Prostate cancer develops from cells of the prostate gland. Eventually the cancer cells may spread outside the gland to other parts of the body. Most prostate cancers grow very slowly. Autopsy studies show that many elderly men who died of other diseases also had a prostate cancer that neither they nor their doctor were aware of. But some prostate cancers can grow and spread quickly.
The prostate gland is about the size of a walnut and is located in front of the rectum, behind the base of the penis, and under the bladder. It is found only in men, and contains gland cells that produce some of the seminal fluid, which protects and nourishes sperm cells.
The prostate surrounds the upper part of the urethra, the tube that carries urine and semen out of the penis. Nerves located next to the prostate take part in causing an erection of the penis, and treatments that remove or damage these nerves can cause erectile dysfunction, also known as impotence.
Lymph is a clear fluid that contains tissue waste products and immune system cells. Lymphatic vessels carry this fluid to lymph nodes (small, bean-shaped collections of immune system cells important in fighting infections). Most lymphatic vessels of the prostate lead to pelvic lymph nodes. Cancer cells can enter lymph vessels and spread out along these vessels to reach lymph nodes, where they can continue to grow. If prostate cancer cells have multiplied in the pelvic lymph nodes, they are more likely to have spread to other organs of the body as well.
Although several other cell types are found in the prostate, over 99% of prostate cancers develop from glandular cells. The medical term for a cancer that starts in glandular cells is adenocarcinoma. Because other types of prostate cancer are so rare, when someone speaks of prostate cancer it is assumed they are referring to a prostatic adenocarcinoma, unless they specifically mention some other cell type.
Prostatic intraepithelial neoplasia (PIN) is a condition in which there are changes in the microscopic appearance (the size, shape, or the rate at which they multiply) of prostate epithelial cells. Older men are more likely to have this condition. PIN is classified as either low grade or high grade. If a person has high grade PIN, repeat biopsies and PSA tests should be done regularly. PIN may lead to the development of prostate cancer. At this time there is no standard treatment for PIN. Studies are being done to determine if treatments used for BPH (benign prostatic hyperplasia) are also effective in treating PIN.
Prostate cancer is the most common cancer, excluding nonmelanoma skin cancers, in American men. The American Cancer Society estimates during 2001 approximately 198,100 new cases of prostate cancer will be diagnosed in the United States.
Prostate cancer is the second leading cause of cancer death in men, exceeded only by lung cancer. The American Cancer Society estimates that 31,500 men in the United States will die of this disease during 2001. Prostate cancer accounts for about 11% of male cancer-related deaths.
Ninety two percent of men diagnosed with prostate cancer survive at least 5 years, and 67% survive at least 10 years. Fifty-eight percentof all prostate cancers are found while they are still localized (that is, confined to the prostate), and the 5-year relative survival rate for men with localized prostate cancer is 100%. Thirty-one percent of prostate cancers have already spread locally (to tissues near the prostate) at the time of diagnosis. The 5-year survival rate for these men is 94%. Among the 11% of men whose prostate cancers have already spread to distant parts of the body at the time of diagnosis, about 31% are expected to survive at least five years.
A risk factor is anything that increases a person's chance of developing a disease such as cancer. Different cancers have different risk factors. Many people with one or more risk factors never develop cancer, while others with this disease have no known risk factors. It is important, however, to know about risk factors so that appropriate action can be taken such as changing a health behavior, or being monitored closely for a potential cancer.
While the causes of prostate cancer are not yet completely understood, researchers have found several factors that are consistently associated with an increased risk of developing this disease.
