Adenocarcinoma of the prostate is the clinical term for a cancerous tumor on the prostate gland. As prostate cancer grows, it may spread to the interior of the gland, to tissues near the prostate, to seminal vesicles (sac-like structures attached to the prostate), and to distant parts of the body (e.g., bones, liver, lungs). Prostate cancer confined to the gland often is treated successfully.

Anatomy
The prostate gland is located in the pelvis, below the bladder, above the urethral sphincter and the penis, and in front of the rectum in men. It is made up of glandular tissue and muscle fibers that surround a portion of the urethra. The gland is covered by a membrane (prostate capsule) that produces prostate-specific antigen.

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The risk for developing prostate cancer rises significantly with age, and 60% of newly diagnosed cases occur in men over the age of 70.

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A family history of prostate cancer increases the risk. Other possible risk factors include the following:

• 55 years old and older
• Diet high in saturated fat
• Exposure to heavy metals (e.g., cadmium)
• Race (African American)
• Sedentary lifestyle
• Smoking

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Early prostate cancer usually is discovered during a routine digital rectal examination (DRE).

Symptoms are often similar to those of benign prostatic hyperplasia. Men observing the following signs and/or symptoms should see their physician for a thorough examination.

• Blood in the urine or semen
• Frequent urination, especially at night
• Inability to urinate
• Nagging pain or stiffness in the back, hips, upper thighs, or pelvis
• Painful ejaculation
• Pain or burning during urination (dysuria)
• Weak or interrupted urinary flow

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Digital rectal examination (DRE)
In a DRE, the physician inserts a lubricated, gloved finger into the rectum to feel the surface of the prostate gland. Healthy prostate tissue is soft, like the fleshy tissue of the hand where the thumb joins the palm. Malignant tissue is firm, hard, and often asymmetrical or stony, like the bridge of the nose. However, as many as one-third of patients diagnosed with prostate cancer have a normal DRE.

Transrectal ultrasound (TRUS)
TRUS is used to measure the size of the prostate and visually identify tumors. A probe inserted into the rectum emits ultrasonic impulses against the prostate. The images are projected on a monitor, so the physician can examine the gland and surrounding tissue for tumors.

TRUS and the digital rectal examination are effective prostate-cancer screening tools.

PSA and PAP Tests
Blood tests taken to check the levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP) in a patient who may have benign prostatic hyperplasia help the physician eliminate or confirm a diagnosis of prostate cancer.

Prostate-specific antigen (PSA) is produced by the cells of the prostate capsule (membrane covering the prostate) and periurethral glands. Patients with benign prostatic hyperplasia (BPH) or prostatitis produce greater amounts of PSA. The PSA level also is determined in part by the size and weight of the prostate.

The test measures the amount of PSA in the blood in nanograms per milliliter (ng/mL). A PSA of 4 ng/mL or lower is considered normal; 4 – 10 ng/mL, slightly elevated; 10 – 20, moderately elevated; and 20 – 35, highly elevated. Most men with slightly elevated PSA levels do not have prostate cancer, and many men with prostate cancer have normal PSA levels. A highly elevated level may indicate the presence of cancer.

The PSA test can produce false results. A false positive result occurs when the PSA level is elevated and there is no cancer. A false negative result occurs when the PSA level is normal and there is cancer. Because of this, a biopsy is usually performed to confirm or rule out cancer when the PSA level is high.

Free and total PSA (also known as PSA II)
PSA in the blood may be bound molecularly to one of several proteins or may exist in a free, or unbound, state. Total PSA is the sum of the levels of both forms; free PSA measures the level of unbound PSA only. Studies suggest that malignant prostate cells produce more bound PSA; therefore, a low level of free PSA in relation to total PSA might indicate a cancerous prostate, and a high level of free PSA compared to total PSA might indicate a normal prostate, BPH, or prostatitis.

Age-specific PSA
Evidence suggests that the PSA level increases with age. A PSA of up to 2.5 ng/mL for men age 40–49 is considered normal, as is 3.5 ng/mL for men age 50–59, 4.5 ng/mL for men age 60–69, and 6.5 ng/mL for men 70 and older. The use of age-specific PSA levels is not endorsed by all medical professionals.

