2003): 347–354.

Dziuk, T., and N. Senzer. "Feasibility of Amifostine Administration in Conjunction with High-Dose Rate Brachytherapy." Seminars in Oncology 30 (December 2003): 49–57.

Hsieh, K., and P. C. Albertsen. "Populations at High Risk for Prostate Cancer." Urological Clinics of North America 30 (November 2003): 669–676.

Linares, L. A., and D. Echols. "Amifostine and External Beam Radiation Therapy and/or High-Dose Rate Brachytherapy in the Treatment of Localized Prostate Carcinoma: Preliminary Results of a Phase II Trial." Seminars in Oncology 30 (December 2003): 58–62.

Sliva, D. "Ganoderma lucidum (Reishi) in Cancer Treatment." Integrative Cancer Therapies 2 (December 2003): 358–364.

Spetz, A. C., E. L. Zetterlund, E. Varenhorst, and M. Hammar. "Incidence and Management of Hot Flashes in Prostate Cancer." Journal of Supportive Oncology 1 (November-December 2003): 263–273.

Wilson, S. S., and E. D. Crawford. "Prostate Cancer Update." Minerva Urologica e Nefrologica 55 (December 2003): 199–204.

Organizations

The Association for the Cure of Cancer of the Prostate (CaPCure). 1250 Fourth St., Suite 360, Santa Monica, CA 90401. (800) 757-CURE. .

National Cancer Institute. Building 31, Room 10A31 31 Center Drive, MSC 2580, Bethesda, MD 20892-2580. (800) 4-CANCER. .

National Center for Complementary and Alternative Medicine (NCCAM) Clearinghouse. P. O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226. .

Other

FDA MedWatch Safety Alert for PC-SPES, SPES, updated September 20, 2002. .

National Center for Complementary and Alternative Medicine (NCCAM). Recall of PC-SPES and SPES Dietary Supplements. NCCAM Publication No. D149, September 2002. .

—Lata Cherath, Ph.D.; Michelle Johnson, M.S., J.D.; Rebecca J. Frey, PhD

A slowly progressive adenocarcinoma of the prostate gland that affects an increasing proportion of American males after the age of 50. It is the third leading cause of cancer deaths with more than 120,000 new cases reported in the United States each year.

Definition

Prostate cancer is a disease in which the cells of the prostate become abnormal and start to grow uncontrollably, forming tumors. Tumors that can spread to other parts of the body are called malignant tumors or cancers. Tumors incapable of spreading are said to be benign.

Description

Prostate cancer is the most common cancer among men in the United States, and is the second leading cause of cancer deaths. The American Cancer Society (ACS) estimates that in 1998, at least 185,000 new cases of prostate cancer will be diagnosed, and it will be the cause of at least 40,000 deaths. Although prostate cancer may be very slow-growing, it is a heterogeneous disease and can be quite aggressive, especially in younger men. When the disease is slow-growing, it may often go undetected. Because it may take many years for the cancer to develop, many men with the disease will probably die of other causes, rather than from the cancer itself.

Prostate cancer affects African American men twice as often as it does Caucasian men, and the mortality rate among African Americans is also two times higher. African Americans have the highest rate of prostate cancer in the world.

The prostate, testicles, and seminal vesicles are the major male sex glands. These three glands together secrete the fluid that makes up semen. The prostate is about the size of a walnut and lies just behind the urinary bladder. A tumor in the prostate interferes with proper control of the bladder and normal sexual functions. Often, the first symptom of prostate cancer to develop is difficulty in urinating. However, because the same symptom can be caused by a very common, noncancerous condition of the prostate (benign prostatic hyperplasia), it does not always mean that prostate cancer is present.

As the prostate cancer grows, some of the cells break off and spread to other parts of the body through the lymph or the blood. The most common sites to which it spreads are the lymph nodes, the lungs, and various bones around the hips and the pelvic region.

Causes & Symptoms

The cause of prostate cancer is not known, however, it is found mainly in men over the age of 55. The average age at diagnosis is 72. In fact, 80% of the prostate cancer cases occur in men over the age of 65. While only 1 in 100,000 men will get prostate cancer under the age of 40, the frequency rises to 1,326 cases in 100,000 for men between the ages of 70 and 74. Hence, age appears to be a risk factor for prostate cancer. Race may be another contributing factor, because African-Americans have the highest rate of prostate cancer in the world.

Some studies have shown that a family history of prostate cancer puts a man at a higher risk for developing this disease. In addition, there is some evidence to suggest that a diet high in fat increases the risk of prostate cancer. Workers in the electroplating and welding industries who are exposed to the metal cadmium and rubber industry workers appear to have a higher than average risk of getting this disease. Research has indicated that men with high plasma testosterone levels also may be at an increased risk.

Frequently, prostate cancer has no symptoms, and the disease is diagnosed when the patient goes for a routine screening examination. However, occasionally, when the tumor becomes large or the cancer has spread to the nearby tissues, the following symptoms may be seen:

• weak or interrupted flow of the urine
• frequent urination (especially at night)
• difficulty starting urination
• inability to urinate
• pain or burning sensation when urinating
• blood in the urine
• persistent pain in lower back, hips, or thighs (bone pain)
• painful ejaculation

Diagnosis

Prostate cancer is curable when detected early. However, because the early stages of prostate cancer may not have any visible symptoms, it often goes undetected until the patient goes for a routine physical examination. Diagnosis of the disease is made using some or all of the following tests.

Digital Rectal Examination (DRE)

In order to perform this test, the doctor puts a gloved, lubricated finger (digit) into the rectum to feel for any lumps in the prostate. The rectum lies just behind the prostate gland, and a majority of prostate tumors begin in the posterior region of the prostate. If the doctor does detect an abnormality, he or she may order more tests in order to confirm these findings.

BLOOD TESTS. Blood tests are used to measure the amounts of certain protein markers, such as prostate-specific antigen (PSA), found circulating in the blood. The cells lining the prostate generally make this protein and a small amount can be detected in the bloodstream. However, prostate cancers produce a lot of this protein, and it can be easily detected in the blood. Hence, when PSA is found in the blood in higher than normal amounts for the patient's particular age group, cancer may be present.

TRANSRECTAL ULTRASOUND. A small probe is placed in the rectum, and sound waves are released from the probe. These sound waves bounce off the prostate tissue and an image is created. Since normal prostate tissue and prostate tumors reflect the sound waves differently, the test can be used to detect tumors quite efficiently. Though the insertion of the probe into the rectum may be slightly uncomfortable, the procedure is generally painless and takes only 20 minutes.

PROSTATE BIOPSY. If cancer is suspected from the results of any of the above tests, the doctor will remove a small piece of prostate tissue with a hollow needle. This sample is then checked under the microscope for the presence of cancerous cells. Prostate biopsy is the most definitive diagnostic tool for prostate cancer.

If cancer is detected during the microscopic examination of the prostate tissue, the pathologist will "grade" the tumor using a method called the Gleason system. This means that he or she will score the tumor on a scale of 1–10 to indicate how aggressive the tumor is. Tumors with a lower score are less likely to grow and spread than are tumors with higher scores. The Gleason system is different from "staging" of the cancer. When a doctor stages a cancer, he or she gives it a number that indicates whether it has spread, as well as the extent of its spread. In Stage I, the cancer is localized in the prostate in one area, while in the last stage, Stage IV, the cancer cells have spread to other parts of the body.

X RAYS AND IMAGING TECHNIQUES. A chest x ray may be ordered to determine whether the cancer has spread to the lungs. Imaging techniques (such as computed tomography scans and magnetic resonance imaging), where a computer is used to generate a detailed picture of the prostate and areas nearby, may be done to get a clearer view of the internal organs. A bone scan also may be used to check whether the cancer has spread to the bone.

Treatment

The doctor and the patient will decide on the treatment mode after considering many factors. Such factors include the patient's age, the stage of the tumor, his general health, and the presence of any co-existing illnesses. In addition, the patient's personal preferences and the risks and benefits of each treatment protocol are also taken into account before any decision is made.

Various natural remedies used to treat noncancerous prostate problems can be implemented with the approval of a medical doctor along with the recommended medical care. Prostate enlargement is a precursor to prostate cancer, and many alternative treatments are available to alleviate benign prostate enlargement. Among those is the herb saw palmetto, which has shown to be highly effective in the treatment of prostate enlargement. In addition, treatments that focus on strengthening the immune system of the cancer patient can be helpful, using physiologic and psychologic therapies.

Lycopene, the antioxidant found in tomatoes and tomato products, has long been thought to help prevent prostate cancer. In the first clinical intervention trial of prostate cancer patients in 2001, lycopene supplementation slowed the progression of prostate camcer.

Visualization of a healthy, cancer-free body, and of cancer cells as weak and confused is believed to be healing imagery. Numerous studies affirm the power of a positive mental attitude in assisting conventional medical treatment to be more effective, while at the same time, minimizing undesirable side effects of chemotherapy or radiation.

Compounds contained in maitake mushrooms are believed to enhance the immune response and slow the growth of tumors. One study by a homeopathic physician, Dr. Abram Ber of Phoenix, Arizona, found that patients with prostate cancer treated with maitake mushroom tablets reported a decrease in the urge to urinate, along with improvement in the flow of urine.

Watchful Waiting

Watchful waiting means no immediate treatment is recommended, but doctors keep the patient under careful observation. This option is generally used in older patients when the tumor is not very aggressive and the patients have other, more life-threatening illnesses. Prostate cancer in older men tends to be slow-growing. Therefore, the risk of the patient dying from prostate cancer, rather than from other causes, is relatively small.

Allopathic Treatment

Surgery

For early stage prostate cancer, surgery is the best option and the most common one. Radical prostatectomy involves complete removal of the prostate. During the surgery, a sample of the lymph nodes near the prostate is removed to determine whether the cancer has spread beyond the prostate gland. Because the seminal vesicles (the glands where sperm is made) are removed along with the prostate, infertility is a side effect of this type of surgery. In order to minimize the risk of impotence (inability to have an erection) and incontinence (inability to control urine flow), a procedure known as "nervesparing" prostatectomy is used.

In a different surgical method, known as the transurethral resection procedure or TURP, only the cancerous portion of the prostate is removed, by using a small wire loop that is introduced into the prostate through the urethra. This technique is most often used in men who cannot have a radical prostatectomy due to age or other illness, and it is rarely recommended.

RADIATION THERAPY. Radiation therapy involves the use of high-energy x rays to kill cancer cells or to shrink tumors. It can be used instead of surgery for early stages of cancer. The radiation can either be administered from a machine outside the body (external beam radiation), or small radioactive pellets can be implanted in the prostate gland in the area surrounding the tumor.

HORMONE THERAPY. Hormone therapy is commonly used when the cancer is in an advanced stage and has spread to other parts of the body. Prostate cells need the male hormone testosterone to grow. Decreasing the levels of this hormone, or inhibiting its activity, will cause the cancer to shrink. Hormone levels can be decreased in several ways. Orchiectomy is a surgical procedure that involves complete removal of the testicles, leading to a decrease in the levels of testosterone. Alternatively, drugs (such as LHRH agonists or anti-androgens) that bind to the male hormone testosterone and block its activity can be given. Another method "tricks" the body by administering the female hormone estrogen. When this is given, the body senses the presence of a sex hormone and stops producing testosterone. However, there are some unpleasant side effects to hormone therapy. Depending on the doses of estrogen, men may have "hot flashes," enlargement and tenderness of the breasts, impotence or loss of sexual desire, as well as the risks of blood clots, heart attacks, and strokes.

