Prostate Cancer

In the United States, prostate cancer is one of the most common cancers in men and the second most common cause of cancer death (exceeded only by lung cancer). The chance of developing prostate cancer increases with aging. More than three fourths of men with prostate cancer are 65 or older when cancer is diagnosed. The risk is highest among African Americans and Hispanics and among men whose close relatives had prostate cancer.

The cause of prostate cancer is not known. Prostate cancer commonly begins as a small lump in the prostate gland. Male hormones, especially testosterone, stimulate the growth of prostate cancer. The cancer usually grows very slowly and may take decades to produce symptoms. In many men, prostate cancer never produces symptoms. Many men die from some other cause without ever knowing that they had prostate cancer. But in some men, the cancer is more aggressive so that it grows rapidly and spreads outside the prostate.

Prostate cancer can spread directly to nearby structures, such as the urethra or bladder. When the cancer spreads beyond the region of the prostate, it most commonly spreads to bones, especially vertebrae and ribs; it may spread to the brain.

Symptoms

Prostate cancer usually causes no symptoms until it reaches a late stage. Sometimes, symptoms similar to those of benign prostatic hyperplasia (BPH) develop, including difficulty starting or continuing urination and a need to urinate frequently or urgently. However, these symptoms do not develop until the cancer is large enough to compress the urethra and partially block the flow of urine or irritate the bladder muscle. Some men have bloody urine.

Sometimes, symptoms develop after the cancer spreads. Pain develops when prostate cancer spreads to bone. Bones may weaken enough to easily fracture. Cancer that spreads to vertebrae can compress the spinal cord, resulting in pain, numbness, leg weakness, or incontinence. Cancer that spreads to the skull can compress brain tissue, resulting in seizures, confusion, headaches, and weakness, among other symptoms. When cancer spreads to bone marrow, production of red blood cells decreases, resulting in anemia, with symptoms such as fatigue and weakness.

Screening

Because prostate cancer is common, many doctors check for it in men with no symptoms (screening). However, experts disagree about the role of screening. Screening seems to offer the advantage of finding more prostate cancers early—when they are most likely to be curable. However, since prostate cancer may grow very slowly in many men, screening may find many cancers that might never cause symptoms or death. Treating a slow-growing cancer might be more damaging than leaving the cancer untreated. Newer tests are being developed to help doctors identify cancers that are more likely to grow quickly.

Screening tests are not foolproof. They may suggest the possibility of prostate cancer in men who do not actually have prostate cancer. In other words, they may give false-positive results. Tests, such as biopsies, are then done to try to find the cancer. These tests can be stressful and carry some risk.

To screen for prostate cancer, a doctor performs a digital rectal examination. A gloved finger is inserted into the man's rectum to feel the surface of the prostate gland. If the man has prostate cancer, a doctor sometimes feels a hard bump in the prostate. Another screening test involves measuring the level of prostate-specific antigen (PSA) in a sample of blood. PSA is a substance that is usually higher in men with prostate cancer. PSA levels tend to increase with aging, but cancer increases the PSA levels even more. Also, PSA levels are higher than normal in men with BPH or inflammation and infection of the prostate (prostatitis). Unfortunately, because some prostate cancers do not produce PSA, screening with only a PSA test is unreliable.

Diagnosis

If the results of a digital rectal examination or PSA test suggest prostate cancer, a biopsy is done. In a biopsy, tissue samples from the prostate are taken and examined under a microscope. Usually, a doctor first obtains images of the prostate by inserting an ultrasound transducer, or probe, into the rectum (transrectal ultrasound). Then tissue samples are taken from the prostate using a needle inserted through the probe. This procedure takes only a few minutes. A local anesthetic helps control pain.

Two features help a doctor determine the likely course and the best treatment of the cancer: how distorted (malignant) the cells look under a microscope (grading) and how far the cancer has spread (staging).