Prostatic acid phosphatase (PAP) test
Prostatic acid phosphatase is an enzyme produced by prostate tissue. The level of PAP increases as prostate disease progresses.

Tumor Biopsy
If a tumor is found, a biopsy is performed to determine the type of cancer, its location, and stage of development.

Before undergoing the biopsy, patients should abstain from alcohol, aspirin, and nonsteroidal anti-inflammatory drugs (e.g., ibuprofen) for 1 week. They are required to take one Fleet enema the night before the procedure and one 2 hours before the biopsy. An oral antibiotic (usually ciprofloxacin) is prescribed to be taken the day before, the day of, and 2 days after the biopsy.

The biopsy is performed with the patient lying on his side with his knees brought up to his chest. A biopsy needle, similar to one used to draw blood or administer injections, is inserted through the perineum into the tumor. A probe, guided by transrectal ultrasound (TRUS), is inserted into the rectum to help the physician properly place the needle, which is projected through the tip of the probe. A cell sample is extracted from one or several areas of the tumor into the syringe. The sample(s) is analyzed by a pathologist to confirm the diagnosis of a cancerous tumor and determine its type. The results are obtained within 5–10 working days.

Gleason score
The biopsy sample(s) is examined under a microscope for cells or groups of cells that are markedly different from healthy tissue. The greater the disparity between the healthy cells and those that are malignant, the more likely the tumor is aggressive and will spread (metastasize).

The pathologist examines two tissue samples taken from different areas of the tumor and assigns a score of 1 to 5 to each sample. The more abnormal the tissue, the higher the score. The sum of the two produces the Gleason score. Gleason scores of 2 to 4 indicate that the cells are well differentiated, meaning the tissue is not too abnormal; 5 to 7 moderately differentiated; 8 to 10 poorly differentiated. Higher scores suggest aggressive tumors that likely require aggressive treatment.

Complications
After a biopsy, blood in the urine (hematuria) and stool is common and usually diminishes within 1–2 weeks. Patients also experience a dull ache in the perineum for several days. Men are advised to refrain from sexual intercourse for 3–5 days. Blood may appear in the semen.

If the patient develops a large number of blood clots or cannot urinate, the physician should be contacted or the patient should go to the emergency room.

Rarely, biopsy of a cancerous tumor also may cause spreading, or "seeding," of cancer cells along the path of the biopsy needle.

Computed tomographic (CT) scan
Computer-assisted tomography (CAT scan or CT scan) is an x-ray procedure that produces three-dimensional images of internal organs and glands. It can be used to detect pelvic lymph nodes enlarged by cancer, but results may be insufficient for diagnosis. CT scans are used only when tumors are large or PSA levels are high.

Bone scan
A bone scan is a nuclear imaging procedure that is used to detect metastasis to bones. It is not used in patients with small cancers and low PSA levels.

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The physician "stages" the tumor based on its size, the character of its cells, and the extent of metastisis. Two systems commonly are used for staging prostate cancer: the Jewett-Whitmore system and the TNM (tumor, node, metastases) system.

Jewett-Whitmore system

In the Jewett-Whitmore system, prostate cancer is classified first as stage A, B, C, or D. Stages A and B cancers are considered curable. Stages C and D are treatable, but their prognoses are discouaging. A number is then assigned to describe specific conditions within each stage. For example, a tumor classified as stage B1 is a single cancerous nodule confined to one lobe of the prostate.

 

Stage A Very early and without symptoms; cancer cells confined to the prostate A1 - Well differentiated and slightly abnormal cancer cells A2 - Moderately or poorly differentiated and abnormal cancer cells in several locations within the prostate

Stage B Confined to the prostate, but palpable (detectable by digital rectal exam) and/or detectable by elevated PSA B0 - Confined to the prostate, nonpalpable; PSA elevated B1 - Single cancerous nodule in one lobe of the prostate B2 - Extensive, involvment in one or both prostate lobes

Stage C Cancer cells found outside the prostate capsule (membrane covering the prostate); spread confined to surrounding tissues and/or seminal vesicles C1 - Extends outside the prostate capsule C2 - Bladder or urethral obstruction

Stage D Metastasis (spread) to regional lymph nodes, or to distant bones, organs (e.g., liver, lungs), and/or other tissues D0 - Metastatic, clinically localized, and showing elevated blood PAP levels D1 - Regional lymph nodes involved D2 - Distant lymph nodes, bones, or organs involve D3 - Metastatic disease after treatment

TNM System

The TNM (tumor, node, metastases) system stages are similar to those of the Jewett-Whitmore system, but with more specific alphanumeric subcategories.