CHEMOTHERAPY. Chemotherapy is the use of drugs to kill cancer cells. The drugs can either be taken as a pill or injected into the body through a needle that is inserted into a blood vessel. This type of treatment is called systemic treatment, because the drug enters the blood stream, travels through the whole body, and kills the cancer cells that are outside the prostate. Chemotherapy is sometimes used to treat prostate cancer that has recurred after other treatment. Further research is ongoing to find more drugs that are effective for the treatment of prostate cancer.

Expected Results

According to the American Cancer Society, the survival rate for all stages of prostate cancer combined has increased from 50–87% over the last 30 years. Due to early detection and better screening methods, nearly 60% of the tumors are diagnosed while they are still confined to the prostate gland. The five-year survival rate for early stage cancers is almost 99%. Sixty three percent of the patients survive 10 years, and 51% survive 15 years after initial diagnosis.

Prevention

Because the cause of the cancer is not known, there is no definite way to prevent prostate cancer. However, the American Cancer Society recommends that all men over age 40 have an annual rectal exam and that men have an annual PSA test beginning at age 50. Those who have a higher than average risk, including African American men and men with a family history of prostate cancer, should begin annual PSA testing even earlier, starting at age 45.

A diet low in fat may slow the progression of prostate cancer. Hence, in order to reduce the risk of prostrate cancer, the American Cancer Society recommends a diet rich in fruits, vegetables, and dietary fiber, and low in red meat and saturated fats. Intake of lycopene, which is found in cooked tomatoes or tomato sauce, is also thought to help reduce the risk of prostate cancer.

Resources

Books

Dollinger, Malin. Everyone's Guide to Cancer Therapy. Somerville House Books Limited, 1994.

Morra, Marion E. Choices. New York: Avon Books, 1994.

Wallner, Kent. Prostate Cancer: A Non-Surgical Perspective. Seattle: SmartMedicine Press, 996.

Periodicals

"Clinical Intervention Trial Finds Benefit of Lycopene." Cancer Weekly (November 27, 2001) :38.

Organizations

American Cancer Society. 1599 Clifton Road NE, Atlanta, Georgia 30329. (800) 227–2345.

American Urologic Association. 1120 N. Charles Street, Baltimore, MD 21201. (410) 223–4310.

Cancer Research Institute. 681 Fifth Avenue, New York, N.Y. 10022. (800) 992–2623.

National Institutes of Health. National Cancer Institute. 9000 Rockville Pike, Bethesda, MD 20892. (800)422–6237.

National Institute on Aging Information Center. (800) 222–2225.

Zero — The Project to End Prostate Cancer. 1300 19th Street NW, Suite 400, Washington DC 20036. (202)842–3600 ext. 214.

[Article by: Kathleen Wright; Teresa G. Odle]

Prostate cancer is the most common cancer in men and the second leading cause of cancer-related death in men. An estimated 191,000 cases of prostate cancer will be diagnosed in 2001 in the United States along with 30,500 prostate cancer-related deaths. The disease is detected by a combination of abnormal serum prostate-specific antigen (PSA) and digital rectal exam (DRE), and less often as an incidental finding after prostate resection for obstructive benign disease. It is uncommon at this time to diagnose prostate cancer in association with gross urinary obstruction, bleeding, or unexplained skeletal pain.

The disease is both hereditary and sporadic with one gene (HPC2), and several gene loci recently identified. The risk for developing prostate cancer increases twofold if a first-degree relative is affected and it further increases as more family members are afflicted (first- and second-degree relatives). Although no specific cause for prostate cancer has been identified, several factors contribute to the development of the disease. This includes the level of saturated animal fat in the diet, vitamin D production, and ethnic origin. African Americans have the highest rate of prostate cancer in the world, while it is the lowest in native Asians. The disease is more commonly seen after the age of fifty.

The natural history of prostate cancer is strongly driven by the tumor grade. The risk of prostate cancer death is low (less than 10%) in patients of almost all ages with low-grade disease; however, it is substantial for patients with moderate- or high-grade disease. Metastatic disease has a very predictable natural history, with a median survival of thirty to thirty-three months after diagnosis.

Prostate cancer is generally detected by an abnormal serum PSA determination and/or an abnormal DRE. The diagnosis is generally made by an ultrasound-guided needle biopsy of the prostate. These techniques have led to a stage shift in the disease, with the majority of lesions now detected in the clinically localized state. Contemporary treatments for clinically localized disease include watchful waiting, radical prostatectomy, radiation therapy (external beam or brachytherapy), or cryosurgery. Androgen ablation (removal of testosterone-like substances from the system) can be used alone or in combination with other modalities, and is the principle form of therapy for advanced disease.

The decision whether to treat the disease or observe the patient should be based on the probability of the patient reasonably living another five to ten years, and thus takes into account the patient's age and comorbid conditions. Surgery can be very effective and is generally employed in younger men where nerve-sparing surgery can be used to preserve erectile function. The major side effect is urinary incontinence, which can be significant in a small percentage of patients. External beam radiation therapy is also a standard form of therapy which is generally performed in older patients (over age seventy). It is usually well tolerated, but a small percentage of men can develop gastrointestinal side effects related to rectal irritation.

Brachytherapy refers to the implantation of radioactive pellets in the prostate gland, usually under ultrasound guidance. This technique has been employed for approximately a decade and is an effective form of therapy in men with appropriate lesions. The major side effect from this therapy is an increase in irritative voiding symptoms. An increasing body of knowledge suggests that the addition of androgen ablation may improve the outcomes of patients receiving radiation.

Approximately 20 percent of patients treated for localized disease will experience a rise in their PSA within five years. This group of biochemical- failure patients are an enlarging cohort of patients for which exact treatment recommendations are not available. Gross loco-regional disease has become less common in the PSA era. Prostate cancer generally metastasizes to the lymph nodes and the bones, with less common involvement of the visceral organs.

Prostate tumors are classically dependent on endogenous androgens as growth factors. The removal of androgens by castration (surgical or chemical) results in a regression of symptoms and measurable disease in 80 percent of patients. Unfortunately, there are androgen-resistant clones in most tumors, which makes this form of therapy palliative. Androgen ablation can be performed by the removal of the testicles or the administration of a luteinizing hormone releasing hormone (LHRH) antagonist.

Prostate cancer relapsing after androgen ablation is designated androgen independent prostate cancer. The median survival for such patients is approximately eleven months. Although newer chemotherapy agents are displaying activity in advanced prostate cancer, treatment is generally palliative. This is an area of intense clinical investigation and protocol therapy.

(SEE ALSO: Cancer; Prostate-Specific Antigen [PSA])

Bibliography

Albertson, P. C.; Hanley, J. A.; Gleason, D. R. et al. (1998). "Competing Risk Analysis of Men Aged 55 to 74 Years at Diagnosis Managed Conservatively for Clinically Localized Prostate Cancer." Journal of the American Medical Association 280:975–980.

Catalona, W. J., and Smith, D. S. (1998). "Cancer Recurrence and Survival Rates after Anatomic Radical Retropubic Porstatectomy for Prostate Cancer: Intermediate-Term Results." Journal of Urology 160:2428–2434.

D'Amico, A. V.; Whittington, R.; Malkowicz, S. B. et al. (1998). "Biochemical Outcome after Radical Prostatectomy, External Beam Radiation Therapy or Interstitial Radiation Therapy for Clinically Localized Prostate Cancer." Journal of the American Medical Association 280:969–974.

Eisenberg, M. A.; Blumenstein, B. A.; Crawford, E. D. et al. (1998). "Bilateral Orchiectomy with or without Flutamide for Metastatic Prostate Cancer." New England Journal of Medicine 339:1036–1042.

Powel, I. J. (1998). "Prostate Cancer in the African-American: Is This a Different Disease?" Seminars in Urologic Oncology 16:221–226.

Ragde, H.; Blasko, J. C.; Grimm, P. D. et al. (1997). "Interstital Iodine-125 Radiation without Adjuvant Therapy in the Treatment of Clinically Localized Prostate Carcinoma." Cancer 80:442–453.

— S. BRUCE MALKOWICZ

Prostate cancer
Classification and external resources
Micrograph of prostate adenocarcinoma, acinar type, the most common type of prostate cancer. Needle biopsy. HPS stain.
ICD-10	C61.
ICD-9	185
OMIM	176807
DiseasesDB	10780
MedlinePlus	000380
eMedicine	radio/574
MeSH	D011471

Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. The cancer cells may metastasize (spread) from the prostate to other parts of the body, particularly the bones and lymph nodes. Prostate cancer may cause pain, difficulty in urinating, problems during sexual intercourse, or erectile dysfunction. Other symptoms can potentially develop during later stages of the disease.

Rates of detection of prostate cancers vary widely across the world, with South and East Asia detecting less frequently than in Europe, and especially the United States.^[1] Prostate cancer tends to develop in men over the age of fifty and although it is one of the most prevalent types of cancer in men, many never have symptoms, undergo no therapy, and eventually die of other causes. This is because cancer of the prostate is, in most cases, slow-growing, symptom-free, and since men with the condition are older they often die of causes unrelated to the prostate cancer, such as heart/circulatory disease, pneumonia, other unconnected cancers, or old age. Many factors, including genetics and diet, have been implicated in the development of prostate cancer. The presence of prostate cancer may be indicated by symptoms, physical examination, prostate specific antigen (PSA), or biopsy. There is controversy about the accuracy of the PSA test and the value of screening. Suspected prostate cancer is typically confirmed by taking a biopsy of the prostate and examining it under a microscope. Further tests, such as CT scans and bone scans, may be performed to determine whether prostate cancer has spread.

Treatment options for prostate cancer with intent to cure are primarily surgery, radiation therapy, and proton therapy. Other treatments, such as hormonal therapy, chemotherapy, cryosurgery, and high intensity focused ultrasound (HIFU) also exist, depending on the clinical scenario and desired outcome.

The age and underlying health of the man, the extent of metastasis, appearance under the microscope, and response of the cancer to initial treatment are important in determining the outcome of the disease. The decision whether or not to treat localized prostate cancer (a tumor that is contained within the prostate) with curative intent is a patient trade-off between the expected beneficial and harmful effects in terms of patient survival and quality of life.

Contents 1 Classification 2 Signs and symptoms 3 Causes 3.1 Genetics 3.2 Diet 3.3 Medication exposure 3.4 Potential viral cause 4 Pathophysiology 5 Diagnosis 5.1 Biopsy 5.1.1 Gleason score 5.1.2 Tumor markers 5.2 Diagnostic tools under investigation 5.2.1 PCA3 5.2.2 Early prostate cancer 5.2.3 Prostate mapping 5.3 Prostasomes 6 Prevention 6.1 Ejaculation frequency 6.2 Oils and fatty acids 6.3 Other 7 Screening 8 Management 9 Prognosis 9.1 Classification systems 10 Epidemiology 11 History 12 Research 12.1 Prostate cancer models 13 See also 14 References 15 External links

Classification

Main article: Prostate

The prostate is a part of the male reproductive organ that helps make and store seminal fluid. In adult men, a typical prostate is about three centimeters long and weighs about twenty grams.^[2] It is located in the pelvis, under the urinary bladder and in front of the rectum. The prostate surrounds part of the urethra, the tube that carries urine from the bladder during urination and semen during ejaculation.^[3] Because of its location, prostate diseases often affect urination, ejaculation, and rarely defecation. The prostate contains many small glands which make about twenty percent of the fluid constituting semen.^[4] In prostate cancer, the cells of these prostate glands mutate into cancer cells. The prostate glands require male hormones, known as androgens, to work properly. Androgens include testosterone, which is made in the testes; dehydroepiandrosterone, made in the adrenal glands; and dihydrotestosterone, which is converted from testosterone within the prostate itself. Androgens are also responsible for secondary sex characteristics such as facial hair and increased muscle mass.