Age: The chance of having prostate cancer increases rapidly after age 50. More than 80% of all prostate cancers are diagnosed in men over the age of 65. Race: Prostate cancer is about twice as common among African-American men as it is among white American men. Nationality: Prostate cancer is most common in North America and northwestern Europe. It is less common in Asia, Africa, Central America, and South America. Diet: Results of most studies suggest that men who eat a lot of fat in their diet have a greater chance of developing prostate cancer. Other research indicates that men with a high-fat diet tend to eat fewer fruits and vegetables and more dairy products, and that these factors may be responsible for increasing risk rather than the amount of fat itself. Recent research also suggests that a diet high in calcium and low in fructose (fruit sugar) increases prostate cancer risk. Lycopenes, which are found in especially high levels in some fruits and vegetables (such as cooked or raw tomatoes, grapefruit, and watermelon) also seem to lower prostate cancer risk, as does the mineral selenium. Physical activity: Regular physical activity and maintaining a healthy weight may help reduce prostate cancer risk. Family history: Prostate cancer seems to run in some families, suggesting an inherited or genetic factor. Having a father or brother with prostate cancer doubles a man's risk of developing this disease. The risk is even higher for men with several affected relatives, particularly if their relatives were young at the time of diagnosis. Vasectomy: Some studies have suggested that men who have had a vasectomy (surgery to make men infertile) may have a slightly increased risk for prostate cancer, but this link has not been consistently found. Among the studies that noticed an increase in risk, some found that this risk is highest in men who were younger than 35 when they had a vasectomy. Research to resolve this issue is still in progress. However, most recent studies have not found any increased risk among men who have had this operation.
Because the exact cause of prostate cancer is not known, we do not know if it is possible to prevent most cases of the disease. Many risk factors such as a man's age, race, and family history are beyond his control. But current information on prostate cancer risk factors suggests that some cases might be prevented. One possible risk factor that can be changed is diet. A diet low in fat and consisting mostly of vegetables, fruits, and grains is associated with reduced risk of prostate cancer. The American Cancer Society recommends limiting your intake of high-fat foods from animal sources and choosing most of the foods you eat from plant sources. Eat five or more servings of fruits and vegetables each day. Bread, cereals, grain products, rice, pasta, and beans are also recommended.
There is evidence that development of prostate cancer is linked to increased levels of certain hormones. High levels of androgens (male hormones) may contribute to prostate cancer risk in some men.
Some people with certain types of cancer have DNA mutations they inherited from a parent. Researchers have recently found that inherited DNA changes in certain genes make these people more likely to develop prostate cancer. These genetic changes appear to be responsible for about 10% of prostate cancers.
The Prostate-Specific Antigen Blood Test (PSA) is a test to measure the level of protein that is made by prostate cells. The higher the PSA level, the more likely the presence of prostate cancer. The American Cancer Society recommends PSA should be offered annually by health care providers to men 50 and older with a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. At this time, the health care provider should also discuss the risks and benefits of early detection and treatment of prostate cancer. It is important to understand how the PSA blood test is used in early detection of prostate cancer. PSA levels estimate how likely a man is to have prostate cancer but the test does not provide a definite answer.
Although the PSA blood test is not perfect, it is the best test currently available for early detection of prostate cancer. Since doctors started using this test, the number of prostate cancers found at an early, curable stage has increased. And since most men have normal test results, they can be reassured that they are unlikely to have prostate cancer, especially if their digital rectal exam (DRE) result is also negative.
Although the PSA test is used mainly for early detection, it has value in other situations. In men known to have prostate cancer (based on their biopsy result), the PSA test can help predict prognosis (outlook). Men with very high PSA results are more likely to have cancer that has spread beyond the prostate and are less likely to be cured or have long survival. PSA levels can be used together with clinical examination results and tumor grade to help decide which tests are needed for further evaluation. After surgery or radiation treatment, rising PSA levels can provide an early sign that the cancer is coming back.
The American Cancer Society recommends that health care providers offer men who are 50 or older (as well as younger men with high prostate cancer risk) the opportunity to have a procedure called the digital rectal exam (DRE) as part of their annual physical check-up.
During this examination, a doctor inserts a gloved, lubricated finger into the patient's rectum to feel for any irregular or abnormally firm area that might be a sign of cancer. The prostate gland is located next to the rectum, and most cancers begin in the part of the gland that can be reached by a rectal exam. While it is uncomfortable, the exam causes no pain and only takes a short time.
Digital rectal examination of the prostate should be performed by health care professionals skilled in recognizing subtle prostate abnormalities such as those of symmetry and consistency, as well as the more classic findings of nodules or hard areas. DRE is less effective than the PSA blood test in finding prostate cancer but can sometimes find cancers in men with normal PSA levels. For this reason, the American Cancer Society guidelines recommend use of both the DRE and PSA blood test for men who choose to undergo testing for early prostate cancer detection. The DRE is also used once a man is known to have prostate cancer, in order to help predict whether the cancer has spread beyond his prostate gland, and to detect cancer that has come back after treatment.