Grading usually involves microscopic examination and biochemical tests of the tissue samples. Doctors look to see how distorted the overall gland is and how abnormal the cancer cells appear and determine the Gleason score. The score helps rate the aggressiveness of prostate cancer. Those cancers that are most distorted tend to grow and spread quickly and have a higher Gleason score (8 or higher). Those that are less likely to grow quickly and spread have a lower Gleason score (5 or lower). This is true regardless of the man's age.

Staging involves tests to assess how far the cancer has spread. Doctors perform an examination to determine whether the cancer has spread within the prostate, to lymph nodes in areas near the prostate, or to organs far from the prostate. Testing may not be necessary when the likelihood of spread beyond the prostate is extremely low. Results of the digital rectal examination, ultrasound scan, and biopsy reveal how far the cancer has spread within the prostate. Computed tomography (CT) or radiolabeled antibody nuclear scans of the pelvis help detect spread to the lymph nodes. A bone scan reveals spread to bone. If doctors suspect that cancer has spread to certain sites, CT or MRI may be done.

Treatment

Choosing among treatment options can be complicated and often depends on the man's lifestyle preferences and life expectancy. Current treatments are not without side effects, which may affect quality of life. For example, surgery to remove the prostate, radiation therapy, and hormone therapy can result in involuntary loss of urine (urinary incontinence) and erectile dysfunction (impotence). When choosing among treatment options, men need to weigh the advantages and disadvantages.

Treatment strategies: Treatment for prostate cancer usually involves one of three strategies: watchful waiting, curative treatment, or palliative therapy.

• Watchful waiting foregoes treatment until symptoms develop, if they develop at all. This strategy is best for men whose cancers are unlikely to spread, cause symptoms, or affect life expectancy. For example, most low grade cancers confined to a small area within the prostate grow very slowly. These cancers usually do not spread for many years. Men over 80 years of age are most likely to choose watchful waiting, particularly if they have other medical problems, because older men are far more likely to die of other diseases before such cancers cause symptoms. During watchful waiting, symptoms can be treated if necessary. Periodic testing may be done to see if the cancer is growing rapidly or spreading. The man may later decide to pursue curative treatment if testing shows growth or spread.
• Curative treatment is a common strategy for men with cancers confined to the prostate that are likely to cause troublesome symptoms or death. Curative treatment approaches are surgery or radiation. High grade or rapidly growing cancers are more commonly treated. Curative treatment may also help men with small, slowly growing cancers (even though symptoms from such cancers may not develop until a decade later) if the man expects to otherwise live many years. Curative treatment for cancers that have spread outside the prostate is difficult unless the extent of the spread can be clearly identified. For example, cancers confined or adjacent to the prostate are more likely to be successfully treated. Side effects of curative treatment, which may include urinary incontinence and erectile dysfunction, can affect quality of life. Incontinence and erectile dysfunction are sometimes permanent.
• Palliative therapy aims at treating the symptoms rather than the cancer itself. This strategy is best suited to men with widespread prostate cancer that is not curable. The growth or spread of such cancers can usually be slowed or even temporarily reversed, relieving symptoms. Since these treatments cannot cure the cancer, symptoms eventually worsen. Death from the disease eventually follows.

Four forms of treatment are used in curative or palliative strategies for prostate cancer: surgery, radiation therapy, hormone therapy, and chemotherapy. Combinations and sequential use of these treatments are common.

Surgery: Surgical removal of the prostate (prostatectomy) is useful for cancer confined to the prostate. Surgery is less effective in curing fast-growing cancers, because they are more likely to have already spread by the time the cancer is diagnosed. Prostatectomy requires general anesthesia, a hospital stay, and a surgical incision, but only one procedure is needed.

There are two types of surgery to remove the prostate: radical prostatectomy and nerve-sparing prostatectomy. In radical prostatectomy, the entire prostate, the seminal vesicles, and part of the vas deferens are removed. Radical prostatectomy causes erectile dysfunction in many men, and urinary incontinence in some, yet it is more likely to cure prostate cancer. Men over 65 are less likely to have radical prostatectomy because they have a greater likelihood of having chronic diseases that shorten their life expectancy.