Main article: Prostate cancer staging

An important part of evaluating prostate cancer is determining the stage, or how far the cancer has spread. Knowing the stage helps define prognosis and is useful when selecting therapies. The most common system is the four-stage TNM system (abbreviated from Tumor/Nodes/Metastases). Its components include the size of the tumor, the number of involved lymph nodes, and the presence of any other metastases.

The most important distinction made by any staging system is whether or not the cancer is still confined to the prostate. In the TNM system, clinical T1 and T2 cancers are found only in the prostate, while T3 and T4 cancers have spread elsewhere. Several tests can be used to look for evidence of spread. These include computed tomography to evaluate spread within the pelvis, bone scans to look for spread to the bones, and endorectal coil magnetic resonance imaging to closely evaluate the prostatic capsule and the seminal vesicles. Bone scans should reveal osteoblastic appearance due to increased bone density in the areas of bone metastasis—opposite to what is found in many other cancers that metastasize.

Computed tomography (CT) and magnetic resonance imaging (MRI) currently do not add any significant information in the assessment of possible lymph node metastases in patients with prostate cancer according to a meta-analysis.^[5] The sensitivity of CT was 42% and specificity of CT was 82%. The sensitivity of MRI was 39% and the specificity of MRI was 82%. For patients at similar risk to those in this study (17% had positive pelvic lymph nodes in the CT studies and 30% had positive pelvic lymph nodes in the MRI studies), this leads to a positive predictive value (PPV) of 32.3% with CT, 48.1% with MRI, and negative predictive value (NPV) of 87.3% with CT, 75.8% with MRI.

After a prostate biopsy, a pathologist looks at the samples under a microscope. If cancer is present, the pathologist reports the grade of the tumor. The grade tells how much the tumor tissue differs from normal prostate tissue and suggests how fast the tumor is likely to grow. The Gleason system is used to grade prostate tumors from 2 to 10, where a Gleason score of 10 indicates the most abnormalities. The pathologist assigns a number from 1 to 5 for the most common pattern observed under the microscope, then does the same for the second-most-common pattern. The sum of these two numbers is the Gleason score. The Whitmore-Jewett stage is another method sometimes used. Proper grading of the tumor is critical, since the grade of the tumor is one of the major factors used to determine the treatment recommendation.^{[citation needed]}

Signs and symptoms

Early prostate cancer usually causes no symptoms. Often it is diagnosed during the workup for an elevated PSA noticed during a routine checkup. It's highly advised to avoid sexual intercourse for 3 days prior to a PSA test because that affects the outcome of the test. Sometimes, however, prostate cancer does cause symptoms, often similar to those of diseases such as benign prostatic hypertrophy. These include frequent urination, increased urination at night, difficulty starting and maintaining a steady stream of urine, blood in the urine, and painful urination. Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra. Changes within the gland, therefore, directly affect urinary function. Because the vas deferens deposits seminal fluid into the prostatic urethra, and secretions from the prostate gland itself are included in semen content, prostate cancer may also cause problems with sexual function and performance, such as difficulty achieving erection or painful ejaculation.^[6]

Advanced prostate cancer can spread to other parts of the body, possibly causing additional symptoms. The most common symptom is bone pain, often in the vertebrae (bones of the spine), pelvis, or ribs. Spread of cancer into other bones such as the femur is usually to the proximal part of the bone. Prostate cancer in the spine can also compress the spinal cord, causing leg weakness and urinary and fecal incontinence.^[7]

Causes

The specific causes of prostate cancer remain unknown.^[8] A man's risk of developing prostate cancer is related to his age, genetics, race, diet, lifestyle, medications, and other factors.^[9] The primary risk factor is age. Prostate cancer is very uncommon in men younger than 45, but becomes more common with advancing age. The average age at the time of diagnosis is 70.^[10] However, many men never know they have prostate cancer. Autopsy studies of Chinese, German, Israeli, Jamaican, Swedish, and Ugandan men who died of other causes have found prostate cancer in thirty percent of men in their 50s, and in eighty percent of men in their 70s.^[11] In the United States in 2005, there were an estimated 230,000 new cases of prostate cancer and 30,000 deaths due to prostate cancer.^[12] Men with high blood pressure are more likely to develop prostate cancer.^[13]

Genetics

Genetic background may contribute to prostate cancer risk, as suggested by associations with race, family, and specific gene variants. In the United States, prostate cancer more commonly affects black men than white or Hispanic men, and is also more deadly in black men.^[14][15] In contrast, the incidence and mortality rates for Hispanic men are one third lower than for non-Hispanic whites. Men who have a brother or father with prostate cancer have twice the risk of developing prostate cancer.^[16] Studies of twins in Scandinavia suggest that forty percent of prostate cancer risk can be explained by inherited factors.^[17]

No single gene is responsible for prostate cancer; many different genes have been implicated. Mutations in BRCA1 and BRCA2, important risk factors for ovarian cancer and breast cancer in women, have also been implicated in prostate cancer.^[18] Other linked genes include the "prostate cancer gene", HPC1, the androgen receptor, and the vitamin D receptor.^[19] The TEMPRSS2-ETS fusion gene exists in many prostate cancer cases and helps prostate cancer cells to survive and grow.^[20]

Diet

Evidence from epidemiological studies supports a possible protective role in reducing prostate cancer for dietary Vitamin B6,^[21] selenium, vitamin E, lycopene, and soy foods. A study in 2007 cast doubt on the effectiveness of lycopene (found in tomatoes) in reducing the risk of prostate cancer.^[22] Lower blood levels of vitamin D may increase the risk of developing prostate cancer.^[23] This may be linked to lower exposure to ultraviolet (UV) light, since UV light exposure can increase vitamin D in the body.^[24]

Studies comparing men who live in areas of the country with high levels of selenium to men in areas with low levels suggest that this mineral protects against prostate cancer.^[25] Selenium is believed to reduce the risk of developing prostate cancer because it keeps cells from proliferating or dying off in a rapid or unusual way. An analysis in 2002 of the Nutritional Prevention of Cancer Trial revealed that the men who took selenium supplements daily were half as likely to be diagnosed with prostate cancer.^[26] However, in 2008, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) indicated that neither selenium nor vitamin E, alone or in combination, was effective for the primary prevention of prostate cancer.^[27][28][29] Whether or not selenium helps prevent prostate cancer, researchers at the Dana-Farber Cancer Institute in Boston found that higher selenium levels in the blood may worsen prostate cancer in many men who already have the disease.^[29][30]

Green tea may be protective (due to its polyphenol content),^[31] although the most comprehensive clinical study indicates that it has no protective effect.^[32]

Research published in the Journal of the National Cancer Institute suggests that taking multivitamins more than seven times a week can increase the risks of contracting the disease.^[33][34] This research was unable to highlight the exact vitamins responsible for this increase (almost double), although they suggest that vitamin A, vitamin E and beta-carotene may lie at its heart. It is advised that those taking multivitamins never exceed the stated daily dose on the label.

A 2007 study published in the Journal of the National Cancer Institute found that men eating cauliflower, broccoli, or one of the other cruciferous vegetables, more than once a week were 40% less likely to develop prostate cancer than men who rarely ate those vegetables.^[35][36] The phytochemicals indole-3-carbinol and diindolylmethane, found in cruciferous vegetables, has antiandrogenic and immune modulating properties.^[37][38]

Many doctors prescribe supplements to prostate cancer patients but currently the efficacy of nutrient supplements is still unknown.^[39] Supplements may not be as beneficial to prostate health as micronutrients obatined naturally from the diet.^[39]

Folic acid supplements have recently been linked to an increase in risk of developing prostate cancer.^[40] A ten-year research study led by University of Southern California researchers showed that men who took daily folic acid supplements of 1 mg were three times more likely to be diagnosed with prostate cancer than men who took a placebo.^[40] Folate plays a complex role in prostate cancer and folic acid supplements have a different effect on prostate cancer than folate naturally found in foods.^[40] The supplement form, folic acid, is more bioavailable in the body compared with dietary sources of folate.^[40] Folate hydrolase activity is associated with prostate-specific antigen. A small Swedish study of 254 subjects, with a median age of 64, and a follow up of 5 years suggested that folate status is not protective against prostate cancer, however, and like folic acid may even result in a 3 fold increase in early prostate cancer development and risk.^[41] Supplements and multivitamins, alcohol and drug consumption, GI disorders, and folate bioavailability were not analyzed in this study.^[41]

High alcohol intake may increase the risk of prostate cancer and interfere with folate metabolism.^[42] Low folate intake and high alcohol intake may increase the risk of prostate cancer to a greater extent than the sole effect of either one by itself.^[42] A case control study consisting of 137 veterans addressed this hypothesis and the results were that high folate intake was related to a 79% lower risk of developing prostate cancer and there was no association between alcohol consumption by itself and prostate cancer risk.^[42] Folate's effect however was only significant when coupled with low alcohol intake.^[42] There is a significant decrease in risk of prostate cancer with increasing dietary folate intake but this association only remains in individuals with low levels of alcohol consumption.^[42] There was no association found in this study between folic acid supplements and risk of prostate cancer.^[42]

The prostate gland has a high concentration of zinc so it has been hypothesized that zinc plays a role in prostate cancer.^[43] Recently researchers studied the relationship between zinc supplement intake of 100 mg/day and the risk of prostate cancer in 46 974 US men over a 14 year period and found that long term zinc supplement intake may play a role in prostate carcinogenesis.^[43]

Medication exposure

There are also some links between prostate cancer and medications, medical procedures, and medical conditions. Daily use of anti-inflammatory medicines such as aspirin, ibuprofen, or naproxen may decrease prostate cancer risk.^[44] Use of the cholesterol-lowering drugs known as the statins may also decrease prostate cancer risk.^[45] Infection or inflammation of the prostate (prostatitis) may increase the chance for prostate cancer. In particular, infection with the sexually transmitted infections chlamydia, gonorrhea, or syphilis seems to increase risk.^[46] Finally, obesity^[47] and elevated blood levels of testosterone^[48] may increase the risk for prostate cancer. There is an association between vasectomy and prostate cancer however more research is needed to determine if this is a causative relationship.^[9]

Research released in May 2007, found that US war veterans who had been exposed to Agent Orange had a 48% increased risk of prostate cancer recurrence following surgery.^[49]

Potential viral cause

In 2006, researchers associated a previously unknown retrovirus, Xenotropic MuLV-related virus or XMRV, with human prostate tumors.^[50] Subsequent reports on the virus have been contradictory. A group of US researchers found XMRV protein expression in human prostate tumors,^[51] while German scientists failed to find XMRV-specific antibodies or XMRV-specific nucleic acid sequences in prostate cancer samples.^[52]

Pathophysiology

When normal cells are damaged beyond repair, they are eliminated by apoptosis. Cancer cells avoid apoptosis and continue to multiply in an unregulated manner.

