Prostate cancer

Anatomy of prostate gland

Prostate cancer is the most common cancer among American men if skin cancer is excluded. American Cancer Society estimates each year more than 230,900 new cases of prostate cancer are diagnosed in the United State. It is estimated that more than 29,000 men dies of this disease each year. Important risk factors for the development of prostate cancer include increasing age, black race, and family history of prostate. Increased dietary fat, and vasectomy may increase the risk of prostate cancer. Its incidence shows great variation depending up on the geographical location.

Early stages of prostate cancer may be completely without symptoms. Obstruction to urinary flow is the most common symptom of prostate cancer. It may also present with blood in the urine, urinary infections and frequent urination. Advanced disease may present as leg swelling, bone pain, fractures, or paralysis.

Prostate cancer is a disease in which cancer develops in the prostate, a gland important in male reproduction. Cancer occurs when cells that form the basic building blocks of the prostate multiply out of control. These cells may spread (metastasize) from the prostate to other parts of the body, particularly the bones and lymph nodes. Prostate cancer can cause severe pain, weight loss, erectile dysfunction, difficulty urinating and can result in death.

Prostate cancer only occurs in men and develops most frequently in individuals over fifty years old. It is the second most common type of cancer in men and is responsible for more deaths than any cancer except for lung cancer. However, a number of men who develop prostate cancer never have symptoms, undergo no treatment, and die of unrelated illness. A number of things, including diet, have been implicated in the development of prostate cancer but, as of 2005, it is not a preventable disease.

Prostate cancer is most often discovered by screening blood tests (such as PSA) or by physical examination of the prostate gland by a health care provider. Confirmation of prostate cancer is typically accomplished by removing a piece of the prostate (biopsy) and examining it under a microscope. Further tests, such as X-rays and bone scans, may be performed to determine whether prostate cancer has spread.

Prostate cancer can be treated with surgery, hormone treatment, radiation treatment, occasionally chemotherapy, or a combination thereof. The age and underlying health of the individual, as well as the extent of spread, appearance under the microscope, and response of the cancer to initial therapy are important in determining the outcome of the disease. Since prostate cancer is a disease of older men, a number of men will die of other causes before the prostate cancer can spread or cause symptoms; this makes selecting therapy options difficult.

The prostate

The prostate is a male reproductive organ which helps make and store semen. In adult men, a typical prostate is about three centimeters long and weighs about twenty grams.

Symptoms

Early prostate cancer commonly causes no symptoms. Often it is diagnosed during the workup for an elevated PSA noticed during a routine check-up. Sometimes, however, prostate cancer does cause symptoms, often similar to those of diseases such as non-malignant 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 may also cause problems with sexual function, such as difficulty achieving erection or painful ejaculation.

Pathophysiology

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

Prostate cancer begins when normal semen-secreting prostate gland cells mutate into cancer cells. Prostate cancer, therefore, is an adenocarcinoma, or glandular cancer. Initially small clumps of cancer cells remain confined to otherwise normal prostate glands, a condition known as carcinoma in situ or prostatic intraepithelial neoplasia. 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 cancerous tumor because it is a mass of cells which can invade other parts of the body. This invasion of other organs is called metastasis. Prostate cancer most usually metastasizes to the lymph nodes, the rectum, the bladder, and the bones.

Epidemiology

A man's risk of developing prostate cancer is related to his age, genetics, race, diet, lifestyle, medications, and other factors. The primary risk factor is age. Prostate cancer is uncommon in men less than 45, but becomes more common with advancing age. The average age at the time of diagnosis is 70.

A genetic predisposition to prostate cancer is suggested by an increased incidence among certain racial groups, in identical twins of men with prostate cancer, and in men with certain genes. In the United States, prostate cancer more usually affects black men than white or Hispanic men, and is also more deadly in black men.

Dietary amounts of certain foods, vitamins, and minerals can contribute to prostate cancer risk. Higher consumption of animal fat and lower intake of fruits and vegetables both increase prostate cancer risk. These effects are probably related to increased intake of alpha-linoleic acid (found in animal fat) at the expense of linoleic acid (found in vegetable oils). Other dietary factors that may increase prostate cancer risk include lower intake of vitamin E (found in green leafy vegetables), lycopene (found in tomatoes), omega-3 fatty acids (found in fatty fishes like salmon), and the mineral selenium. Lower blood levels of vitamin D also may increase the risk of developing prostate cancer. This may be linked to lower exposure to ultraviolet (UV) light, since UV light exposure can increase vitamin D in the body.