Primary tumor (T)

TX	Tumor cannot be assessed
T0	No evidence of primary tumor
T1	Clinically not palpable or visible by imaging
T1a	Found incidental to other surgery; present in 5% or less of tissue
T1b	Found incidental to other surgery; present in 5% or more of tissue
T1c	Identified by needle biopsy
T2	Tumor confined within prostate
T2a	Involving half a lobe or less of prostate
T2b	Involving half a lobe
T2c	Involving both lobes
T3	Tumor extends through prostate capsule
T3a	Extends through one lobe
T3b	Extends through both lobes
T3c	Extends into seminal vesicles
T4	Involves structures other than seminal vesicles
T4a	Invades bladder neck, external sphincter, or rectum
T4b	Invades muscles and/or pelvic wall

Regional Lymph Nodes (N)

NX	Nodes cannot be assessed
N0	No regional node metastasis
N1	Single node metastasis, 2 centimeters (cm) or less at largest point
N2	Single node metastasis, 2 cm to 5 cm at largest point, or multiple nodes, no larger than 5 cm at largest point
N3	Metastasis larger than 5 cm in any node

Distant Metastasis (M)

MX	Metastasis cannot be assessed
M0	No distant metastasis
M1	Distant metastasis
M1a	Distant lymph node(s) involved
M1b	Bone(s) involved
M1c	Other site(s) involved

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Treatment for prostate cancer depends on the stage of the disease and the patient's age and overall health. Elderly patients with minor symptoms, early stage cancer, or coexisting illness may be treated conservatively.

Watchful waiting is a reasonable course of action for patients who are elderly, in poor health, or with early stage cancer. Untreated prostate cancer may take years to become problematic. During this time, the physician monitors the patient's condition for any marked or sudden progression of the disease, which may signal the need for more aggressive treatment.

Hormone Therapy

Hormone therapy for prostate cancer involves the use of antiandrogens to block production of testosterone, which prostate cancer cells use to grow. Drugs used for hormone therapy include leuprolid acetate (Viadur®), goserelin acetate implant (Zoladex®), bicalutamide (Casodex®), and flutamide (Eulexin®).

Viadur® is a matchstick-sized titanium pump inserted under the skin on the upper arm that delivers a constant rate of leuprolide acetate for 1 year. This prostate cancer treatment suppresses androgen (e.g., testosterone, estrogen) production, causing the tumor to shrink or stop growing and reducing symptoms (e.g., pain, urinary retention, urinary frequency).

A tablet located in one end of the implant draws moisture from surrounding tissue in the arm. The moisture exerts pressure within the device that steadily pushes medication from the other end.

The device is inserted under local anesthesia through a small incision. The incision must be kept dry for 24 hours and must remain bandaged for a few days. Strenuous physical activity should be avoided for 48 hours. The implant is removed after 12 months and a new device may be inserted.

Side effects associated with hormone therapy include the following:

• Depression
• Gynecomastia (enlargement of breast tissue)
• Headache
• Hematuria (blood in the urine)
• Hot flashes
• Lack of energy
• Local reaction to insertion (e.g., bruising, burning, itching)
• Ureteral or bladder outlet obstruction

Patients may also experience an increase in prostate cancer symptoms for approximately 2 weeks, due to a temporary increase in testosterone levels. Patients with advanced disease (e.g., large bone, bladder, or spinal cord tumors) may be unable to tolerate this increase in testosterone. Studies have shown that abarelix injection (Plenaxis™), which does not cause a surge in testosterone, can be used in some of these patients to relieve symptoms (e.g., bone pain, inability to urinate).

Plenaxis may cause life-threatening conditions in some people, such as a drop in blood pressure; loss of consciousness; breathing problems (e.g., shortness of breath, wheezing); and swelling of the face, eyelids, tongue, or throat. Patients must be monitored by a physician for at least 30 minutes after each administration of the drug in case an adverse reaction does occur.

