Prostate Cancer

The Gleason Grade Group system is the most common way to grade prostate cancer (previously the Gleason Scoring system was used). Based on the microscopic examination of tissues obtained from the biopsy, a number is assigned based on how distorted the cells appear. The current version of this scoring system gives each cancer a grade between 1 and 5, while the older Gleason Scoring system assigned a score between 6 and 10. The higher the number (high grade), the more aggressive the cancer is and the more likely it is that the cancer will spread.

Gleason Grade Group 1 = Gleason Score 6 (3+3)

Gleason Grade Group 2 = Gleason Score 7 (3+4)

Gleason Grade Group 3 = Gleason Score 7 (4+3)

Gleason Grade Group 4 = Gleason Score 8

Gleason Grade Group 5 = Gleason Score 9 and 10

Gleason Grade, PSA level, and clinical stage together predict the prognosis better than any of them alone and help guide appropriate treatment decisions.

Prostate cancers are staged according to 3 criteria:

• How far the cancer has spread within the prostate

• Whether the cancer has spread to lymph nodes in areas near the prostate

• Whether the cancer has spread to bones or other organs far from the prostate (metastatic cancer)

Testing to stage the cancer is often done when cancer is diagnosed. However, such testing may not be necessary when the likelihood of spread beyond the prostate is extremely low. Likelihood of spread is low when cancers have a Grade Group of 2 or less, the PSA level is less than 10 ng/mL (10 mcg/L), and the cancer has not penetrated the surface of the gland. Results of the digital rectal examination, ultrasonography, and biopsy reveal how far the cancer has spread within the prostate.

If likelihood of spread is not low, doctors usually do computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis. Sometimes an MRI of the prostate is done using a special coil inserted in the rectum. A nuclear medicine (NM) bone scan may be done in people who have pain in their bones or who have a very high prostate-specific antigen (PSA) or high Gleason Grade Group.

If spread to the brain or spinal cord is suspected, CT or MRI of those organs is done.

Treatment for prostate cancer usually involves one of 3 strategies based on the aggressiveness of the cancer and how far the cancer has spread:

• Active surveillance

• Curative treatment

• Palliative treatment

Active surveillance means doctors give no treatment unless the cancer is progressing or changing. The advantage of this strategy is avoiding or postponing the potential side effects of treatment. Active surveillance should be considered for men whose cancers are unlikely to spread or cause symptoms. For example, most cancers that are confined to a small area within the prostate and have low Gleason Grade Group grow very slowly. Thus, older men, particularly those who have other serious health problems, are far more likely to die of other causes before such cancers kill them or cause symptoms. In younger men, particularly those who are healthy, even a slow-growing cancer may eventually cause problems. In such men, active surveillance may be less preferred but should still be considered. During active surveillance, doctors periodically ask about symptoms, measure the PSA level, do digital rectal examinations, and repeat biopsies (with or without MRI guidance) to determine whether the cancer is causing symptoms, growing rapidly, or spreading. If testing shows growth or spread, doctors offer curative or palliative treatment.

Curative treatment aims to remove or kill all of the cancer and includes

• Surgery

• Radiation therapy

• Less often, cryotherapy (freezing), high-frequency ultrasound

Curative (also called definitive) treatment is a common strategy for men with cancers confined to the prostate that are likely to cause troublesome symptoms or death. Such cancers include those that are growing rapidly as well as some small, slowly growing cancers in men who are likely to live for some time (perhaps at least 10 or 15 years). Such men are typically those who are healthy, younger (particularly those under 60), or both. Curative treatment is not pursued if cancer has spread widely, but it can benefit some men with cancers that have spread to the area just outside the prostate. Such cancers are likely to cause symptoms within a relatively short period. However, curative treatment is most likely to be successful with cancers that are still confined to the area near the prostate. Curative treatment can prolong life and reduce or eliminate severe symptoms resulting from some cancers. Side effects, although less common with newer treatments, can still develop and diminish quality of life. These can include, for example, erectile dysfunction and, less often, urinary incontinence (most often as a result of surgery) and pain or bleeding during defecation and irritation or bleeding when urinating (as a result of radiation therapy).

Palliative treatment aims to treat the symptoms rather than cure the cancer. Palliative therapies include

• Hormonal therapy

• Chemotherapy

• Radiation therapy

Palliative treatment is best suited to men with widespread prostate cancer, which is not curable. The growth or spread of such cancers can usually be slowed or temporarily reversed, relieving symptoms. Besides trying to slow the cancer’s growth and spread, doctors may try to relieve symptoms resulting from the effects of cancer in other organs and tissues (such as the bones). However, because these treatments cannot cure the cancer, symptoms eventually worsen. Death due to the disease eventually follows.

Surgically removing the prostate (prostatectomy) is useful for cancer that is confined to the prostate. Prostatectomy is usually not done if staging tests show the cancer has spread. Prostatectomy is very effective in curing low-grade, slowly growing cancers but is less effective in high-grade, fast-growing cancers. Such cancers are more likely to have spread even if spread is not detectable with staging tests at the time of diagnosis.