TRUS is useful when the PSA or DRE indicates an abnormality, to guide the biopsy needle into exactly the right area of the prostate. But TRUS is not recommended as a routine test for early detection of prostate cancer.
Transrectal ultrasound (TRUS) uses sound waves to create an image of the prostate on a video screen. Sound waves are released from a small probe placed in the rectum. The sound waves create echoes as they enter the prostate. The same rectal probe detects the echoes that bounce back from the prostate and a computer translates the pattern of echoes into a picture. Because prostate tumors and normal prostate tissue often reflect sound waves differently, this test may be useful in detecting tumors, even those which might be too small or located in areas of the gland that cannot be felt by DRE.
Placing the TRUS probe into the rectum may be temporarily uncomfortable, but the procedure itself is essentially painless. The TRUS examination is done in a doctor's office or outpatient clinic. It usually takes about 10-20 minutes.
A biopsy is a surgical procedure in which a sample of tissue is removed for examination under a microscope. A core needle biopsy is the main method used to diagnose prostate cancer. Under transrectal ultrasound guidance a doctor inserts a narrow needle through the wall of the rectum into the area of the prostate gland that appears abnormal or suspicious. The needle then removes a cylinder of tissue, usually about 1/2 inch long and 1/16 inch across, which is sent to the laboratory to see if cancer is present.
The procedure is usually done in the doctor's office and takes about half an hour. Though the procedure sounds painful, it typically causes little discomfort because a special instrument called a biopsy gun inserts and removes the needle in a fraction of a second. Several biopsy samples are often taken from different areas of the prostate. Usually six samples are taken (upper, mid, and lower areas of the left and right sides) to get a representative sample of the gland and tell how much of the gland is affected by the cancer. In some cases, as many as eighteen samples may be taken.
If cancer is found in a prostate biopsy specimen, it will be graded in order to estimate how aggressive it is likely to be (that is how fast it is likely to grow and spread). Grading is done by the pathologist examining the tissue sample taken during the prostate biopsy. Prostate cancers are graded according to how closely they look like normal prostate tissue when viewed under a microscope. The most commonly used prostate cancer grading system is called the Gleason system.
This system assigns a Gleason grade ranging from 1 through 5 based on how much the arrangement of the cancer cells mimics the way normal prostate cells form glands. If the cancer cell clusters resemble the small, regular, evenly spaced glands of normal prostate tissue, a grade of 1 is assigned. If the cancer lacks these features and its cells seem to spread haphazardly through the prostate, it is a grade 5 tumor. Grades 2 through 4 have intermediate features.
Cancers with a high Gleason score are more likely to have already spread beyond the prostate gland at the time they are found. For this reason, the Gleason score (considered together with the blood PSA level and DRE findings) is useful in considering treatment options and selecting additional tests to be done before choosing a treatment.
T stages: There are actually two types of T classifications for prostate cancer. The clinical stage is based on digital rectal exam, needle biopsy, and transrectal ultrasound findings. The pathologic stage is based on surgical removal and examination of the entire prostate gland, both seminal vesicles (two small sacs next to the prostate that store semen) and, in some cases, nearby lymph nodes.T1 refers to a tumor that can't be felt during a digital rectal exam, but cancer cells are found in a biopsy specimen.
T2 means that a doctor can feel the prostate cancer by digital rectal exam (DRE) and that the cancer remains within the prostate gland.
T3 cancers have spread to the connective tissue next to the prostate and/or to the seminal vesicles, but do not involve any other organs.
T4 means that the cancer has spread to tissues next to the prostate (other than the seminal vesicles), such as the bladder's external sphincter (muscles that help control urination), the rectum, and/or the wall of the pelvis.
N stages: N0 means that the cancer has not spread to any lymph nodes. N1 indicates spread to one or more regional (nearby) lymph nodes in the pelvis.
M stages: M0 means that the cancer has not metastasized beyond the regional nodes. M1 means metastases are present in distant (outside of the pelvis) lymph nodes, in bones, or other distant organs such as lungs, liver or brain.