Treatment involves one injection into the buttocks every 2 weeks for the first month, and every 4 weeks thereafter. Blood tests are performed every 2 months to monitor the effectiveness of the drug.

Common side effects include the following:

• Abnormal breast enlargement (gynecomastia), breast tenderness and pain
• Back pain
• Constipation
• Dizziness
• Fatigue
• Headache
• Hot flashes
• Increased urination
• Sleep disturbances
• Swelling of the legs and ankles (peripheral edema)

Treatment for Bone Metastases

Zoledronic acid (Zometa®) is a bisphosphonate prescribed to treat hypercalcemia—excess calcium in the blood—in prostate cancer patients who have bone metastases (secondary tumors in bone). Patients with hypercalcemia experience dehydration, fatigue, nausea, vomiting, confusion, and if untreated, may result in coma.

Bone metastases cause bone tissue to break down, which releases calcium into the bloodstream. Zoledronic acid increases bone density, decreases bone loss, and reduces the risk for fractures.

Patients must have completed at least one course of hormone therapy before starting this treatment. Doses are given intravenously for 15 minutes, every 3 to 4 weeks. A blood sample is taken before each treatment to monitor kidney function.

Zoledronic acid is not recommended for patients with severe kidney disease and should be used with caution in those with aspirin-sensitive asthma and those taking loop diuretics (e.g., hydrochlorothiazide).

Side effects usually are mild and temporary. Patients may experience the following:

• Anemia
• Constipation or diarrhea
• Fatigue
• Insomnia
• Joint, muscle, or bone pain
• Nausea
• Shortness of breath (dyspnea)
• Vomiting

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Two types of radiation therapy are used to treat prostate cancer: brachytherapy and external radiation therapy (XRT).

Brachytherapy

This treatment involves implanting tiny, radioactive capsules (called "seeds") into the cancerous prostate gland. The seeds emit radiation that kills the malignant tumor. Men with small tumors confined to the prostate (stage T1 or T2) are candidates for brachytherapy.

Transrectal ultrasound (TRUS) is used to create a three-dimensional grid map of the prostate, and a computer calculates the volume of the gland, the number of seeds needed, and determines where they will be placed.

The procedure is performed on an outpatient basis and takes 45 to 60 minutes. The patient is given regional anesthesia. A needle is inserted through the perineum and into the predetermined site(s). Fifty to 100 rice-sized seeds are implanted into the prostate through the needle. The seeds contain a radioactive isotope (usually palladium 103 or iodine 125) that emits radiation for about 3 months and then becomes inert.

Recovery
Brachytherapy patients are discharged the same day and usually resume routine activity within a day or so. In a recent study of 111 brachytherapy patients, 100% were free of prostate cancer 5 years after treatment.

Complications
A small number of patients, generally those over age 70, experience incontinence or impotence.

External Radiation Treatment (XRT)

XRT is recommended when the tumor has spread through the prostate capsule to surrounding tissues. XRT usually is given on an outpatient basis for 7 to 8 weeks. High-energy x-rays are projected onto prostate tissue from a machine outside the body. The radiation destroys cancer cells and shrinks tumors.

A study of 999 patients found 79% of stage T1, 66% of stage T2, 55% of stage T3, and 22% of stage T4 prostate cancer patients survived 10 years after XRT.

Complications
Impotence (particularly in older men), discomfort with urination, urinary urgency, and diarrhea (especially during the late stages of treatment) are commonly experienced with XRT.

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Surgery

Good candidates for surgery to treat prostate cancer have one or more of the following characteristics:

• Good health
• No spread of cancer to bone
• Tumor confined to the prostate gland (stage T1 and T2)
• Under the age of 70
• Expected to live another 10 years or longer

Depending on the extent of the disease, there are several surgical options for prostate cancer.

Cryosurgery

This minimally invasive outpatient procedure, also called cryoablation, destroys cancer cells by twice rapidly freezing and thawing cancerous tissue. It is recommended for patients who

• cannot tolerate surgery or radiation,
• have prostate-confined tumors (stage T3 or lower),
• do not respond to radiation (both external-beam and brachytherapy), and
• are elderly.