In nerve-sparing prostatectomy, some of the nerves needed to achieve erection are preserved, reducing the risks of erectile dysfunction (and incontinence). This procedure can be used if the surgeon sees that the cancer has not invaded the nerves and blood vessels. Nerve-sparing radical prostatectomy can be done using a type of endoscope (a flexible viewing tube) called a laparoscope. Alternatively, the surgery can be performed with computer-controlled robotic arms. Laparoscopic and robot-assisted techniques require a smaller incision and produce less postoperative pain, but they are offered only at major referral centers.

Radiation therapy: Radiation therapy can cure cancers that are confined to the prostate, as well as some cancers that have invaded nearby tissues. Radiation therapy cannot cure cancer that has spread to distant organs, including bone. However, radiation therapy can relieve pain that results from the spread of prostate cancer to bone.

Whereas surgery is accomplished in one procedure, radiation therapy usually requires many separate treatment sessions over the course of several weeks. During traditional radiation therapy (external beam radiation), a machine sends beams of radiation to the prostate and surrounding tissues. Treatments are usually given 5 days per week for 5 to 7 weeks.

Although erectile dysfunction can develop after radiation therapy, it is slightly less likely than after surgery. Urinary incontinence occasionally results. Urethral strictures—scars that narrow the urethra and interfere with the flow of urine—can develop. Other troublesome but usually temporary side effects of traditional radiation therapy include burning during urination, having to urinate frequently, blood in the urine, irritation and inflammation of the rectum and diarrhea (radiation proctitis), and sudden urges to defecate.

With recent technical advances, doctors can more precisely focus the radiation beam on the cancer (a procedure called three-dimensional conformal radiotherapy). Conformal radiotherapy causes fewer temporary side effects, particularly radiation proctitis.

Radiation can also be delivered by inserting radioactive implants into the prostate (brachytherapy). Implants are placed using images obtained from ultrasound or CT scans. Brachytherapy offers some advantages: it can deliver high doses of radiation to the prostate while sparing healthy surrounding tissues and producing fewer side effects. Brachytherapy can be performed in a few hours, does not require repeated treatment sessions, and uses only spinal anesthesia. Brachytherapy is not appropriate for all men. Combined treatment with brachytherapy and traditional radiation therapy is sometimes recommended.

Hormone-blocking therapy: Because prostate tissue tends to grow more quickly in the presence of testosterone, reducing testosterone levels tends to slow cancer growth. Hormone-blocking therapy can be effective in men in whom surgery and radiation therapy have failed. Hormone-blocking therapy is also effective when used before radiation therapy, and it is now routinely used this way. It is not effective when used before surgery. Hormone-blocking therapy is not curative, and cancer recurs in all men in whom other therapies have failed.

Hormone-blocking drugs used to treat prostate cancer in the United States include leuprolide and goserelin, which prevent the pituitary from stimulating the testes to make testosterone. A doctor injects these drugs periodically, usually for the rest of the man's life. Other drugs that block testosterone's effects (such as flutamide, bicalutamide, and nilutamide) may also be used. These drugs are taken daily by mouth.

Testosterone levels can also be reduced by surgically removing the testes. This treatment is very effective, but many men do not want to undergo such a body-altering treatment.

Low testosterone levels that result from hormone-blocking drugs can produce hot flashes, thinning and weakening of bones, loss of energy, reduced muscle mass, fluid retention, reduced libido, reduced body hair, erectile dysfunction, and breast enlargement (gynecomastia). In an effort to reduce these symptoms, hormone-blocking therapy is sometimes given intermittently instead of continuously.

Chemotherapy: Chemotherapy may be used for cancers that have spread beyond the prostate. Treatment that combines chemotherapy with other approaches improves survival in men with aggressive, later-stage cancers.

The introduction of bisphosphonate therapy (zoledronic acid) has greatly improved care for men in whom prostate cancer has spread to bones. Bisphosphonates interfere with cells (osteoclasts) in bones that are activated by cancer cells, thereby reducing bone destruction and the likelihood of fractures.