Prostate cancer is classified as an adenocarcinoma, or glandular cancer, that begins when normal semen-secreting prostate gland cells mutate into cancer cells. The region of prostate gland where the adenocarcinoma is most common is the peripheral zone. Initially, small clumps of cancer cells remain confined to otherwise normal prostate glands, a condition known as carcinoma in situ or prostatic intraepithelial neoplasia (PIN). Although there is no proof that PIN is a cancer precursor, it is closely associated with cancer. Over time, these cancer cells begin to multiply and spread to the surrounding prostate tissue (the stroma) forming a tumor. Eventually, the tumor may grow large enough to invade nearby organs such as the seminal vesicles or the rectum, or the tumor cells may develop the ability to travel in the bloodstream and lymphatic system. Prostate cancer is considered a malignant tumor because it is a mass of cells that can invade other parts of the body. This invasion of other organs is called metastasis. Prostate cancer most commonly metastasizes to the bones, lymph nodes, rectum, and bladder. Runx2 is a transcription factor that prevents cancer cells from undergoing apoptosis thereby contributing to the development of prostate cancer.^[53] Tumor necrosis factor receptor-associated protein-1 (TRAP-1)is a mitochondrial protein that inhibits the apoptosis pathway and helps prostate cancer cells to survive and grow.^[54] The PI3k/Akt signaling cascade works with the transforming growth factor beta/SMAD signaling cascade to ensure prostate cancer cell survival and protection against apoptosis.^[55] X-linked inhibitor of apoptosis (XIAP) is hypothesized to promote prostate cancer cell survival and growth and is a target of research because if this inhibitor can be shut down then the apoptosis cascade can carry on its function in preventing cancer cell proliferation.^[56] Macrophage inhibitory cytokine-1 (MIC-1) stimulates the focal adhesion kinase (FAK) signaling pathway which leads to prostate cancer cell growth and survival.^[57] The androgen receptor helps prostate cancer cells to survive and is a target for many anti cancer research studies; so far, inhibiting the androgen receptor has only proven to be effective in mouse studies.^[58] Prostate specific membrane antigen (PSMA) stimulates the development of prostate cancer by increasing folate levels for the cancer cells to use to survive and grow; PSMA increases available folates for use by hydrolyzing glutamated folates.^[59]

Diagnosis

The only test that can fully confirm the diagnosis of prostate cancer is a biopsy, the removal of small pieces of the prostate for microscopic examination. However, prior to a biopsy, several other tools may be used to gather more information about the prostate and the urinary tract. Digital rectal examination may allow a doctor to detect prostate abnormalities. Cystoscopy shows the urinary tract from inside the bladder, using a thin, flexible camera tube inserted down the urethra. Transrectal ultrasonography creates a picture of the prostate using sound waves from a probe in the rectum.

Biopsy

Main article: Prostate biopsy

If cancer is suspected, a biopsy is offered. During a biopsy a urologist or radiologist obtains tissue samples from the prostate via the rectum. A biopsy gun inserts and removes special hollow-core needles (usually three to six on each side of the prostate) in less than a second. Prostate biopsies are routinely done on an outpatient basis and rarely require hospitalization. Fifty-five percent of men report discomfort during prostate biopsy.^[60]

Gleason score

Main article: Gleason score

The tissue samples are then examined under a microscope to determine whether cancer cells are present, and to evaluate the microscopic features (or Gleason score) of any cancer found. Prostate specific membrane antigen is a transmembrane carboxypeptidase and exhibits folate hydrolase activity.^[61] This protein is overexpressed in prostate cancer tissues and is associated with a higher Gleason score.^[61]

Tumor markers

Main article: Tumor markers

Tissue samples can be stained for the presence of PSA and other tumor markers in order to determine the origin of maligant cells that have metastasized.^[62] Small cell carcinoma is a type of prostate cancer that cannot be diagnosed using the PSA.^[63] Currently researchers are trying to determine the best way to screen for this type of prostate cancer because it is a relatively unknown and rare type of prostate cancer but very serious and quick to spread to other parts of the body.^[64]

Possible methods include chromatographic separation methods by mass spectrometry, or protein capturing by immunoassays or immunized antibodies. The test method will involve quantifying the amount of the biomarker PCI, with reference to the Gleason Score. Not only is this test quick, it is also sensitive. It can detect patients in the diagnostic grey zone, particularly those with a serum free to total Prostate Specific Antigen ratio of 10-20%.^[65]

Diagnostic tools under investigation

At present, an active area of research involves non-invasive methods of prostate tumor detection. Adenoviruses modified to transfect tumor cells with harmless yet distinct genes (such as luciferase) have proven capable of early detection. So far, however, this area of research has been tested only in animal and LNCaP models.^[66]

PCA3

Another potential non-invasive method of early prostate tumor detection is through a molecular test that detects the presence of cell-associated PCA3 mRNA in urine. PCA3 mRNA is expressed almost exclusively by prostate cells and has been shown to be highly over-expressed in prostate cancer cells. PCA3 is not a replacement for PSA but an additional tool to help decide whether, in men suspected of having prostate cancer, a biopsy is really needed. The higher the expression of PCA3 in urine, the greater the likelihood of a positive biopsy, i.e., the presence of cancer cells in the prostate.

Early prostate cancer

It was reported in April 2007 that a new blood test for early prostate cancer antigen-2 (EPCA-2) that may alert men if they have prostate cancer and how aggressive it will be is being researched.^[67][68] Thrombophlebitis is associated with an increased risk of prostate cancer and may be a good way for physicians to remind themselves to screen patients with thrombophlebitis for prostate cancer as well since these two are closely linked.^[69]

Prostate mapping

Prostate mapping is a method of diagnosis that may be accurate in determining the precise location and aggressiveness of a tumor. It uses a combination of multi-sequence MRI imaging techniques and a template-guided biopsy system, and involves taking multiple biopsies through the skin that lies in front of the rectum rather than through the rectum itself. The procedure is carried out under general anesthetic.^[70]

Prostasomes

Epithelial cells of the prostate secrete prostasomes as well as PSA. Prostasomes are membrane–surrounded, prostate-derived organelles that appear extracellularly, and one of their physiological functions is to protect the sperm from attacks by the female immune system. Cancerous prostate cells continue to synthesize and secrete prostasomes, and may be shielded against immunological attacks by these prostasomes. Research of several aspects of prostasomal involvement in prostate cancer has been performed.^[71]

Prevention

A comprehensive worldwide report Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective compiled by the World Cancer Research Fund and the American Institute for Cancer Research reports a significant relation between lifestyle (including food consumption) and cancer prevention. Other research also supports this finding.^[39] Exercise and diet may help prevent prostate cancer to the same extent as medications such as alpha-blockers and 5-alpha-reductase inhibitors.^[39] The potential role of diet in preventing prostate cancer is discussed in greater detail in the diet section of this article.

Two medications which block the conversion of testosterone to dihydrotestosterone, finasteride^[72] and dutasteride,^[73] have also shown some promise. The use of these medications for primary prevention is still in the testing phase, and they are not widely used for this purpose. The initial problem with these medications is that they may preferentially block the development of lower-grade prostate tumors, leading to a relatively greater chance of higher grade cancers, and negating any overall survival improvement. More recent research found that finasteride did not increase the percentage of higher grade cancers. A 2008 study update found that finasteride reduces the incidence of prostate cancer by 30%. In the original study it turns that that the smaller prostate caused by finasteride means that a doctor is more likely to hit upon cancer nests and more likely to find aggressive-looking cells. Most of the men in the study who had cancer — aggressive or not — chose to be treated and many had their prostates removed. A pathologist then carefully examined every one of those 500 prostates and compared the kinds of cancers found at surgery to those initially diagnosed at biopsy. Finasteride did not increase the risk of High-Grade prostate cancer.^[74][74]

Ejaculation frequency

More frequent ejaculation also may decrease a man's risk of prostate cancer. One study showed that men who ejaculated five times a week in their 20s had a decreased rate of prostate cancer, though other studies have shown no benefit.^[75][76] The results contradict those of previous studies, which have suggested that having had many sexual partners, or a high frequency of sexual activity, increases the risk of prostate cancer by up to 40 percent. The key difference is that these earlier studies defined sexual activity as sexual intercourse, whereas this study focused on the number of ejaculations, whether or not intercourse was involved.^[77] Another study completed in 2004 reported that "Most categories of ejaculation frequency were unrelated to risk of prostate cancer. However, high ejaculation frequency was related to decreased risk of total prostate cancer." The report abstract concluded, "Our results suggest that ejaculation frequency is not related to increased risk of prostate cancer."^[76] A 2008 study showed that men who engaged in frequent masturbation, of about two to seven times a week, at the ages of 20s and 30s, had a higher rate of prostate cancer, while men who engaged in frequent masturbation, once a week, at the age of 50s had a lower rate.^[78]

Oils and fatty acids

In experimental models using mice have been tested, dietary and serum omega-6 polyunsaturated fatty acids (PUFAs) increased prostate tumor growth,and has sped up histopathological progression, and decreased survival, while the omega-3 fatty acids, in the same situation, had the opposite, beneficial effect.^[79]

Men with high serum linoleic acid, but not palmitic, can reduce the risk of prostate cancer by taking tocopherol supplementation.^[80]

Men with elevated levels of long-chain omega-3 fatty acids (EPA and DHA) had lowered incidence.^[81]

A long-term study reports that "blood levels of trans fatty acids, in particular trans fats resulting from the hydrogenation of vegetable oils, are associated with an increased prostate cancer risk."^[82]

Some researchers have indicated that serum myristic acid^[80][83] and palmitic acid^[83] and dietary myristic^[84] and palmitic^[84] saturated fatty acids and serum palmitic combined with alpha-tocopherol supplementation^[80] are associated with increased risk of prostate cancer in a dose-dependent manner. Serum association of these and other saturated fatty acids was also investigated by another study.^[83]

The American Dietetic Association and Dieticians of Canada report a decreased incidence of prostate cancer for those following a vegetarian diet.^[85]

In lab tests on mice, prostate tumors grow slower with a no-carbohydrate diet.^[86][87]

Other

The membrane androgen receptor prevents prostate cancer cells from growing and surviving by stimulating the apoptosis cascade.^[88]

Screening

Main article: Prostate cancer screening

Prostate cancer screening is an attempt to find unsuspected cancers. Screening tests may lead to more specific follow-up tests such as a biopsy, where small cores of the prostate are removed for closer study. Prostate cancer screening options include the digital rectal exam and the prostate-specific antigen (PSA) blood test. Screening for prostate cancer is controversial because it is expensive and it is not at all clear whether the benefits of screening outweigh the risks of follow-up diagnostic tests and cancer treatments and the unnecessary worry for the patient that often ensues.^[89]

Prostate cancer is usually a slow-growing cancer, very common among older men. In fact, most prostate cancers never grow to the point where they cause symptoms, and most men with prostate cancer die of other causes before prostate cancer has an impact on their lives. The PSA screening test may detect these small cancers that would never become life-threatening. Doing the PSA test in these men may lead to overdiagnosis, including additional testing and treatment. Follow-up tests, such as prostate biopsy, may cause pain, bleeding and infection. Prostate cancer treatments may cause urinary incontinence and erectile dysfunction. A large randomized study in which 76,000 men were randomized to receive either PSA screening or conventional care found that more men that underwent PSA screening were diagnosed with prostate cancer, but that there was no difference in mortality between the two groups.^[90]

Management

Main article: Management of prostate cancer

Treatment for prostate cancer may involve active surveillance (monitoring for tumor progress or symptoms), surgery (i.e. radical prostatectomy), radiation therapy including brachytherapy (prostate brachytherapy) and external beam radiation therapy, High-intensity focused ultrasound (HIFU), chemotherapy, oral chemotherapeutic drugs (Temozolomide/TMZ), positron emission tomography, cryosurgery, hormonal therapy, or some combination.^[91][92][93] Which option is best depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors are the man's age, his general health, and his feelings about potential treatments and their possible side-effects. Because all treatments can have significant side-effects, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations. Prostate cancer patients are strongly recommended to work closely with their urologist and use a combination of the treatment options when managing their prostate cancer.^[94][95]

The selection of treatment options may be a complex decision involving many factors. For example, radical prostatectomy after primary radiation failure is a very technically challenging surgery and may not be an option.^[96] This may enter into the treatment decision.

