What is the prostate gland?

The prostate gland is an organ that is located at the base or outlet (neck) of the urinary bladder. (See the diagram that follows.) The gland surrounds the first part of the urethra. The urethra is the passage through which urine drains from the bladder to exit from the penis. One function of the prostate gland is to help control urination by pressing directly against the part of the urethra that it surrounds. The main function of the prostate gland is to produce some of the substances that are found in normal semen, such as minerals and sugar. Semen is the fluid that transports the sperm to assist with reproduction. A man can manage quite well, however, without his prostate gland. (See the section on surgical treatment for prostate cancer.)

In a young man, the normal prostate gland is the size of a walnut (<30g). During normal aging, however, the gland usually grows larger. This hormone-related enlargement with aging is called benign prostatic hyperplasia (BPH), but this condition is not associated with prostate cancer. Both BPH and prostate cancer, however, can cause similar problems in older men. For example, an enlarged prostate gland can squeeze or impinge on the outlet of the bladder or the urethra, leading to difficulty with urination. The resulting symptoms commonly include slowing of the urinary stream and urinating more frequently, particularly at night. Patients should seek medical advice from their urologist or primary-care physician if these symptoms are present.

What is prostate cancer?

Prostate cancer is a malignant (cancerous) tumor (growth) that consists of cells from the prostate gland. Generally, the tumor usually grows slowly and remains confined to the gland for many years. During this time, the tumor produces little or no symptoms or outward signs (abnormalities on physical examination). However, all prostate cancers do not behave similarly. Some aggressive types of prostate cancer grow and spread more rapidly than others and can cause a significant shortening of life expectancy in men affected by them. A measure of prostate cancer aggressiveness is the Gleason score (discussed in more detail later in this article), which is calculated by a trained pathologist observing prostate biopsy specimens under the microscope.

As the cancer advances, however, it can spread beyond the prostate into the surrounding tissues (local spread). Moreover, the cancer also can metastasize (spread even farther) throughout other areas of the body, such as the bones, lungs, and liver. Symptoms and signs, therefore, are more often associated with advanced prostate cancer.

Why is prostate cancer important?

Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. According to the American Cancer Society's most recent estimates, 192,280 new cases of prostate cancer would be diagnosed in 2009 and 27,360 would die from the disease.

The estimated lifetime risk of being diagnosed with the disease is 17.6% for Caucasians and 20.6% for African Americans. The lifetime risk of death from prostate cancer similarly is 2.8% and 4.7% respectively. As reflected in these numbers, prostate cancer is likely to impact the lives of a significant proportion of men that are alive today.

Over the years, however, the death rate from this disease has shown a steady decline, and currently, more than 2 million men in the U.S. are still alive after being diagnosed with prostate cancer at some point in their lives.

Although it is subject to some controversy, many experts in this field, therefore, recommend that beginning at age 40, all men should undergo screening for prostate cancer.

What are prostate cancer causes?

The cause of prostate cancer is unknown, but the cancer is not thought to be related to benign prostatic hyperplasia (BPH). The risk (predisposing) factors for prostate cancer include advancing age, genetics (heredity), hormonal influences, and such environmental factors as toxins, chemicals, and industrial products. The chances of developing prostate cancer increase with age. Thus, prostate cancer under age 40 is extremely rare, while it is common in men older than 80 years of age. As a matter of fact, some studies have suggested that among men over 80 years of age, 50%-80% of them may have prostate cancer! More than 80% of prostate cancers are diagnosed in men older than 65 years of age.

As mentioned previously, African-American men are 1.6 times more likely than white men to develop prostate cancer. They are also 2.4 times more likely to die from their disease as compared to white men of a similar age. These differences in diagnosis and death rates are, however, more likely to reflect a difference in factors such as environmental exposure, diet, lifestyle, and health-seeking behavior rather than any racial susceptibility to prostate cancer. Recent studies indicate that this disparity is progressively decreasing with chances of complete cure in men undergoing treatment for organ-confined prostate cancer (cancer that is limited to within the prostate without spread outside the confines of the prostate gland), irrespective of race.

Genetics (heredity), as just mentioned, plays a role in the risk of developing a prostate cancer. Prostate cancer is more common among family members of individuals with prostate cancer. This risk may be two to three times greater than the risk for men without a family history of the disease. Earlier age at diagnosis (<60 years) in a first-degree relative (father or brother) and disease affecting more than one relative also increases the risk for developing prostate cancer.

Testosterone, the male hormone produced by the testicles, directly stimulates the growth of both normal prostate tissue and prostate cancer cells. Not surprisingly, therefore, this hormone is thought to be involved in the development and growth of prostate cancer. The important implication of the role of this hormone is that decreasing the level of testosterone should be (and usually is) effective in inhibiting the growth of prostate cancer.

Recent evidence has suggested that sexually transmitted infections are risk factors for developing prostate cancer. Men with a history of sexually transmitted infections have a 1.4 times greater chance of developing prostate cancer as compared men without this history.