Examinations and Visualizations |
|
|---|---|
Digital rectal examination (DRE) |
A procedure in which a physician inserts a gloved, lubricated finger into the rectum to feel the prostate. |
Chest X-ray |
An image that can show whether cancer has spread to the lungs or other structures such as the ribs. |
Bone scan |
A picture that can show whether cancer has spread to the bone. |
Transrectal ultrasonography (TRUS) |
A procedure in which an instrument is inserted into the rectum and produces sound waves directed at the prostate; from these sound waves, a picture is created. |
Computed tomography (CT) |
A picture produced by a computer from x-rays, showing the prostate and other nearby parts of the body. |
Intravenous pyelogram (IVP) |
An x-ray of the kidneys, ureters, and bladder that is taken after the patient has been injected with a special dye. |
Magnetic resonance imaging (MRI) |
A picture produced by a computer and a high-powered magnet that shows the prostate and other nearby parts of the body. |
Blood Tests |
|
|---|---|
Prostate-specific antigen (PSA) |
A test useful both in diagnosis and follow-up of prostate cancer that detects a blood substance that often increases in cases of prostate cancer and other prostate diseases. |
% free-PSA ratio |
A newer type of PSA test that measures how much PSA is unbound and how much is bound to other proteins in the blood; a low %-free PSA ratio combined with a borderline PSA can help confirm a diagnosis of prostate cancer. |
Tissue Samples |
|
|---|---|
Prostate biopsy |
The removal and microscopic examination of a small sample of the prostate to determine whether it contains cancer cells. |
Pelvic node dissection (also called lymphadenectomy) |
A procedure used to help determine whether prostate cancer has spread--typically done during surgery to remove the prostate. |
The two most common prostate operations are radical prostatectomy and transurethral resection of the prostate (TURP).
In this operation the entire prostate gland plus some tissue around it is removed. Radical prostatectomy is used most often if the cancer is thought not to have spread outside of the gland. The patient is either under general anesthesia (asleep and totally unconscious) or under spinal or epidural anesthesia (the same type of anesthesia often given to women during childbirth to numb the lower half of the body) with sedation during the surgery.
There are two main types of radical prostatectomy – radical retropubic prostatectomy and radical perineal prostatectomy. In the retropubic operation, the surgeon makes a skin incision in the lower abdomen. The surgeon can remove lymph nodes during this operation through the same incision. A nerve-sparing radical retropubic prostatectomy is a modification of this operation. During this procedure, the surgeon carefully feels the small bundles of nerves on either side of the prostate gland. If it appears that the cancer has not spread to these nerves, the surgeon will not remove them. Because these are the nerves that are needed for erections, leaving them intact lowers (but does not eliminate) the risk of impotence (not being able to have an erection) following surgery.
The radical perineal prostatectomy removes the prostate through an incision in the skin between the scrotum and anus. Nerve-sparing operations are more difficult to perform by this approach and lymph nodes cannot be removed through this incision. If lymph node examination is needed for men having this operation, the surgeon can remove some lymph nodes through a very small skin incision in the abdomen by using a laparoscope (a narrow lighted tube).
These operations last from 1 1⁄2 to 4 hours, with the perineal approach taking less time than the retropubic approach. Surgery is followed by an average hospital stay of three days and average time away from work of three to five weeks.
In this operation the surgeon removes part of the prostate gland that surrounds the urethra (the tube through which urine exits the bladder). TURP is most often used to treat men with noncancerous enlargement of the prostate called benign prostatic hyperplasia or BPH. The procedure is also used for men with prostate cancer who cannot have a radical prostatectomy because of advanced age or a serious illness (in addition to their prostate cancer).
TURP can be used to relieve symptoms caused by a cancer before other treatments begin. But it is not expected to cure this disease or remove all of the cancer. Cutting through the skin is not done with this surgery. A tool with a small loop of wire on the end is placed inside the prostate through the urethra. Electricity is passed through the wire to heat it and cut the tissue. Either spinal anesthesia or general anesthesia is used.
Cryosurgery (also called cryotherapy or cryoablation) is used to treat localized prostate cancer by freezing its cells with a metal probe. Warm saline (saltwater) is circulated through a catheter in the urethra to keep it from freezing. The probe is placed through a skin incision located between the anus and scrotum, and guided into the cancer using transrectal ultrasound.