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.

Screening

Cancer screening is a test to detect unsuspected cancers in the population. Screening tests suitable for large numbers of healthy people must be relatively affordable, safe, noninvasive procedures with acceptably low rates of false positive results. If signs of cancer are detected, more definitive and invasive followup tests are performed to confirm the diagnosis. Prostate cancer can be screened for by a digital rectal exam (DRE) along with prostate specific antigen (PSA) blood testing.

Screening for prostate cancer is controversial because it is not clear if the benefits of screening outweigh the risks of follow-up diagnostic tests and cancer therapys. When screening for prostate cancer, the PSA test may detect small cancers that would never become life threatening, but once detected will lead to therapy. This situation, called overdiagnosis, puts men at risk for complications from unnecessary therapy such as surgery or radiation. Followup procedures used to diagnose prostate cancer (prostate biopsy) may cause side effects, including bleeding and infection. Prostate cancer therapy may cause incontinence (inability to control urine flow) and erectile dysfunction (erections inadequate for intercourse). For these reasons, it is important that the benefits and risks of diagnostic procedures and therapy be taken into account when considering whether to undertake cancer screening.

Digital rectal examination

Digital rectal examination (DRE) is a procedure during which the clinician inserts a gloved, lubricated finger into the rectum in order to feel the size and shape of the prostate to find areas that are for hard or lumpy, which may indicate cancer. DRE can only detect abnormalities in one area of the prostate (the zone that can be felt through the rectum). Fortunately, this is where most prostate cancers arise.

Prostate specific antigen

A blood test for prostate-specific antigen (PSA) measures the levels of PSA in a blood sample. Under normal circumstances, PSA is not found in the blood, but levels lower than 4 ng/mL (nanograms per milliliter) are considered normal. Levels greater than 10 ng/mL are considered abnormal. PSA levels between 4 and 10 ng/mL are considered to be borderline. PSA tests for prostate cancer are a subject of some controversy among clinicians and researchers. This is because some men who have prostate cancer do not have elevated PSA (andgt;4 ng/mL), while some men with elevated levels do not have prostate cancer. This is far from being a perfect test, but it is the best method currently and used commonly.

Elevated PSA levels can occur for a number of reasons. They may rise in men who have prostate cancer, non-malignant prostate hyperplasia (BPH), or an infection in the prostate (prostatitis). To maximize the accuracy of a PSA test: (1) don't ejaculate for 2 days previous to having a PSA test as this can raise PSA levels, and (2)inform your clinician if you are taking finasteride (marketed as Proscar or Propecia) or dutasteride (marketed as Avodart). These drugs, used to treat BPH and baldness affect the metabolism of testosterone throughout your body and will likely lower your PSA levels. Also, (3) the DRE needs to be performed after drawing blood for the PSA test, as palpation of the prostate can stimulate it to produce PSA and lead to elevated PSA levels in the serum. Some herbal supplements can also affect PSA levels. Discuss any supplements you are taking with your clinician previous to having a PSA test.

The most recent trend is to consider the rate of change of the PSA level as an indication of the risk of cancer. This requires at least two PSA tests be done over a period of time. Abnormal DRE or high serum PSA levels are reasons for a medical follow up. The results of these tests will help to determine whether further tests are necessary to check for cancer.

When the total PSA blood test is in the grey zone (between 4 and 10 ng/mL) and the DRE is normal, the percentage of free PSA (unbound to other proteins) in the blood is used to distinguish between BPH and prostate cancer. A low value for percent-free PSA indicates a higher probability of prostate cancer.

Currently, a biopsy is the only procedure that can definitively diagnose prostate cancer (see below).

Diagnosis

Normal prostate (A) and prostate cancer (B). In prostate cancer, the regular glands of the normal prostate are replaced by irregular glands and clumps of cells, as seen in these pictures taken through a microscope.

If a man has symptoms or test results that suggest prostate cancer, his doctor asks about his personal and family medical history, performs a physical exam, and may order laboratory tests. The exams and tests may include a digital rectal exam, a urine test to check for blood or infection, and a blood test to measure PSA. In some cases, the doctor also may check the level of prostatic acid phosphatase (PAP) in the blood, particularly if the results of the PSA indicate there might be a problem.