If the cancer has spread beyond the prostate, treatment options significantly change, so most doctors that treat prostate cancer use a variety of nomograms to predict the probability of spread. Treatment by watchful waiting/active surveillance, HIFU, external beam radiation therapy, brachytherapy, cryosurgery, and surgery are, in general, offered to men whose cancer remains within the prostate. Hormonal therapy and chemotherapy are often reserved for disease that has spread beyond the prostate. However, there are exceptions: radiation therapy may be used for some advanced tumors, and hormonal therapy is used for some early stage tumors. Cryotherapy (the process of freezing the tumor), hormonal therapy, and chemotherapy may also be offered if initial treatment fails and the cancer progresses.^[97]

Prostate cancer can be treated by using Ad.DD3-E1A-IL-24 which stimulates apoptosis in cancer cells thereby inhibiting tumor growth.^[98]

Prognosis

Prostate cancer rates are higher and prognosis poorer in developed countries than the rest of the world. Many of the risk factors for prostate cancer are more prevalent in the developed world, including longer life expectancy and diets high in red meat and reduced-fat dairy products to which vitamin A palmitate has been added.^[99] (People that consume larger amounts of meat and dairy also tend to consume fewer portions of fruits and vegetables. It is not currently clear whether both of these factors, or just one of them, contribute to the occurrence of prostate cancer.^[100]) Also, where there is more access to screening programs, there is a higher detection rate. Prostate cancer is the ninth-most-common cancer in the world, but is the number-one non-skin cancer in United States men. Prostate cancer affected eighteen percent of American men and caused death in three percent in 2005.^[101] In Japan, death from prostate cancer was one-fifth to one-half the rates in the United States and Europe in the 1990s.^[102] In India in the 1990s, half of the people with prostate cancer confined to the prostate died within ten years.^[103] African-American men have 50–60 times more prostate cancer and prostate cancer deaths than men in Shanghai, China.^[104] In Nigeria, two percent of men develop prostate cancer and 64% of them are dead after two years.^[105]

In patients that undergo treatment, the most important clinical prognostic indicators of disease outcome are stage, pre-therapy PSA level and Gleason score. In general, the higher the grade and the stage the poorer the prognosis. Nomograms can be used to calculate the estimated risk of the individual patient. The predictions are based on the experience of large groups of patients suffering from cancers at various stages.^[106]

In 1941, Charles Huggins reported that androgen ablation therapy causes regression of primary and metastatic androgen-dependent prostate cancer.^[107] Androgen ablation therapy causes remission in 80-90% of patients undergoing therapy, resulting in a median progression-free survival of 12 to 33 months. After remission, an androgen-independent phenotype typically emerges, wherein the median overall survival is 23–37 months from the time of initiation of androgen ablation therapy.^[108] The actual mechanism contributes to the progression of prostate cancer is not clear and may vary between individual patient. A few possible mechanisms have been proposed.^[109] Androgen at a concentration of 10-fold higher than the physiological concentration has also been shown to cause growth suppression and reversion of androgen-independent prostate cancer xenografts or androgen-independent prostate tumors derived in vivo model to an androgen-stimulated phenotype in athymic mice.^[110][111] These observation suggest the possibility to use androgen to treat the development of relapsed androgen-independent prostate tumors in patients. Oral infusion of green tea polyphenols, a potential alternative therapy for prostate cancer by natural compounds, has been shown to inhibit the development, progression, and metastasis as well in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which spontaneously develops prostate cancer.^[112]

Classification systems

Many prostate cancers are not destined to be lethal, and most men will ultimately die from causes other than of the disease. Decisions about treatment type and timing may, therefore, be informed by an estimation of the risk that the tumor will ultimately recur after treatment and/or progress to metastases and mortality. Several tools are available to help predict outcomes such as pathologic stage and recurrence after surgery or radiation therapy. Most combine stage, grade, and PSA level, and some also add the number or percent of biopsy cores positive, age, and/or other information.

• The D’Amico classification stratifies men by low, intermediate, or high risk based on stage, grade, and PSA. It is used widely in clinical practice and research settings. The major downside to the 3-level system is that it does not account for multiple adverse parameters (e.g., high Gleason score and high PSA) in stratifying patients.

• The Partin tables predict pathologic outcomes (margin status, extraprostatic extension, and seminal vesicle invasion) based on the same 3 variables, and are published as lookup tables.

• The Kattan nomograms predict recurrence after surgery and/or radiation therapy, based on data available either at time of diagnosis or after surgery. The nomograms can be calculated using paper graphs, or using software available on a website or for handheld computers. The Kattan score represents the likelihood of remaining free of disease at a given time interval following treatment.

• The UCSF Cancer of the Prostate Risk Assessment (CAPRA) score predicts both pathologic status and recurrence after surgery. It offers comparable accuracy as the Kattan preoperative nomogram, and can be calculated without paper tables or a calculator. Points are assigned based on PSA, Grade, stage, age, and percent of cores positive; the sum yields a 0–10 score, with every 2 points representing roughly a doubling of risk of recurrence. The CAPRA score was derived from community-based data in the CaPSURE database. It has been validated among over 10,000 prostatectomy patients, including patients from CaPSURE^[113]; the SEARCH registry, representing data from several Veterans Administration and active military medical centers^[114]; a multi-institutional cohort in Germany^[115]; and the prostatectomy cohort at Johns Hopkins University.^[116] More recently, it has been shown to predict metastasis and mortality following prostatectomy, radiation therapy, watchful waiting, or androgen deprivation therapy.^[117]

Epidemiology

Age-standardized death from prostate cancer per 100,000 inhabitants in 2004.^[118]

     no data      less than 4      4-8      8-12      12-16      16-20      20-24      24-28      28-32      32-36      36-40      40-44      more than 44

Rates of prostate cancer vary widely across the world. Although the rates vary widely between countries, it is least common in South and East Asia, more common in Europe, and most common in the United States.^[1] According to the American Cancer Society, prostate cancer is least common among Asian men and most common among black men, with figures for white men in between.^[119][120] However, these high rates may be affected by increasing rates of detection.^[121]

Prostate cancer develops primarily in men over fifty. It is the most common type of cancer in men in the United States, with 186,000 new cases in 2008 and 28,600 deaths.^[122] Prostate cancer is also the most common cancer among Canadian men.^{[citation needed]} It is the second leading cause of cancer death in U.S. men after lung cancer. In the United Kingdom it is also the second most common cause of cancer death after lung cancer, where around 35,000 cases are diagnosed every year and of which around 10,000 die of it. Many factors, including genetics and diet, have been implicated in the development of prostate cancer. The Prostate Cancer Prevention Trial found that finasteride reduces the incidence of prostate cancer rate by 30%. There had been a controversy about this also increasing the risk of more aggressive cancers, but more recent research showed this may not be the case.^[74][123]

History

Although the prostate was first described by Venetian anatomist Niccolò Massa in 1536, and illustrated by Flemish anatomist Andreas Vesalius in 1538, prostate cancer was not identified until 1853.^[124] Prostate cancer was initially considered a rare disease, probably because of shorter life expectancies and poorer detection methods in the 19th century. The first treatments of prostate cancer were surgeries to relieve urinary obstruction.^[125] Removal of the entire gland (radical perineal prostatectomy) was first performed in 1904 by Hugh H. Young at Johns Hopkins Hospital.^[126] Surgical removal of the testes (orchiectomy) to treat prostate cancer was first performed in the 1890s, but with limited success. Transurethral resection of the prostate (TURP) replaced radical prostatectomy for symptomatic relief of obstruction in the middle of the 20th century because it could better preserve penile erectile function. Radical retropubic prostatectomy was developed in 1983 by Patrick Walsh.^[127] This surgical approach allowed for removal of the prostate and lymph nodes with maintenance of penile function.

In 1941, Charles B. Huggins published studies in which he used estrogen to oppose testosterone production in men with metastatic prostate cancer. This discovery of "chemical castration" won Huggins the 1966 Nobel Prize in Physiology or Medicine.^[128] The role of the hormone GnRH in reproduction was determined by Andrzej W. Schally and Roger Guillemin, who both won the 1977 Nobel Prize in Physiology or Medicine for this work.

Receptor agonists, such as leuprolide and goserelin, were subsequently developed and used to treat prostate cancer.^[129][130]

Radiation therapy for prostate cancer was first developed in the early 20th century and initially consisted of intraprostatic radium implants. External beam radiation became more popular as stronger radiation sources became available in the middle of the 20th century. Brachytherapy with implanted seeds was first described in 1983.^[131] Systemic chemotherapy for prostate cancer was first studied in the 1970s. The initial regimen of cyclophosphamide and 5-fluorouracil was quickly joined by multiple regimens using a host of other systemic chemotherapy drugs.^[132]

Research

The insulin-like growth factor signaling axis is thought to play a key role in the progression of prostate carcinoma. It consists of two ligands (IGF-1 and IGF-2), two receptors (IGF-IR and IGF-IIR) and six related high-affinity IGF-binding proteins (IGFBP 1-6).^[133] Altered expression of IGF axis members has been implicated in the development of many different types of cancers, including prostate.^[134][135]

Prostate cancer models

Scientists have established a few prostate cancer cell lines to investigate the mechanism involved in the progression of prostate cancer. LNCaP, PC-3 (PC3), and DU-145 (DU145) are commonly used prostate cancer cell lines. The LNCaP cancer cell line was established from a human lymph node metastatic lesion of prostatic adenocarcinoma. PC-3 and DU-145 cells were established from human prostatic adenocarcinoma metastatic to bone and to brain, respectively. LNCaP cells express androgen receptor (AR); however, PC-3 and DU-145 cells express very little or no AR. AR, an androgen-activated transcription factor, belongs to the steroid nuclear receptor family. Development of the prostate is dependent on androgen signaling mediated through AR, and AR is also important during the development of prostate cancer. The proliferation of LNCaP cells is androgen-dependent but the proliferation of PC-3 and DU-145 cells is androgen-insensitive. Elevation of AR expression is often observed in advanced prostate tumors in patients.^[136][137] Some androgen-independent LNCaP sublines have been developed from the ATCC androgen-dependent LNCaP cells after androgen deprivation for study of prostate cancer progression. These androgen-independent LNCaP cells have elevated AR expression and express prostate specific antigen upon androgen treatment. The paradox is that androgens inhibit the proliferation of these androgen-independent prostate cancer cells.^{[138][139][140]}

See also

	Book:Prostate
Books are collections of articles which can be downloaded or ordered in print.