The appearance of prostate tissue in ultrasound images changes when it is frozen. In order to be sure enough prostate tissue is destroyed without too much damage to nearby tissues, the surgeon carefully watches these images during the procedure. Spinal, epidural, or general anesthesia is used during the procedure.
Radiation therapy uses high-energy rays (such as gamma rays or x-rays) and particles (such as electrons, protons, or neutrons) to kill cancer cells. Radiation is sometimes used to treat cancer that is still confined within the prostate gland, or has spread to nearby tissue. If the disease is more advanced, radiation may be used to reduce the size of the tumor and to provide relief from present and future symptoms. Radiation usually eliminates the need for surgery. Patients who do not have a good response with radiation therapy may still have surgery ("salvage prostatectomy") at a later date. Two main types of radiation therapy are used – external beam radiation and brachytherapy. There are several forms of these two main types.
External beam radiation is focused from a source outside the body on the area affected by the cancer. It is much like getting a diagnostic x-ray, but for a longer time. Before treatments start, imaging studies such as CT scans and plain x-rays of the pelvis are done to find the location of the cancer in your body. The radiation team will then make some ink marks on your skin that they will use later as a guide for focusing the radiation in the right area. Patients are usually treated five days per week in an outpatient center over a period of seven or eight weeks, with each treatment lasting a few minutes. The procedure itself is painless.
Internal radiation therapy or brachytherapy uses small radioactive pellets (each about the size of a grain of rice) that are directly implanted (permanently or temporarily) into the prostate. Imaging tests such as transrectal ultrasound, CT scans, or MRI are used to accurately guide placement of the radioactive material.
The radioactive materials (isotopes such as iodine 125 or palladium 103) are placed inside thin needles, which are inserted through the skin of the perineum (area between the scrotum and anus) into the prostate. The permanent pellets, which are sometimes called seeds, give off radiation for weeks or months. Because they are so small, their presence causes little discomfort and they are simply left in place after their radioactive material is used up. Alternatively, needles containing more radioactive material can be placed for less than a day. This approach is called high dose rate brachytherapy. For about a week following insertion of the needles, patients may have some pain in the perineal area and may have red-brown discoloration of their urine.
Strontium 89 (Metastron) is a radioactive substance that is used for treatment of bone pain caused by metastatic prostate cancer. It is injected into a vein and is attracted to areas of bone containing cancer. The radiation given off by the Strontium 89 kills the cancer cells, and relieves the pain caused by bone metastases. About 80% of prostate cancer patients with painful bone metastases are helped by this treatment. If prostate cancer has spread to many bones, this approach is much better than trying to aim external beam radiation at each affected bone. In some cases, Strontium 89 is used together with external beam radiation aimed at the most painful bone metastases.
This treatment is often used in patients for whom other treatments, such as surgery or radiation, may not be good options. This might include older patients or those in poor general health, as well as patients whose prostate cancer has spread beyond the prostate or has come back after treatment. Most evidence shows that hormone therapy works better if it is started as early as possible after the cancer has reached an advanced stage. The goal of hormone therapy is to lower levels of the male hormones, androgens. The main androgen is called testosterone. Androgens are produced mainly in the testicles and cause prostate cancer cells to grow. Lowering androgen levels can make prostate cancers shrink or grow more slowly. But hormone therapy does not cure the cancer. There are several methods used for hormone therapy.
This operation removes the testicles. Although it is a surgical treatment, orchiectomy is considered a hormonal therapy because it works by removing the main source of male hormones. Orchiectomy lowers androgen levels and can temporarily prevent or reduce growth of most prostate cancers.
These drugs decrease the amount of testosterone produced by a man's testicles. LHRH analogs (also called LHRH agonists) are injected either monthly or every three months at the doctor's office or at the oncology center. These drugs can lower the level of testosterone as effectively as surgical removal of the testicles. The two LHRH analogs currently available in the United States are leuprolide (Lupron), and goserelin (Zoladex).
Even after orchiectomy or during treatment with LHRH analogs, a small amount of androgen is still produced by the adrenal glands. Anti-androgens block the body's ability to use androgens. Drugs of this type, such as flutamide (Eulexin) and bicalutamide (Casodex) and nilutamide (Nilandron), are taken as pills, once or three times a day. Anti-androgens are often used in combination with orchiectomy or LHRH analogs. This combination is called total androgen blockade.