Although still unproven, environmental factors, such as cigarette smoking and diets that are high in saturated fat, seem to increase the risk of prostate cancer. There is also a suggestion that obesity leads to an increased risk of having more aggressive, larger prostate cancer, which results in a poorer outcome after treatment. Additional substances or toxins in the environment or from industrial sources might also promote the development of prostate cancer, but these have not yet been clearly identified. Geographical influences also seem to play a role in the development of prostate cancer with men living in the Scandinavian and North American countries being at a higher risk for the disease as compared to those residing in Asian countries.

Of note, there is no proven relationship between the frequency of sexual activity and the chances of developing prostate cancer.

What are prostate cancer symptoms and signs?

In the early stages, prostate cancer often causes no symptoms for many years. As a matter of fact, these cancers frequently are first detected by an abnormality on a blood test (the PSA, discussed below) or as a hard nodule (lump) in the prostate gland. Occasionally, the doctor may first feel a hard nodule during a routine digital (done with the finger) rectal examination. The prostate gland is located immediately in front of the rectum.

Rarely, in more advanced cases, the cancer may enlarge and press on the urethra. As a result, the flow of urine diminishes and urination becomes more difficult. Patients may also experience burning with urination or blood in the urine. As the tumor continues to grow, it can completely block the flow of urine, resulting in a painfully obstructed and enlarged urinary bladder. These symptoms by themselves, however, do not confirm the presence of prostate cancer. Most of these symptoms can occur in men with non-cancerous (benign) enlargement of the prostate (the most common form of prostate enlargement). However, the occurrence of these symptoms should prompt an evaluation by the doctor to rule out cancer and provide appropriate treatment.

Furthermore, in the later stages, prostate cancer can spread locally into the surrounding tissue or the nearby lymph nodes, called the pelvic nodes. The cancer then can spread even farther (metastasize) to other areas of the body. Symptoms of metastatic disease include fatigue, malaise, and weight loss. The doctor during a rectal examination can sometimes detect local spread into the surrounding tissues. That is, the physician can feel a hard, fixed (not moveable) tumor extending from and beyond the gland. Prostate cancer usually metastasizes first to the lower spine or the pelvic bones (the bones connecting the lower spine to the hips), thereby causing back or pelvic pain. The cancer can then spread to the liver and lungs. Metastases (areas to which the cancer has spread) to the liver can cause pain in the abdomen and jaundice (yellow color of the skin) in rare instances. Metastases to the lungs can cause chest pain and coughing.

What about hormonal treatment for prostate cancer?

The male (androgenic) hormone is called testosterone. It stimulates the growth of cancerous prostatic cells and, therefore, is the primary fuel for the growth of prostate cancer. The idea of all of the hormonal treatments (medical and surgical), in short, is to decrease the stimulation by testosterone of the cancerous prostatic cells. Testosterone normally is produced by the testes in response to stimulation from a hormonal signal called LH-RH. The LH-RH stands for luteinizing hormone-releasing hormone and is also called gonadotropin-releasing hormone. This hormone comes from a control station in the brain and travels in the bloodstream to the testes. Once there, the LH-RH stimulates the testes to produce and release testosterone.

Hormonal treatment, also referred to as androgen deprivation (depriving the prostate of testosterone), can be accomplished surgically or medically. The surgical hormonal treatment is removal of the testes in an operation called an orchiectomy or a castration. This surgery thus removes the body's source of testosterone. The medical hormonal treatment involves taking one or two types of medication. One type is referred to as the LH-RH agonists. They work by competing with the body's own LH-RH. These drugs thereby inhibit (block) the release of LH-RH from the brain. The other type of drug is referred to as anti-androgenic, meaning that these drugs work against the male hormone. That is, they work by blocking the effect of testosterone itself on the prostate.

Today, most men electing hormonal treatment choose medication over surgery, probably because they view surgical castration as more devastating cosmetically or psychologically. Actually, however, the effectiveness and side effects of medical hormonal treatment as compared to surgical hormonal treatment are very much the same. Both types of hormonal treatment usually effectively eliminate stimulation of the cancer cells by testosterone. Some tumors of the prostate, however, do not respond to this form of treatment. They are referred to as androgen-independent prostate cancers. The principal side effects of all of these hormonal treatments (that is, the side effects of androgenic deprivation) are enlarged breasts (gynecomastia) that often are tender, flushing (like hot flashes), and impotence.

The LH-RH agonists, leuprolide (Lupron) or goserelin (Zoladex), are given as monthly injections in the doctor's office. The anti-androgenic drugs, flutamide (Eulexin) or bicalutamide (Casodex), are oral capsules that are used usually in combination with the LH-RH agonists. The LH-RH agonists are often effective alone. The anti-androgenic drugs are added, however, if the cancer progresses despite the use of the LH-RH agonists. The hormonal treatments may have value, as well, when combined with radiation therapy. Current evidence suggests that hormonal therapy enhances the therapeutic effect of radiation.

Generally, hormonal treatment is reserved for individuals who have advanced prostate cancer with local spread or metastases. Occasionally, an individual with organ-confined (localized) prostate cancer will receive hormonal treatment because he has severe associated medical problems or simply because he refuses to undergo surgery or radiation. Hormonal treatment is used in less than 10% of men with organ-confined (localized) prostate cancer. Remember that the intent of hormonal therapy usually is palliative. This means that the goal is to control the cancer rather than cure it because a cure is not possible.