References

1. ^ ^{a b} "IARC Worldwide Cancer Incidence Statistics—Prostate". JNCI Cancer Spectrum. Oxford University Press. December 19, 2001. http://web.archive.org/web/20060205235509/http://www.jncicancerspectrum.oxfordjournals.org/cgi/statContent/cspectfstat;99.  Retrieved on 5 April 2007 through the Internet Archive
2. ^ Aumüller, G. (1979). Prostate Gland and Seminal Vesicles. Berlin-Heidecool.lberg: Springer-Verlag. 
3. ^ Moore, K.; Dalley, A. (1999). Clinically Oriented Anatomy. Baltimore, Maryland: Lippincott Williams & Wilkins. 
4. ^ Steive, H. (1930). "Männliche Genitalorgane". Handbuch der mikroskopischen Anatomie des Menschen. Vol. VII Part 2. Berlin: Springer. pp. 1–399. 
5. ^ Smith JA, Chan RC, Chang SS, et al. (2007). "A comparison of the incidence and location of positive surgical margins in robotic assisted laparoscopic radical prostatectomy and open retropubic radical prostatectomy". J. Urol. 178 (6): 2385–9; discussion 2389–90. doi:10.1016/j.juro.2007.08.008. PMID 17936849. 
6. ^ Miller DC, Hafez KS, Stewart A, Montie JE, Wei JT (September 2003). "Prostate carcinoma presentation, diagnosis, and staging: an update form the National Cancer Data Base". Cancer 98 (6): 1169–78. doi:10.1002/cncr.11635. PMID 12973840. 
7. ^ van der Cruijsen-Koeter, IW; Vis AN, Roobol MJ, Wildhagen MF, de Koning HJ, van der Kwast TH, Schroder FH (July 2005). "Comparison of screen detected and clinically diagnosed prostate cancer in the European randomized study of screening for prostate cancer, section rotterdam". Urol 174 (1): 121–5. doi:10.1097/01.ju.0000162061.40533.0f. PMID 15947595. 
8. ^ Hsing AW, Chokkalingam AP (2006). "Prostate cancer epidemiology". Frontiers in Bioscience 11: 1388–413. doi:10.2741/1891. PMID 16368524. 
9. ^ ^{a b} http://www.bccancer.bc.ca
10. ^ Hankey, BF; Feuer EJ, Clegg LX, Hayes RB, Legler JM, Prorok PC, Ries LA, Merrill RM, Kaplan RS (June 16 1999). "Cancer surveillance series: interpreting trends in prostate cancer—part I: Evidence of the effects of screening in recent prostate cancer incidence, mortality, and survival rates". J Natl Cancer Inst 91 (12): 1017–24. doi:10.1093/jnci/91.12.1017. PMID 10379964. 
11. ^ Breslow, N; Chan CW, Dhom G, Drury RA, Franks LM, Gellei B, Lee YS, Lundberg S, Sparke B, Sternby NH, Tulinius H. (November 15 1977). "Latent carcinoma of prostate at autopsy in seven areas. The International Agency for Research on Cancer, Lyons, France". Int J Cancer 20 (5): 680–8. doi:10.1002/ijc.2910200506. PMID 924691. 
12. ^ Jemal A, A; Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ (Jan-February 2005). "Cancer statistics, 2005". CA Cancer J Clin 55 (1): 10–30. doi:10.3322/canjclin.55.1.10. PMID 15661684.  Erratum in: CA Cancer J Clin. 2005 Jul-Aug;55(4):259
13. ^ Martin RM, Vatten L, Gunnell D, Romundstad P. Cancer Causes Control. 2009 Dec 1. Blood pressure and risk of prostate cancer: cohort Norway (CONOR).
14. ^ Richard P. Gallagher, PhD; Neil Fleshner, MD (1998). "Prostate cancer: 3. Individual risk factors". Canadian Medical Association Journal Oct 6: 807–13. http://www.cmaj.ca/cgi/reprint/159/7/807.pdf. 
15. ^ Hoffman, RM; Gilliland FD; Eley JW; Harlan LC; Stephenson RA; Stanford JL; Albertson PC; Hamilton AS; Hunt WC; Potosky AL (March 7 2001). "Racial and ethnic differences in advanced-stage prostate cancer: the Prostate Cancer Outcomes Study". J Natl Cancer Inst 93 (5): 388–95. doi:10.1093/jnci/93.5.388. PMID 11238701. 
16. ^ Steinberg, GD; Carter BS; Beaty TH; Childs B; Walsh PC (1990). "Family history and the risk of prostate cancer". Prostate 17 (4): 337–47. doi:10.1002/pros.2990170409. PMID 2251225. 
17. ^ Lichtenstein, P; Holm NV; Verkasalo PK; Iliadou A; Kaprio J; Koskenvuo M; Pukkala E; Skytthe A; Hemminki K (July 13 2000). "Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland". N Engl J Med 343 (2): 78–85. doi:10.1056/NEJM200007133430201. PMID 10891514. 
18. ^ Struewing, JP; Hartge P; Wacholder S; Baker SM; Berlin M; McAdams M; Timmerman MM; Brody LC; Tucker MA (May 15 1997). "The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews". N Engl J Med 336 (20): 1401–8. doi:10.1056/NEJM199705153362001. PMID 9145676. 
19. ^ [1]
20. ^ Beuzeboc P, Soulié M, Richaud P, Salomon L, Staerman F, Peyromaure M, Mongiat-Artus P, Cornud F, Paparel P, Davin JL, Molinié V. Prog Urol. 2009 Dec;19(11):819-24. Epub 2009 Jul 16. Fusion genes and prostate cancer. From discovery to prognosis and therapeutic perspectives.
21. ^ Kasperzyk JL et al., One-carbon metabolism-related nutrients and prostate cancer survival. Am J Clin Nutr. 2009 Sep;90(3):561-9.
22. ^ Peters U, Leitzmann MF, Chatterjee N, Wang Y, Albanes D, Gelmann EP, Friesen MD, Riboli E, Hayes RB (2007). "Serum lycopene, other carotenoids, and prostate cancer risk: a nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial". Cancer Epidemiol. Biomarkers Prev. 16 (5): 962–8. doi:10.1158/1055-9965.EPI-06-0861. PMID 17507623. http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17507623. Retrieved 17 December 2007. 
23. ^ Wigle DT, Turner MC, Gomes J, Parent ME (March 2008). "Role of hormonal and other factors in human prostate cancer". Journal of Toxicology and Environmental Health. Part B, Critical Reviews 11 (3-4): 242–59. doi:10.1080/10937400701873548. PMID 18368555. 
24. ^ Schulman, CC; Ekane S; Zlotta AR (September 2001). "Nutrition and prostate cancer: evidence or suspicion?". Urology 58 (3): 318–34. doi:10.1016/S0090-4295(01)01262-6. PMID 11549473. 
25. ^ Brinkman M, Reulen RC, Kellen E, Buntinx F, & Zeegers MP (2006). "Are men with low selenium levels at increased risk of prostate cancer?". European Journal of Cancer 42: 2463–2471. 
26. ^ Duffield-Lillico AJ, et al. (2002). "Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: A summary report of the Nutritional Prevention of Cancer Trial". Cancer Epidemiology, Biomarkers, and Prevention 11: 630–693. 
27. ^ Lippman SM, et al. (2008). "Effect of selenium and vitamin E on risk of prostate cancer and other cancers: The Selenium and Vitamin E Cancer Prevention Trial (SELECT)". Journal of American Medical Association 301: 39–51. 
28. ^ Klein EA, et al. (2001). "SELECT: The next prostate cancer prevention trial-Selenium and Vitamin E Cancer Prevention Trial.". Journal of Urology 166: 1311–1315. 
29. ^ ^{a b} Portes-Antoine S., & France de Bravo B. (August 2009). "Prostate Cancer: Diet and Dietary Supplements". Cancer Prevention and Treatment Fund. http://www.stopcancerfund.org/posts/207. Retrieved January 12, 2010. 
30. ^ Chan JM et al. (2009). "Plasma Selenium, Manganese Superoxide Dismutase, and Intermediate-or High-Risk Prostate Cancer". Journal of Clinical Oncology 27: 3577–3583. 
31. ^ Lee AH, Fraser ML, Meng X, Binns CW (April 2006). "Protective effects of green tea against prostate cancer". Expert Rev Anticancer Ther 6 (4): 507–13. doi:10.1586/14737140.6.4.507. PMID 16613539. 
32. ^ Kikuchi N, Ohmori K, Shimazu T, et al. (August 2006). "No association between green tea and prostate cancer risk in Japanese men: the Ohsaki Cohort Study". British Journal of Cancer 95 (3): 371–3. doi:10.1038/sj.bjc.6603230. PMID 16804523. 
33. ^ "Multivitamin prostate warning". Health. BBC NEWS. 16 May 2007. http://news.bbc.co.uk/1/hi/health/6657795.stm. Retrieved 23 April 2008. 
34. ^ Lawson KA, Wright ME, Subar A, Mouw T, Hollenbeck A, Schatzkin A, Leitzmann MF (May 2007). "Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study". J. Natl. Cancer Inst. 99 (10): 754–64. doi:10.1093/jnci/djk177. PMID 17505071. 
35. ^ "Broccoli May Help Cut Prostate Cancer, Broccoli, Cauliflower May Make Aggressive Prostate Cancer Less Likely". CBS News. 24 July 2007. http://www.cbsnews.com/stories/2007/07/24/health/webmd/main3094509.shtml. Retrieved 23 April 2008. 
36. ^ Kirsh VA, Peters U, Mayne ST, Subar AF, Chatterjee N, Johnson CC, Hayes RB (August 2007). "Prospective study of fruit and vegetable intake and risk of prostate cancer". J. Natl. Cancer Inst. 99 (15): 1200–9. doi:10.1093/jnci/djm065. PMID 17652276. 
37. ^ Sarkar FH, Li Y (December 2004). "Indole-3-carbinol and prostate cancer". J. Nutr. 134 (12 Suppl): 3493S–3498S. PMID 15570059. 
38. ^ Hsu JC, Zhang J, Dev A, Wing A, Bjeldanes LF, Firestone GL (November 2005). "Indole-3-carbinol inhibition of androgen receptor expression and downregulation of androgen responsiveness in human prostate cancer cells". Carcinogenesis 26 (11): 1896–904. doi:10.1093/carcin/bgi155. PMID 15958518. http://carcin.oxfordjournals.org/cgi/content/full/26/11/1896. Retrieved 12 September 2008. 
39. ^ ^{a b c d} Poon KS, McVary KT. Curr Urol Rep. 2009 Jul;10(4):279-86. Dietary patterns, supplement use, and the risk of benign prostatic hyperplasia.
40. ^ ^{a b c d} Figueiredo JC, Grau MV, Haile RW, et al. (March 2009). "Folic acid and risk of prostate cancer: results from a randomized clinical trial". Journal of the National Cancer Institute 101 (6): 432–5. doi:10.1093/jnci/djp019. PMID 19276452. 
41. ^ ^{a b} Hultdin J, Van Guelpen B, Bergh A, Hallmans G, Stattin P (February 2005). "Plasma folate, vitamin B12, and homocysteine and prostate cancer risk: a prospective study". International Journal of Cancer 113 (5): 819–24. doi:10.1002/ijc.20646. PMID 15499634. 
42. ^ ^{a b c d e f} Folate nutrition, alcohol consumption, and prostate cancer risk: A case-control study. 2006 Phoutrides E et al
43. ^ ^{a b} Leitzmann MF et al Journal of the National Cancer Institute 2003 95(13):1004-1007, Zinc Supplement Use and Risk of Prostate Cancer
44. ^ Jacobs EJ, Rodriguez C, Mondul AM, et al. (July 2005). "A large cohort study of aspirin and other nonsteroidal anti-inflammatory drugs and prostate cancer incidence". Journal of the National Cancer Institute 97 (13): 975–80. doi:10.1093/jnci/dji173. PMID 15998950. 
45. ^ Shannon, J; Tewoderos S, Garzotto M, Beer TM, Derenick R, Palma A, Farris PE (August 15 2005). "Statins and prostate cancer risk: a case-control study". Am J Epidemiol 162 (4): 318–25. doi:10.1093/aje/kwi203. PMID 16014776.  Epub 2005 July 13
46. ^ Dennis, LK; Lynch CF; Torner JC (July 2002). "Epidemiologic association between prostatitis and prostate cancer". Urology 60 (1): 78–83. doi:10.1016/S0090-4295(02)01637-0. PMID 12100928. 
47. ^ Calle, EE; Rodriguez C, Walker-Thurmond K, Thun MJ (April 24 2003). "Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults". N Engl J Med 348 (17): 1625–38. doi:10.1056/NEJMoa021423. PMID 12711737. 