Transrectal ultrasound and prostate biopsy are performed prior to cryosurgery to determine the exact size and location of the tumor(s). The procedure is performed under regional (epidural nerve block) or general anesthesia.

With the man on his back, the surgeon inserts a warming catheter into the urethra to protect it from freezing temperatures. An ultrasound transducer is inserted into the rectum, so the surgeon can see the prostate and surrounding tissue and monitor placement of the cryoprobes. The surgeon then makes 5 to 8 needle punctures in the perineum and advances the needles to preselected locations in the prostate tumor. Liquid nitrogen or argon gas circulates through the probes and freezes cancer cells to —40°C.

The temperature in and around the prostate is monitored with thermosensors, also inserted through the perineum. Once the spheres of tissue surrounding the cryoprobes are covered with ice, the liquid nitrogen or argon circulation is stopped and the area is allowed to thaw. The freeze-thaw cycle is repeated and then the instruments are removed. The procedure takes about 2 hours.

Recovery
Patients usually go home the same day or the day after the procedure. A catheter is necessary for about 3 weeks. Most patients report very little discomfort and often recover fully within days.

Recent studies show that 97% of cryosurgery patients are cancer free at 1 year and 82% are cancer free at 5 years following surgery. Cryosurgery usually can be repeated safely if cancer returns.

Complications
The urethral warming device causes incontinence or urethral obstruction in about 1% of patients. There is an 85% chance that freezing will result in nerve damage and cause impotence. However, nerve-sparing techniques are being developed to help reduce that risk.

Radical Prostatectomy

Radical prostatectomy is the surgical removal of the prostate gland and surrounding tissues, including the seminal vesicles and the pelvic lymph nodes. Surgeons use one of two surgical techniques, retropubic prostatectomy or perineal prostatectomy. General anesthesia is used in both procedures.

In retropubic prostatectomy, an incision is made in the lower abdomen. This gives the surgeon access to the prostate gland, seminal vesicles, and the pelvic lymph nodes. In perineal prostatectomy, the incision is made in the perineum, the space between the scrotum and the rectum. With perineal prostatectomy, a second procedure is required to remove the pelvic lymph nodes (lymphadenectomy).

Recovery
ypically, patients remain in the hospital for 3 to 7 days after surgery and are catheterized for 2 to 3 weeks.

The 10-year survival rate after radical prostatectomy ranges from 75% to 97% for patients with well and moderately differentiated cancers (containing normal-appearing and slightly abnormal cells) and 60% to 86% for patients with poorly differentiated cancers (containing very abnormal cells).

Complications
Urinary leakage (incontinence) is common after surgery, but most men eventually regain urinary control. Surgeons try to avoid removing or cutting the nerves that control the ability to achieve an erection. Depending on the patient's age and the stage of the tumor, these nerve-sparing techniques enable about 40% to 65% of men who were sexually potent before surgery to remain so. There is also a risk for blood clots, which can cause heart failure. Radiation therapy may be recommended if cancer returns.

Laparoscopic Radical Prostatectomy

Laparoscopic radical prostatectomy is performed through several small incisions. A laparoscope (device consisting of a tube and an optical system) is inserted into one incision and is used to guide the procedure. Surgical instruments are inserted through the other incisions.

Laparoscopic radical prostatectomy causes less bleeding and less postoperative pain and results in a shorter hospital stay and recovery period. Catheterization is required for approximately 3 days following the procedure.

Lymphadenectomy

Prostate cancer usually spreads first to the lymph nodes in the pelvis. The physician assesses the likelihood of spread based on the biopsy results, PSA tests, and the size of the tumor. Lymphadenectomy is the surgical removal of lymph nodes. There are two types of lymphadenectomy, open and laparoscopic. General anesthesia is used in both procedures.

In an open lymphadenectomy, the lymph nodes are removed through an incision in the lower abdomen. Laparoscopic lymphadenectomy is performed with a laparoscope, a miniature telescopic device connected to a monitor. The laparoscope and other microinstruments are inserted through four small incisions in the lower abdomen. This procedure allows the patient to recover more quickly than open lymphadenectomy.

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