The doctor may order exams to learn more about the cause of the symptoms. These may include:

• Transrectal ultrasonography -- sound waves that cannot be heard by humans (ultrasound) are sent out by a probe inserted into the rectum. The waves bounce off the prostate, and a computer uses the echoes to create a picture called a sonogram.
• Intravenous pyelogram -- a series of x-rays of the organs of the urinary tract.
• Cystoscopy -- a procedure in which a doctor looks into the urethra and bladder through a thin, lighted tube.

If test results suggest that cancer may be present, the man will need to have a biopsy. During a biopsy, the doctor removes tissue samples from the prostate, commonly with a needle. A biopsy gun inserts and removes hollow core needles (commonly three to six for each side of the prostate) in less than a second. The needles are very fine and remove only small cores of tissue. In this way, small 'samples' of the prostate are removed. The tissue samples are then examined under a microscope to determine if cancer cells are present and to evaluate the extent of the cancer. Some men have reported that this is the most physically uncomfortable part of their experience of being diagnosed with prostate cancer.

Gleason grading

A pathologist looks at the tissue under a microscope to check for cancer cells. If cancer is present, the pathologist commonly 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 most common method of grading prostate cancer, called the Gleason system, uses scores of 2 to 10, with 10 indicating the most aberrant growing and 'malignant' samples. The pathologist assigns a number between 1 and 5 to the most common pattern observed under the microscope. The second most common pattern is also assigned a number. The sum of these numbers makes up the Gleason score. Another system uses G1 through G4. It is important that the pathologist grading the tumor have a lot of experience looking at prostate tumors, as the grade of the tumor is one of the major factors in determining the therapy recommendation. This is because tumors with higher scores or grades are more likely to grow and spread than tumors with lower scores.

Stages

An important part of the evaluation of prostate cancer is determination of the stage, or how far the cancer has spread. The most common system is the TNM system, which evaluates the size of the tumor, the number of involved lymph nodes, and any other metastasis. The microscopic appearance of the prostate, quantified as the Gleason score, is also incorporated into the staging system. As with a number of other cancers, these are often grouped into four stages (I-IV). The Whitmore-Jewett stage is another method sometimes used. The purpose of staging is to help determine prognosis and to assist in selecting therapies; a good staging system will have similar characteristics for most cancers at a given stage.

Treatment

Treatment for prostate cancer depends on the stage of the disease and the grade of the tumor (which indicates how abnormal the cells look, and how likely they are to grow or spread). Other important factors in planning therapy are the man's age and general health and his feelings about the therapys and their possible side effects.

Treatment for prostate cancer may involve watchful waiting, surgery, radiation treatment, or hormonal treatment. Some patients receive a combination of therapies. The patient and his doctor may want to consider both the benefits and possible side effects of each option, particularly the effects on sexual activity and urinary control, and other concerns about quality of life.

It is hard to limit the effects of therapy so that only cancer cells are removed or destroyed. Because healthy cells and tissues may be damaged, therapy often causes unwanted side effects. The side effects of cancer therapy depend mainly on the type and extent of the therapy. Also, each patient reacts differently.

During and after therapy, the doctor will continue to follow the patient. The doctor will examine the man regularly to be sure that the disease has not returned or progressed, and will decide what other medical care may be needed. Follow-up exams may include x-rays, scans, and lab tests, such as the PSA blood test.

Watchful waiting

Watchful waiting is the active observation and regular monitoring of a patient without actual therapy. This includes frequent PSA monitoring. Treatment will be started only if symptoms occur or worsen or if the rate of PSA rise is concerning. Watchful waiting may be suggested when prostate cancer is found at an early stage and appears to be slow growing. Also, watchful waiting may be advised for older men or men with other serious medical problems. For these men, the risks and possible side effects of surgery, radiation treatment, or hormonal treatment may outweigh the possible benefits.

Eventhough men who choose watchful waiting avoid the side effects of surgery and radiation, there can be some negative aspects to this choice. Watchful waiting may reduce the chance of controlling the disease before it spreads. Also for older men it may be harder to manage surgery and radiation treatment as they age.

Surgery

Surgery is a common therapy for early stage prostate cancer. The doctor may remove all of the prostate (radical prostatectomy) or only part of it. In some cases, the doctor can use a new technique known as nerve-sparing surgery. This type of surgery may save the nerves that control erection. However, men with large tumors or tumors that are very close to the nerves may not be able to have this surgery.