48. ^ Gann, PH; Hennekens CH, Ma J, Longcope C, Stampfer MJ (August 21 1996). "Prospective study of sex hormone levels and risk of prostate cancer". J Natl Cancer Inst 88 (16): 1118–26. doi:10.1093/jnci/88.16.1118. PMID 8757191. 
49. ^ "Veterans exposed to Agent Orange have higher rates of prostate cancer recurrence". Medical College of Georgia News. May 20, 2007. https://my.mcg.edu/portal/page/portal/News/archive/2007/Veterans%20exposed%20to%20Agent%20%20Orange%20have%20higher%20rates%20of%20prost. 
50. ^ Urisman A, Molinaro RJ, Fischer N, et al. (March 2006). "Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant". PLoS Pathogens 2 (3): e25. doi:10.1371/journal.ppat.0020025. PMID 16609730. 
51. ^ Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR (September 2009). "XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors". Proceedings of the National Academy of Sciences of the United States of America 106 (38): 16351–6. doi:10.1073/pnas.0906922106. PMID 19805305. 
52. ^ Hohn O, Krause H, Barbarotto P, et al. (2009). "Lack of evidence for xenotropic murine leukemia virus-related virus(XMRV) in German prostate cancer patients". Retrovirology 6: 92. doi:10.1186/1742-4690-6-92. PMID 19835577. 
53. ^ Lim M, Zhong C, Yang S, Bell AM, Cohen MB, Roy-Burman P. Lab Invest. 2009 Nov 30. Runx2 regulates survivin expression in prostate cancer cells.
54. ^ Leav I, Plescia J, Goel HL, Li J, Jiang Z, Cohen RJ, Languino LR, Altieri DC. Am J Pathol. 2009 Nov 30. Cytoprotective Mitochondrial Chaperone TRAP-1 As a Novel Molecular Target in Localized and Metastatic Prostate Cancer.
55. ^ Zha J, Huang YF. Zhonghua Nan Ke Xue. 2009 Sep;15(9):840-3. TGF-beta/Smad in prostate cancer: an update.
56. ^ Watanabe SI, Miyata Y, Kanda S, Iwata T, Hayashi T, Kanetake H, Sakai H. J Cancer Res Clin Oncol. 2009 Nov 28.Expression of X-linked inhibitor of apoptosis protein in human prostate cancer specimens with and without neo-adjuvant hormonal therapy.
57. ^ Senapati S, Rachagani S, Chaudhary K, Johansson SL, Singh RK, Batra SK. Oncogene. 2009 Nov 30. Overexpression of macrophage inhibitory cytokine-1 induces metastasis of human prostate cancer cells through the FAK-RhoA signaling pathway.
58. ^ Narizhneva NV, Tararova ND, Ryabokon P, Shyshynova I, Prokvolit A, Komarov PG, Purmal AA, Gudkov AV, Gurova KV. Cell Cycle. 2009 Dec 13;8(24). Small molecule screening reveals a transcription-independent pro-survival function of androgen receptor in castration-resistant prostate cancer.
59. ^ Yao V, Berkman CE, Choi JK, O'Keefe DS, Bacich DJ. Prostate. 2009 Oct 14. Expression of prostate-specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non-polyglutamated folate, folic acid.
60. ^ Essink-Bot, ML; de Koning HJ, Nijs HG, Kirkels WJ, van der Maas PJ, Schroder FH (June 17 1998). "Short-term effects of population-based screening for prostate cancer on health-related quality of life". J Natl Cancer Inst 90 (12): 925–31. doi:10.1093/jnci/90.12.925. PMID 9637143. 
61. ^ ^{a b} figueiredo et al 2009 folic acid and risk or prostate cancer: results from a randomized clinical trial
62. ^ Chuang AY, Demarzo AM, Veltri RW, Sharma RB, Bieberich CJ, Epstein JI (2007). "Immunohistochemical Differentiation of High-grade Prostate Carcinoma From Urothelial Carcinoma". The American Journal of Surgical Pathology 31 (8): 1246–1255. doi:10.1097/PAS.0b013e31802f5d33. PMID 17667550. 
63. ^ Wei ZF, Xu H, Wang H, Wei W, Cheng W, Zhou WQ, Ge JP, Zhang ZY, Gao JP, Yin HL. Zhonghua Nan Ke Xue. 2009 Sep;15(9):829-32. Clinicopathological characterization of prostatic small cell carcinoma: a case report and review of the literature.
64. ^ Wei ZF, Xu H, Wang H, Wei W, Cheng W, Zhou WQ, Ge JP, Zhang ZY, Gao JP, Yin HL. Zhonghua Nan Ke Xue. 2009 Sep;15(9):829-32. Clinicopathological characterization of prostatic small cell carcinoma: a case report and review of the literature.
65. ^ [2]
66. ^ Iyer M, Salazar FB, Lewis X, Zhang L, Wu L, Carey M and Gambhir SS. Non-invasive imaging of a transgenic mouse model using a prostate-specific two-step transcriptional amplification strategy. Transg Res.2005; 14(1): 47–55
67. ^ A Prostate Cancer Revolution. Newsweek, April 26, 2007.
68. ^ Hansel DE, DeMarzo AM, Platz EA, et al. (2007). "Early prostate cancer antigen expression in predicting presence of prostate cancer in men with histologically negative biopsies". J. Urol. 177 (5): 1736–40. doi:10.1016/j.juro.2007.01.013. PMID 17437801. 
69. ^ van Weert HC, Pingen F. Cases J. 2009 Oct 13;2:153. Recurrent thromboflebitis as a warning sign for cancer: a case report.
70. ^ Sartor AO, Hricak H, Wheeler TM, et al. (December 2008). "Evaluating localized prostate cancer and identifying candidates for focal therapy". Urology 72 (6 Suppl): S12–24. doi:10.1016/j.urology.2008.10.004. PMID 19095124. 
71. ^ Ronquist G, Carlsson L, Larsson A, Nilsson BO: "Prostasomes: Proceedings from a symposium held at the Wenner-Gren Centre, Stockholm, June 2001" pp. 1-9. Portland Press , London
72. ^ Thompson IM, Goodman PJ, Tangen CM, et al. (July 2003). "The influence of finasteride on the development of prostate cancer". The New England Journal of Medicine 349 (3): 215–24. doi:10.1056/NEJMoa030660. PMID 12824459. 
73. ^ Andriole GL, Roehrborn C, Schulman C, Slawin KM, Somerville M, Rittmaster RS (September 2004). "Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia". Urology 64 (3): 537–41; discussion 542–3. doi:10.1016/j.urology.2004.04.084. PMID 15351586. 
74. ^ ^{a b c} Redman MW, Tangen CM, Goodman PJ, Lucia MS, Coltman CA, Thompson IM (August 2008). "Finasteride does not increase the risk of high-grade prostate cancer: a bias-adjusted modeling approach". Cancer Prevention Research 1 (3): 174–81. doi:10.1158/1940-6207.CAPR-08-0092. PMID 19138953. 
75. ^ Giles GG, Severi G, English DR, et al. (August 2003). "Sexual factors and prostate cancer". BJU International 92 (3): 211–6. doi:10.1046/j.1464-410X.2003.04319.x. PMID 12887469. 
76. ^ ^{a b} Leitzmann MF, Platz EA, Stampfer MJ, Willett WC, Giovannucci E (April 2004). "Ejaculation frequency and subsequent risk of prostate cancer". JAMA 291 (13): 1578–86. doi:10.1001/jama.291.13.1578. PMID 15069045. 
77. ^ Douglas Fox (16 July 2003). "Masturbating may protect against prostate cancer". New Scientist. http://www.newscientist.com/article/dn3942-masturbating-may-protect-against-prostate-cancer.html. Retrieved 23 April 2008. 
78. ^ Dimitropoulou P, Lophatananon A, Easton D, et al. (January 2009). "Sexual activity and prostate cancer risk in men diagnosed at a younger age". BJU International 103 (2): 178–85. doi:10.1111/j.1464-410X.2008.08030.x. PMID 19016689. 
79. ^ Berquin IM, Min Y, Wu R, et al. (July 2007). "Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids". The Journal of Clinical Investigation 117 (7): 1866–75. doi:10.1172/JCI31494. PMID 17607361. 
80. ^ ^{a b c} Männistö S, Pietinen P, Virtanen MJ, et al. (December 2003). "Fatty acids and risk of prostate cancer in a nested case-control study in male smokers". Cancer Epidemiology, Biomarkers & Prevention 12 (12): 1422–8. PMID 14693732. http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=14693732. 
81. ^ Gann, PH and Giovannucci (2005). "Prostate Cancer and Nutrition" (PDF). http://www.prostatecancerfoundation.org/atf/cf/%7B705B3273-F2EF-4EF6-A653-E15C5D8BB6B1%7D/Nutrition_Guide.pdf. Retrieved February 20, 2006.  in .pdf format.
82. ^ Chavarro et al., "A prospective study of blood trans fatty acid levels and risk of prostate cancer," Proc. Amer. Assoc. Cancer Res., Volume 47, 2006 [3].
83. ^ ^{a b c} Crowe FL, Allen NE, Appleby PN, et al. (November 2008). "Fatty acid composition of plasma phospholipids and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition". The American Journal of Clinical Nutrition 88 (5): 1353–63. PMID 18996872. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=18996872. 
84. ^ ^{a b} Kurahashi N, Inoue M, Iwasaki M, Sasazuki S, Tsugane AS (April 2008). "Dairy product, saturated fatty acid, and calcium intake and prostate cancer in a prospective cohort of Japanese men". Cancer Epidemiology, Biomarkers & Prevention 17 (4): 930–7. doi:10.1158/1055-9965.EPI-07-2681. PMID 18398033. 
85. ^ American Dietetic Association and Dieticians of Canada (June 2003). "Position of the American Dietetic Association and Dietitians of Canada: Vegetarian diets". Journal of the American Dietetic Association 103 (6): 748–65. doi:10.1053/jada.2003.50142. PMID 12778049. 
86. ^ No-Carb Diet May Curb Prostate Cancer
87. ^ Freedland SJ, Mavropoulos J, Wang A, Darshan M, Demark-Wahnefried W, Aronson WJ, Cohen P, Hwang D, Peterson B, Fields T, Pizzo SV, Isaacs WB. "Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis". Prostate. 2008 Jan 1;68(1):11-9. doi:10.1002/pros.20683. PMID 17999389.
88. ^ Gu S, Papadopoulou N, Gehring EM, et al. (December 2009). "Functional membrane androgen receptors in colon tumors trigger pro-apoptotic responses in vitro and reduce drastically tumor incidence in vivo". Molecular Cancer 8 (1): 114. doi:10.1186/1476-4598-8-114. PMID 19948074. 
89. ^ Collins, M. M., Barry, M. J. (1996). Controversies in Prostate Cancer Screening: Analogies to the Early Lung Cancer Screening Debate. JAMA 276: 1976-1979
90. ^ Andriole GL, Crawford ED, Grubb RL, et al. (March 2009). "Mortality results from a randomized prostate-cancer screening trial". The New England Journal of Medicine 360 (13): 1310–9. doi:10.1056/NEJMoa0810696. PMID 19297565. 
91. ^ Hong H, Zhang Y, Sun J, Cai W. Amino Acids. 2009 Nov 28. Positron emission tomography imaging of prostate cancer.
92. ^ Braun K, Ehemann V, Wiessler M, Pipkorn R, Didinger B, Mueller G, Waldeck W. Int J Med Sci. 2009 Nov 18;6(6):338-47. High-Resolution Flow Cytometry: a Suitable Tool for Monitoring Aneuploid Prostate Cancer Cells after TMZ and TMZ-BioShuttle Treatment.
93. ^ Peyromaure M, Valéri A, Rebillard X, Beuzeboc P, Richaud P, Soulié M, Salomon L. Prog Urol. 2009 Dec;19(11):803-9. Characteristics of prostate cancer in men less than 50-year-old.
94. ^ Mongiat-Artus P, Peyromaure M, Richaud P, Droz JP, Rainfray M, Jeandel C, Rebillard X, Moreau JL, Davin JL, Salomon L, Soulié M. Prog Urol. 2009 Dec;19(11):810-7. Recommendations for the treatment of prostate cancer in the elderly man: A study by the oncology committee of the French association of urology.