Nearly all prostate cancers treated with hormonal therapy eventually become resistant to this treatment over a period of months or years. Some doctors believe that constant exposure to hormonal drugs might promote resistance, and recommend intermittent treatment with these drugs as an alternative. With intermittent therapy, hormonal drugs are stopped after a man's blood PSA level drops to a very low level and remains stable for a while. If the PSA level begins to rise, the drugs are started again. However, one advantage of intermittent treatment is that the side effects of hormonal therapy (such as impotence, hot flashes, and loss of sex drive) are avoided for a while.
Chemotherapy is used for patients whose prostate cancer has spread outside of the prostate gland and for whom hormone therapy has failed. This treatment is not expected to destroy all the cancer cells, but it may slow tumor growth and reduce pain. Chemotherapy is not recommended as a treatment for men with early prostate cancer.
Chemotherapy uses anticancer drugs that are injected into a vein or muscle, or are taken by mouth. These drugs kill cancer cells, but they also damage some normal cells. The doctor must maintain a delicate balance of chemotherapy doses, making them strong enough to kill the cancer cells but not strong enough to destroy many healthy cells.
For some patients with prostate cancer, the best choice may be expectant therapy with no immediate active treatment. Expectant therapy is also called watching and waiting, watchful waiting, observation, or deferred therapy. Watching and waiting may be recommended if a cancer is not causing any symptoms, is expected to grow very slowly, and is small and contained within one area of the prostate.
This approach is particularly suited for men who are elderly or have other serious health problems. Because prostate cancer often spreads very slowly, many older men who have the disease never need any treatment. Some other men choose watchful waiting because, in their view, the side effects of aggressive treatments outweigh their benefits. Expectant therapy does not mean that a man receives no medical care or followup. Rather, his cancer is regularly and carefully observed and monitored. Usually this approach includes a PSA blood test and digital rectal exam every six months, plus yearly transrectal ultrasound-guided biopsy of the prostate. If a man develops bothersome symptoms or his cancer begins to grow more quickly, decisions about active treatment can be reconsidered.
Risks associated with radical prostatectomy are similar to those of any major surgery. These include potential for heart attack, stroke, blood clots in the legs that may travel to the lungs, and infection at the incision site. In rare cases, death can occur as a result of this operation. The level of risk varies a great deal, depending, in part, on the patient's overall health condition and age.
The main side effects of radical prostatectomy are incontinence and impotence. Normal bladder control returns for many patients within several weeks or months after radical prostatectomy. Mild stress incontinence, which is passing a small amount of urine when coughing, laughing, sneezing, or exercising, may persist permanently after surgery in up to 35% of men. About 10% of patients have more serious stress incontinence, which may be permanent. About 2% of men report complete loss of bladder control and another 7% have frequent leakage of urine. About 20% use absorbent pads because of incontinence.
During the first 3 to 12 months after radical prostatectomy, most men will not be able to get a spontaneous erection and will need to use medications or other treatments if they wish to have an erection. The effect of this operation on a man's ability to achieve an erection is related to his age and whether nerve-sparing surgery was done. Nearly all men who have a radical prostatectomy should expect some decrease in their ability to have an erection, but younger men may expect to retain more of their ability. After standard radical prostatectomy, between 65% and 90% of men will become impotent, depending on their age.
Some studies have found that if surgery does not remove the nerves on either side of the prostate, the impotence rate is as low as 25% and 30% for men under 60. However, other studies have reported higher rates of impotence in similar patients. Impotence occurs in 70% to 80% of men over 70, even if nerves on both sides are not removed. If potency remains after surgery, the sensation of orgasm should continue to be pleasurable, but there is no ejaculation of semen. In other words, the orgasm is "dry."
It is important for you to have honest, open discussions with your cancer care team. They want to answer all of your questions, no matter how trivial you might think they are. For instance, consider these questions:
In addition to these sample questions, be sure to write down some of your own. For instance, you might want to ask about recovery times so you can plan your work schedule. If you are younger, you may want to discuss your plans for children should impotence or sterility occur. Or you may want to discuss survival rates for men with your stage of prostate cancer as related to various approaches to treatment. You also may want to ask about second opinions or about clinical trials for which you may qualify.