• In radical retropubic prostatectomy, the doctor removes the entire prostate and nearby lymph nodes through an incision in the abdomen.
• In radical perineal prostatectomy, the doctor removes the entire prostate through an incision between the scrotum and the anus. Nearby lymph nodes are sometimes removed through a separate incision in the abdomen.

Surgical removal of the prostate and surrounding tissue (radical prostatectomy) has long been recognized as one of the most effective forms of treatment for prostate cancer. A conventional radical prostatectomy involves an open incision across the abdomen. Robotic laparoscopic prostatectomy represents a major advance in the therapy of prostate cancer by offering men a less-invasive alternative to traditional surgery. The surgeon performs the same nerve-sparing procedure done in conventional laparoscopic prostatectomy, but with greater precision. The prostate, nearby lymph nodes, seminal vesicles and adjacent tissue are removed through the small incisions, which are closed with a few stitches.

• In transurethral resection of the prostate (TURP), the doctor removes part of the prostate with an instrument that is inserted through the urethra. The cancer is cut from the prostate by electricity passing through a small wire loop on the end of the instrument. This method is used mainly to remove tissue that blocks urine flow.

If the pathologist finds cancer cells in the lymph nodes, it is likely that the disease has spread to other parts of the body. Sometimes, lymph nodes are removed before doing a prostatectomy. If the prostate cancer has not spread to the lymph nodes, the doctor then removes the prostate. But if cancer has spread to the nodes, the doctor commonly does not remove the prostate, but may suggest other therapy.

While the above was the standard of care through the 1980s and early part of 1990s recent Journal publications indicate that "Radical prostatectomy combined with early adjunctive hormonal treatment for patients with nodal metastasis is superior to all other forms of treatment and should be considered the standard of care. This approach provides survival rates comparable with patients with clinically organ-confined prostate cancer."

Patients are often uncomfortable for the first few days after surgery. Pain commonly can be controlled with medication. The patient will wear a catheter (a tube inserted into the urethra) to drain urine for 10 days to 3 weeks. It is also common for patients to feel extremely tired or weak for a while. The length of time it takes to recover from an operation varies.

Surgery to remove the prostate can cause long-term problems, including impotence and/or fecal or urinary incontinence. Nerve-sparing surgery is an attempt to avoid the problem of impotence. When the doctor can use nerve-sparing surgery and the operation is fully successful, impotence may be only temporary or partial. Still, some men who have this procedure may be permanently impotent. Different men experience these side effects to be a greater or lesser problem. Men who have a prostatectomy no longer produce semen, so they have dry orgasms. Men who wish to father children may consider sperm banking or a sperm retrieval procedure before surgery.

Radiation treatment

Radiation treatment - Radiation can be delivered to the prostate through external machines or by little andquot;seedsandquot;, such as those shown above. These seeds are implanted into the prostate and deliver radiation directly to the gland.

Radiation treatment (also called radiotherapy) uses high-energy x-rays to kill cancer cells. Like surgery, radiation treatment is local treatment; it can affect cancer cells only in the treated area. In early stage prostate cancer, radiation can be used instead of surgery, or it may be used after surgery to destroy any cancer cells that may remain in the area. In advanced stages, it may be given to relieve pain or other problems.

Radiation may be directed at the body by a linear accelerator, or it may come from tiny radioactive seeds placed inside or near the tumor (internal or implant radiation, or brachytherapy). Men who receive radioactive seeds alone commonly have small tumors. Some men with prostate cancer receive both kinds of radiation treatment. For external radiation treatment, patients go to the hospital or clinic, commonly 5 days a week for several weeks. Patients may stay in the hospital for a short time for implant radiation.

Radiation treatment may cause patients to become extremely tired, particularly in the later weeks of therapy. Resting is important, but doctors commonly encourage men to try to stay as active as they can. Some men may have diarrhea or frequent and uncomfortable urination. When men with prostate cancer receive external radiation treatment, it is uncommon for the skin in the treated area to become red, dry, or tender, however there may be hair loss in the treated area. The loss is commonly temporary. Both types of radiation treatment may cause impotence in some men. While internal radiation treatment may cause temporary urinary incontinence, external radiation treatment causes temporary bowel inflammation. Long-term side effects from internal radiation treatment are uncommon.