95. ^ Picard JC, Golshayan AR, Marshall DT, Opfermann KJ, Keane TE. Urol Oncol. 2009 Nov 26. The multi-disciplinary management of high-risk prostate cancer.
96. ^ Mouraviev V, Evans B, Polascik TJ (2006). "Salvage prostate cryoablation after primary interstitial brachytherapy failure: a feasible approach". Prostate Cancer Prostatic Dis. 9 (1): 99–101. doi:10.1038/sj.pcan.4500853. PMID 16314889. 
97. ^ "Prostate Cancer At A Glance". ShaveMagazine.com. http://www.shavemagazine.com/body/health/090401/2. 
98. ^ Fan JK, Wei N, Ding M, Gu JF, Liu XR, Li BH, Qi R, Huang WD, Li YH, Xiong XQ, Wang J, Li RS, Liu XY. Int J Cancer. 2009 Nov 30. Targeting gene-virotherapy for Prostate cancer by DD3-driven oncolytic virus harboring IL-24 gene.
99. ^ http://yedda.com/questions/Low_fat_milk_causes_prostate_cancer_7351021963170/
100. ^ ACS :: What Are The Risk Factors for Prostate Cancer?
101. ^ Jemal, A; Murray T; Ward E; Samuels A; Tiwari RC; Ghafoor A; Feuer EJ; Thun MJ (Jan-February 2005). "Cancer statistics, 2005". CA Cancer J Clin 55 (1): 10–30. doi:10.3322/canjclin.55.1.10. PMID 15661684.  Erratum in: CA Cancer J Clin. 2005 Jul-Aug;55(4):259.
102. ^ Wakai, K (February 2005). "Descriptive epidemiology of prostate cancer in Japan and Western countries". Nippon Rinsho 63 (2): 207–12. PMID 15714967.  Review. (Japanese)
103. ^ Yeole, BB; Sunny L (Jun-December 2001). "Population based survival from prostate cancer in Mumbai (Bombay), India". Indian J Cancer 38 (2–4): 126–32. PMID 1259345. 
104. ^ Hsing, AW; Tsao L, Devesa SS (January 1 2000). "International trends and patterns of prostate cancer incidence and mortality". Int J Cancer 85 (1): 60–7. doi:10.1002/(SICI)1097-0215(20000101)85:1<60::AID-IJC11>3.0.CO;2-B. PMID 10585584. 
105. ^ Osegbe, DN (April 1997). "Prostate cancer in Nigerians: facts and nonfacts". J Urol 157 (4): 1340–3. doi:10.1016/S0022-5347(01)64966-8. PMID 9120935. 
106. ^ Di Blasio CJ, Rhee AC, Cho D, Scardino PT, Kattan MW (2003). "Predicting clinical end points: treatment nomograms in prostate cancer". Semin Oncol 30 (5): 567–86. doi:10.1016/S0093-7754(03)00351-8. PMID 14571407. 
107. ^ Huggins C, Steven RE and Hodges CV, Studies on prostatic cancer. Arch. Sug. 43:209–223, 1941.
108. ^ Hellerstedt BA, Pienta KJ (2002). "The current state of hormonal therapy for prostate cancer". CA Cancer J Clin 52 (3): 154–79. doi:10.3322/canjclin.52.3.154. PMID 12018929. 
109. ^ Feldman BJ, Feldman D (October 2001). "The development of androgen-independent prostate cancer". Nat. Rev. Cancer 1 (1): 34–45. doi:10.1038/35094009. PMID 11900250. 
110. ^ Chuu CP, Hiipakka RA, Fukuchi J, Kokontis JM, Liao S (March 2005). "Androgen causes growth suppression and reversion of androgen-independent prostate cancer xenografts to an androgen-stimulated phenotype in athymic mice". Cancer Res. 65 (6): 2082–4. doi:10.1158/0008-5472.CAN-04-3992. PMID 15781616. 
111. ^ Chuu CP, Hiipakka RA, Kokontis JM, Fukuchi J, Chen RY, Liao S (July 2006). "Inhibition of tumor growth and progression of LNCaP prostate cancer cells in athymic mice by androgen and liver X receptor agonist". Cancer Res. 66 (13): 6482–6. doi:10.1158/0008-5472.CAN-06-0632. PMID 16818617. 
112. ^ Gupta S, Hastak K, Ahmad N, Lewin JS, Mukhtar H (August 2001). "Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols". Proc. Natl. Acad. Sci. U.S.A. 98 (18): 10350–5. doi:10.1073/pnas.171326098. PMID 11504910. 
113. ^ Cooperberg MR, Pasta DJ, Elkin EP, et al. (June 2005). "The University of California, San Francisco Cancer of the Prostate Risk Assessment score: a straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy". J. Urol. 173 (6): 1938–42. doi:10.1097/01.ju.0000158155.33890.e7. PMID 15879786. 
114. ^ Cooperberg MR, Freedland SJ, Pasta DJ, et al. (November 2006). "Multiinstitutional validation of the UCSF cancer of the prostate risk assessment for prediction of recurrence after radical prostatectomy". Cancer 107 (10): 2384–91. doi:10.1002/cncr.22262. PMID 17039503. 
115. ^ May M, Knoll N, Siegsmund M, et al. (November 2007). "Validity of the CAPRA score to predict biochemical recurrence-free survival after radical prostatectomy. Results from a european multicenter survey of 1,296 patients". J. Urol. 178 (5): 1957–62; discussion 1962. doi:10.1016/j.juro.2007.07.043. PMID 17868719. 
116. ^ Zhao KH, Hernandez DJ, Han M, Humphreys EB, Mangold LA, Partin AW (August 2008). "External validation of University of California, San Francisco, Cancer of the Prostate Risk Assessment score". Urology 72 (2): 396–400. doi:10.1016/j.urology.2007.11.165. PMID 18372031. 
117. ^ http://www.ncbi.nlm.nih.gov/pubmed/19509351?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1
118. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html. Retrieved Nov. 11, 2009. 
119. ^ Overview: Prostate Cancer—What Causes Prostate Cancer? American Cancer Society (2 May 2006). Retrieved on 5 April 2007
120. ^ Prostate Cancer FAQs. State University of New York School of Medicine Department of Urology (31 August 2006). Retrieved on 5 April 2007
121. ^ Potosky AL, Miller BA, Albertsen PC, Kramer BS (February 1995). "The role of increasing detection in the rising incidence of prostate cancer". JAMA 273 (7): 548–52. doi:10.1001/jama.273.7.548. PMID 7530782. 
122. ^ Lippman SM, Klein EA, Goodman PJ, et al. (January 2009). "Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT)". JAMA 301 (1): 39–51. doi:10.1001/jama.2008.864. PMID 19066370. 
123. ^ Gine Kolata (June 15, 2008). "New Take on a Prostate Drug, and a New Debate". NY Times. http://www.nytimes.com/2008/06/15/health/15prostate.html?ei=5087&em=&en=813eaa4e10f57756&ex=1213675200&adxnnl=1&adxnnlx=1213503418-GD4DbGjYsDxqV/xuGWnE1A. Retrieved 15 June 2008. 
124. ^ Adams J (1853). "The case of scirrhous of the prostate gland with corresponding affliction of the lymphatic glands in the lumbar region and in the pelvis". Lancet 1. ^{[page needed]}
125. ^ Lytton B (June 2001). "Prostate cancer: a brief history and the discovery of hormonal ablation treatment". The Journal of Urology 165 (6 Pt 1): 1859–62. doi:10.1016/S0022-5347(05)66228-3. PMID 11371867. 
126. ^ Young, H. H. Four cases of radical prostatectomy. Johns Hopkins Bull. 16, 315 (1905).
127. ^ Walsh PC, Lepor H, Eggleston JC (1983). "Radical prostatectomy with preservation of sexual function: anatomical and pathological considerations". The Prostate 4 (5): 473–85. doi:10.1002/pros.2990040506. PMID 6889192. 
128. ^ Huggins CB, Hodges CV (1941). "Studies on prostate cancer: 1. The effects of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate". Cancer Res 1. ^{[page needed]}
129. ^ Schally AV, Kastin AJ, Arimura A (November 1971). "Hypothalamic follicle-stimulating hormone (FSH) and luteinizing hormone (LH)-regulating hormone: structure, physiology, and clinical studies". Fertility and Sterility 22 (11): 703–21. PMID 4941683. 
130. ^ Tolis G, Ackman D, Stellos A, et al. (March 1982). "Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists". Proceedings of the National Academy of Sciences of the United States of America 79 (5): 1658–62. doi:10.1073/pnas.79.5.1658. PMID 6461861. 
131. ^ Denmeade SR, Isaacs JT (May 2002). "A history of prostate cancer treatment". Nature Reviews. Cancer 2 (5): 389–96. doi:10.1038/nrc801. PMID 12044015. 
132. ^ Scott WW, Johnson DE, Schmidt JE, et al. (December 1975). "Chemotherapy of advanced prostatic carcinoma with cyclophosphamide or 5-fluorouracil: results of first national randomized study". The Journal of Urology 114 (6): 909–11. PMID 1104900. 
133. ^ Grotendorst GR, Lau LF, Perbal B (June 2000). "CCN proteins are distinct from and should not be considered members of the insulin-like growth factor-binding protein superfamily". Endocrinology 141 (6): 2254–6. doi:10.1210/en.141.6.2254. PMID 10830315. 
134. ^ Samani AA, Yakar S, LeRoith D, Brodt P (February 2007). "The role of the IGF system in cancer growth and metastasis: overview and recent insights". Endocrine Reviews 28 (1): 20–47. doi:10.1210/er.2006-0001. PMID 16931767. 
135. ^ Jenkins PJ, Bustin SA (August 2004). "Evidence for a link between IGF-I and cancer". European Journal of Endocrinology 151 (Suppl 1): S17–22. doi:10.1530/eje.0.151S017. PMID 15339239. 
136. ^ Linja MJ, Savinainen KJ, Saramäki OR, Tammela TL, Vessella RL, Visakorpi T (May 2001). "Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer". Cancer Research 61 (9): 3550–5. PMID 11325816. http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11325816. 
137. ^ Ford OH, Gregory CW, Kim D, Smitherman AB, Mohler JL (November 2003). "Androgen receptor gene amplification and protein expression in recurrent prostate cancer". The Journal of Urology 170 (5): 1817–21. doi:10.1097/01.ju.0000091873.09677.f4. PMID 14532783. 
138. ^ Kokontis J, Takakura K, Hay N, Liao S (March 1994). "Increased androgen receptor activity and altered c-myc expression in prostate cancer cells after long-term androgen deprivation". Cancer Research 54 (6): 1566–73. PMID 7511045. http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=7511045. 
139. ^ Umekita Y, Hiipakka RA, Kokontis JM, Liao S (October 1996). "Human prostate tumor growth in athymic mice: inhibition by androgens and stimulation by finasteride". Proceedings of the National Academy of Sciences of the United States of America 93 (21): 11802–7. doi:10.1073/pnas.93.21.11802. PMID 8876218. 
140. ^ Kokontis JM, Hsu S, Chuu CP, et al. (December 2005). "Role of androgen receptor in the progression of human prostate tumor cells to androgen independence and insensitivity". The Prostate 65 (4): 287–98. doi:10.1002/pros.20285. PMID 16015608. 

External links

• Prostate Cancer at American Cancer Society
• Prostate Cancer From Cancer Management: A Multidisciplinary Approach
• Prostate Cancer & Endothelin: PMAP The Proteolysis Map-animation
• Prostate cancer at the Open Directory Project
• Interactive Health Tutorials Medline Plus: What's Prostate Cancer Using animated graphics and you can also listen to the tutorial
• Highlights of ASCO 2007 Prostate Symposium, Anna Ferrari. Overview for doctors of ongoing European and U.S. clinical studies of prostate cancer presented at the New York Cancer Consortium. Data on screening, and treatment of local, intermediate and advanced prostate cancer by surgery, radiation and hormones. Answering the question, "What do we tell our patients about treatment decisions?"

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