Prostatectomy requires general or spinal anesthesia, an overnight hospital stay, and a surgical incision. Following surgery, men must have a catheter in their penis for a week or 2 until the connection between the bladder and urethra heals. Doctors do not routinely give chemotherapy or hormone therapy before or after surgery. In men whose prostate cancer is found to be aggressive (high-grade, fast-growing) at the time of surgery and whose PSA increases, consideration is being given to radiation therapy (with hormone therapy) after surgery.

Prostatectomy may lead to permanent erectile dysfunction and urinary incontinence. Erectile dysfunction may occur because the nerves to the penis that control erection run across the prostate and may be damaged during surgery. Incontinence may occur because part of the sphincter that closes the opening at the bottom of the bladder must be removed during surgery. However, most men recover continence within 6 months following prostatectomy. Erectile function recovery is more variable, depending in part on men's erectile function prior to surgery, the aggressiveness of the prostate cancer, and the surgical technique.

Techniques for doing prostatectomy include open radical prostatectomy and laparoscopic or robot-assisted radical prostatectomy. In open radical prostatectomy, the entire prostate, the seminal vesicles, and part of the vas deferens are removed through an incision in the lower abdomen or, rarely, in the area between the scrotum and anus. Lymph nodes may also be removed to check for cancer. In laparoscopic or robot-assisted laparoscopic radical prostatectomy, the same structures are removed, but these procedures are done through smaller incisions and result in less postoperative pain and blood loss and typically a faster recovery.

Radical prostatectomy, irrespective of technique, is the surgery done when trying to cure prostate cancer. More than 90% of men with cancer confined to the prostate live at least 10 years after radical prostatectomy. Younger men who can otherwise expect to live at least 10 to 15 more years are most likely to benefit from radical prostatectomy. However, the procedure causes some leakage of urine in up to 10% of men. Temporary incontinence develops in most men and may last for several months. Incontinence is less likely in younger men.

Prostate Removal

video

A degree of erectile dysfunction develops in most men after radical prostatectomy, particularly in those who experience difficulty with erections before surgery. Usually prostatectomy can be done in such a way that some of the nerves needed to achieve erection are spared—this procedure is called nerve-sparing radical prostatectomy. This procedure cannot be used to treat cancer that has invaded the nerves and blood vessels of the prostate. Nerve-sparing radical prostatectomy is less likely than non–nerve-sparing radical prostatectomy to cause erectile dysfunction. Most men are diagnosed early and, thus, can be treated with nerve-sparing radical prostatectomy.

Blockage of urine flow caused by narrowing of part of the bladder or scarring of the urethra (urethral stricture) develops in 7 to 20% of men. Blockage can usually be easily treated (see Urinary Tract Obstruction: Treatment).

Radiation therapy may cure cancers that are confined to the prostate, as well as cancers that have invaded tissues around the prostate. Although radiation therapy cannot cure cancer that has spread to distant organs, it can help relieve the pain resulting from the spread of prostate cancer to bone.

Doctors sometimes give radiation therapy after surgery to treat the areas around the prostate or if PSA is found in the blood after surgery. PSA in the blood after surgery suggests that surgery has not removed all of the cancer.

For many stages of prostate cancer, 10-year survival rates after radiation therapy are nearly as high as those achieved with surgery. More than 90% of men with cancer confined to the prostate live at least 10 years after undergoing radiation therapy. Radiation therapy can be delivered as

• External beam radiation therapy (used to treat cancer within the prostate gland and prostate cancer that has spread to bone)

• Radioactive implants (used to treat low-risk cancer within the prostate gland but not prostate cancer that has spread to bone)

• Radium-223 (an intravenous agent used to treat prostate cancer that has spread to bone, but not cancer within the prostate gland)

External beam radiation therapy uses a machine to send beams of radiation to the prostate and surrounding tissues. Computed tomography (CT) is often used to help focus the radiation beams more precisely on the cancer by precisely identifying the structures affected. This approach is called three-dimensional conformal radiation therapy. Treatments are usually given 5 days per week for 7 to 8 weeks. Although some degree of erectile dysfunction can occur in up to 40% of men, it is less likely to develop during the period soon after radiation therapy than during the period soon after prostatectomy. However, after months or years, erectile dysfunction seems to be as likely after radiation therapy as after prostatectomy. Incontinence is rare when three-dimensional conformal radiation therapy is used. IMRT (intensity-modulated radiation therapy) and SBRT (stereotactic body radiation therapy) are modifications of standard radiation therapy. Sometimes, for more aggressive cancers, doctors also give hormonal therapy for up to 2 or 3 years in addition to the radiation therapy.