External beam radiotherapy with curative intent for localised prostate cancer is frequently given with concurrent hormone ablation treatment. The indications for adding hormone treatment are currently (September 2005) in a state of flux, as is the recommended interval for such therapy. Generally, patients who are thought to have a significant (andgt;15%) risk of lymph node involvement or spread beyond the prostate are given concurrent hormone ablation drugs. Oncologists give such therapy anywhere from 2 months to 3 years in overall duration.

External beam radiotherapy, prostate implant brachytherapy, and radical surgery all appear equally efficacious in curing localised prostate cancer.

Cryotherapy

Cryotherapy is another method of treating prostate cancer. Cryotherapy is the insertion of metal rods into the prostate and circulating liquid nitrogen through these rods. This process lowers the temperature to about minus 374° F. As the tissue freezes, the formation and expansion of ice crystals within the malignant cells cause them to rupture and die. A catheter is placed inside the urethra and a warming solution is circulated to prevent damage to the urethra. Short term results have been good however long term results appear to suggest that it is not as effective as surgery or radiation. Additionally, impotence results from cryotherapy 90 percent of the time.

Hormonal treatment

Hormonal treatment keeps cancer cells from getting the male hormones they need to grow. It is called systemic treatment because it can affect cancer cells throughout the body. Systemic treatment is used to treat cancer that has spread. Sometimes this type of treatment is used to try to prevent the cancer from coming back after surgery or radiation therapy.

There are several forms of hormonal treatment:

• Orchiectomy is surgery to remove the testicles, which are the main source of male hormones.
• Drugs known as luteinizing hormone-releasing hormone (LHRH) agonists can prevent the testicles from producing testosterone. Examples are leuprolide, goserelin, and buserelin.
• Drugs known as antiandrogens can block the action of androgens. Two examples are flutamide and bicalutamide.
• Drugs that can prevent the adrenal glands from making androgens include ketoconazole and aminoglutethimide. These drugs are rarely used for this purpose.

After orchiectomy or therapy with an LHRH agonist, the body no longer gets testosterone from the testicles. However, the adrenal glands still produce small amounts of male hormones. Sometimes, the patient is also given an antiandrogen, which blocks the effect of any remaining male hormones. This combination of therapys is known as total androgen blockade (TAB), combined hormonal treatment (CHT), combined androgen blockade (CAB), or maximal androgen deprivation (MAD). Doctors do not know for sure whether total androgen blockade is more effective than orchiectomy or LH-RH agonist alone.

Prostate cancer that has spread to other parts of the body commonly can be controlled with hormonal treatment for a period of time, often several years. Eventually, however, most prostate cancers are able to grow with very little or no male hormones. When this happens, hormonal treatment is no longer effective, and the doctor may suggest other forms of therapy that are under study.

The side effects of hormonal treatment depend largely on the type of therapy. Orchiectomy and LH-RH agonists often cause side effects such as impotence, hot flashes and loss of sexual desire. When first taken, an LH-RH agonist may make a patient's symptoms worse for a short time. This temporary problem is called "flare." Gradually, however, the therapy causes a man's testosterone level to fall. Without testosterone, tumor growth slows down and the patient's condition improves. (To prevent flare, the doctor may give the man an antiandrogen for a while along with the LH-RH agonist.) In some cases, men may be prescribed intermittent courses of hormone treatment, with careful monitoring by their doctor to determine when to begin the next course of therapy.

Antiandrogens can cause nausea, vomiting, diarrhea, or breast growth or tenderness. If used a long time, ketoconazole may cause liver problems, and aminoglutethimide can cause skin rashes. Men who receive total androgen blockade may experience more side effects than men who receive a single method of hormonal treatment. Any method of hormonal treatment that lowers androgen levels can contribute to weakening of the bones in older men.

Prognosis

Prostate cancer affects eighteen percent of American men but is the cause of death in only three percent.

Prevention

In addition to modifying known risk factors for prostate cancer (such as decreasing intake of animal fat

The two selective estrogen receptor modulator drugs acapodene

History

Eventhough the prostate was first described by Niccolo Massa in 1536 and illustrated by Andreas Vesalius in 1538, prostate cancer was not identified until 1853.

In 1941, Charles B. Huggins published studies which 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.

Radiation treatment 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.

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External links

• Prostate Cancer Blog from Medicineworld