Scars that narrow the urethra and impede the flow of urine (urethral strictures) develop in about 5 to 10% of men treated with external beam radiation therapy. Other troublesome but usually temporary side effects include burning during urination, having to urinate frequently, blood in the urine, diarrhea that is sometimes bloody, radiation proctitis (usually causing irritation of the rectum and diarrhea), and sudden urges to defecate. Rarely, men develop cancers in the surrounding organs (bladder, rectum) caused by radiation therapy.

A different form of external beam radiation therapy is proton beam therapy, which uses a different form of radiation that allows the radiation to be delivered more precisely to cancer cells while avoiding healthy cells. Proton beam therapy has been shown to be beneficial for other cancers, but it is not clear if it has fewer side effects in prostate cancer than standard external beam radiation therapy.

Recent advances in prostate cancer radiation therapy include

• Placing markers around the prostate to improve targeting

• Using a transrectal needle to place hydrogel spacers in the rectum to reduce radiation's toxic effects (these hydrogel spacers eventually break down and are resorbed into the tissues)

• Dividing large doses of radiation up over time and administering them over a shorter period of time (fewer days or weeks) than traditional radiation

Radioactive implants can be inserted into the prostate (brachytherapy). The implants are small, seedlike pieces of radioactive material. Doctors inject the implants into the prostate gland through the area between the scrotum and anus using ultrasonography or CT to guide placement. Brachytherapy can be done in less than 2 hours, does not require repeated treatment sessions, and can be done using spinal anesthesia. Brachytherapy also can deliver high doses of radiation to the prostate while often sparing healthy surrounding tissues and causing fewer side effects. However, brachytherapy may cause urethral strictures in up to 10% of men. The radioactivity of the seeds decreases with time. Seeds may later be passed in the urine. Men treated with these seeds should avoid close contact with pregnant women and young children for a period of time after the procedure because the radioactivity can be harmful to a fetus or young child. Cure rates 10 to 15 years after brachytherapy are similar to rates obtained with other treatments for some men. Combined treatment with brachytherapy and external beam radiation therapy is sometimes recommended for more aggressive cancers. Temporary brachytherapy implants (requiring an overnight hospital stay) are available at some centers.

Radium-223 is a drug given intravenously that emits a particular type of radiation (alpha radiation). Unlike beam radiation and brachytherapy, it is not directed at a particular target. Radium-223 is used to treat bone metastases from prostate cancer rather than the prostate cancer in the prostate gland. Once in the bloodstream, radium-223 seeks out areas of bone affected by prostate cancer, where it helps destroy cancer cells. Because it targets bone tissue and does not scatter radiation (like radiation beams or seeds), it may spare nearby tissues from radiation damage.

High-intensity focused ultrasound (HIFU) uses intense ultrasound energy administered through a probe placed in the rectum to destroy prostate tissue. It has been used for many years in Europe and Canada and has recently become more widely available in the United States. The role of this technology in the management of prostate cancer is still evolving. HIFU is best suited for treating prostate cancer that recurs after surgery and low-risk cancers in which individual tumors can be treated by focal therapy (an imaging-guided technique for directly destroying the cancerous tissue with either lasers or electricity).

Cryotherapy is the destruction of prostate cancer cells by freezing, which is accomplished by using a cryoprobe to deliver argon gas to the cancerous tissue, followed by thawing. Cryotherapy is not the therapy of choice in the United States, but it may be used if radiation therapy is unsuccessful. Side effects of the procedure include blockage of urinary flow from the bladder (bladder outlet obstruction), urinary incontinence, erectile dysfunction, and rectal pain or injury.

Because most prostate cancers require testosterone to grow or spread, treatments that block the effects of this hormone (hormonal therapy) can slow progression of the tumors. Hormonal therapy is commonly used to delay the spread of the cancer that has come back after surgery or radiation therapy or to treat widespread (metastatic) prostate cancer. Hormonal therapy is sometimes combined with other treatments such as radiation therapy. Hormonal therapy is not curative on its own but can prolong life as well as decrease symptoms. Eventually, however, hormonal therapy is likely to lose effectiveness, and the disease progresses.

testosterone

Medications that block testosterone

Side effects of hormonal therapy may include hot flashes, osteoporosis, loss of energy, reduction in muscle mass, fluid weight gain, reduction of libido, decrease in body hair, erectile dysfunction, and breast enlargement (gynecomastia).

The oldest form of hormonal therapy involves the removal of both testes (bilateral orchiectomy). The effects of bilateral orchiectomy on testosterone

In men with widespread prostate cancer, hormonal therapy may become ineffective after a few years. When cancer eventually progresses despite hormonal therapy, men may live only a few more years.

Cancer that does not respond to hormonal therapy that successfully decreases testosterone levels is called castrate-resistant prostate cancer (CRPC).

After all forms of treatment, PSA levels are measured at regular intervals (usually every 3 to 4 months for the first year, and then every 6 months for the rest of the man’s life). By 1 month after surgery, PSA should not be detected. Following radiation therapy, PSA decreases more slowly and usually does not become undetectable but should remain stable at a low level. Increases in the PSA level may indicate that the cancer has recurred.