Prostate Cancer

Prostate Cancer

According to the American Cancer Society (ACS), prostate cancer is the most common type of cancer in men in the United States, other than skin cancer. Prostate cancer is the second leading cause of cancer death in men, exceeded only by lung cancer. Adenocarcinoma of the prostate is the clinical term for a cancerous tumor of the prostate gland. As prostate cancer grows, it may spread to the interior of the gland, to tissues near the prostate, to sac-like structures attached to the prostate (seminal vesicles), and to distant parts of the body (e.g., bones, liver, lungs). Prostate cancer confined to the gland often is treated successfully.

Risk Factors

When you’re told you have prostate cancer, it’s natural to wonder what may have caused the disease. But no one knows the exact causes of prostate cancer. Doctors seldom know why one man develops prostate cancer and another doesn’t. However, research has shown that men with certain risk factors are more likely than others to develop prostate cancer. A risk factor is something that may increase the chance of getting a disease. Studies have found the following risk factors for prostate cancer: Age over 65: Age is the main risk factor for prostate cancer. The chance of getting prostate cancer increases as you get older. In the United States, most men with prostate cancer are over 65. This disease is rare in men under 45. Family history: Your risk is higher if your father, brother, or son had prostate cancer. Race: Prostate cancer is more common among black men than white or Hispanic/Latino men. It’s less common among Asian/Pacific Islander and American Indian/Alaska Native men. Certain genome changes: Researchers have found specific regions on certain chromosomes that are linked to the risk of prostate cancer. According to recent studies, if a man has a genetic change in one or more of these regions, the risk of prostate cancer may be increased. The risk increases with the number of genetic changes that are found. Also, other studies have shown an elevated risk of prostate cancer among men with changes in certain genes, such as BRCA1 and BRCA2. Having a risk factor doesn’t mean that a man will develop prostate cancer. Most men who have risk factors never develop the disease. Many other possible risk factors are under study. For example, researchers have studied whether vasectomy (surgery to cut or tie off the tubes that carry sperm out of the testicles) may pose a risk, but most studies have found no increased risk. Also, most studies have shown that the chance of getting prostate cancer is not increased by tobacco or alcohol use, BPH, a sexually transmitted disease, obesity, a lack of exercise, or a diet high in animal fat or meat. Researchers continue to study these and other possible risk factors.

Prevention

Folate A 10-year study showed that prostate cancer risk was lower in men who had enough folate in their diets. Finasteride and Dutasteride Finasteride and dutasteride are medications typically used to treat benign enlargement of the prostate (BPH). These drugs block the enzyme that changes testosterone into dihydrotestosterone (DHT). Higher than normal levels of DHT may play a part in developing prostate cancer. Taking finasteride or dutasteride has been shown to lower the risk for prostate cancer, but it is not known if these drugs lower the risk of death from prostate cancer. The Prostate Cancer Prevention Trial (PCPT) studied whether the drug finasteride can prevent prostate cancer in men older than 55 years of age. This prevention study showed that prostate cancer was diagnosed less often in men who took finasteride compared to men who did not take the medicine. However, the number of deaths from prostate cancer was the same in both groups. Finasteride did have side effects, including erectile dysfunction, loss of desire for sex, and breast enlargement. The Reduction by Dutasteride of Prostate Cancer Events Trial (REDUCE) studied whether the drug dutasteride could prevent prostate cancer in men aged 50 to 75 years who were at a higher risk for the disease. This prevention study showed that men who took dutasteride were less likely to be diagnosed with prostate cancer compared to men who did not take it. Dutasteride also caused side effects, including erectile dysfunction and loss of desire for sex. The following have been proven NOT to affect the risk of prostate cancer, or their effects on prostate cancer risk are not known: Selenium and vitamin E The Selenium and Vitamin E Cancer Prevention Trial (SELECT) studied whether taking vitamin E and selenium (a mineral) will prevent prostate cancer. The selenium and vitamin E were taken as supplements by healthy men 55 years of age and older (50 years of age and older for African-American men). The study showed that selenium and vitamin E did not decrease the risk of prostate cancer. Diet It is not known if a low fat diet or increasing fruits and vegetables in the diet helps to decrease the risk of prostate cancer or death from prostate cancer. There are other health benefits from a healthy diet (i.e. lower cholesterol, less heart disease, etc.) Multivitamins Regular use of multivitamins has not been proven to increase the risk of localized prostate cancer. Lycopene One natural source of lycopene is tomatoes. There have been mixed results on studies regarding lycopene. Some studies have shown that a diet high in lycopene decreased the risk of developing prostate cancer, but other studies have not. It has not been proven that taking lycopene supplements decreases the risk of prostate cancer.

Symptoms of Prostate Cancer

A man with prostate cancer may not have any symptoms. Symptoms of prostate cancer are often similar to those of Benign Prostatic Hyperplasia/Enlarged Prostate (BPH). Men observing the following signs and/or symptoms should see their physician for a thorough examination:
Urinary problems – Not being able to pass urine, Having a hard time starting or stopping the urine flow
Needing to urinate often, especially at night
Weak flow of urine
Urine flow that starts and stops
Pain or burning during urination
Difficulty having an erection
Blood in the urine or semen
Frequent pain in the lower back, hips, or upper thighs If you have any of these symptoms, you should tell your doctor so that problems can be diagnosed and treated.

Detection of Prostate CancerYour doctor can check for prostate cancer before you have any symptoms. During an office visit, your doctor will ask about your personal and family medical history. You’ll have a physical exam. You may also have one or both of the following tests:

Digital rectal exam: Your doctor inserts a lubricated, gloved finger into the rectum and feels your prostate through the rectal wall. Your prostate is checked for hard or lumpy areas.
Blood test for prostate-specific antigen (PSA): A lab checks the level of PSA in your blood sample.
The prostate makes PSA. A high PSA level is commonly caused by BPH or prostatitis (inflammation of the prostate). Prostate cancer may also cause a high PSA level. The digital rectal exam and PSA test can detect a problem in the prostate. However, they can’t show whether the problem is cancer or a less serious condition. If you have abnormal test results, your doctor may suggest other tests to make a diagnosis. All, or none, of these tests may be ordered by your doctor: Free PSA: In the bloodstream, some of the PSA is bound to proteins and some is not. The percent of PSA that is not bound to proteins (free PSA) may help to determine if an abnormal PSA is more likely to be elevated due to benign enlargement of the prostate (BPH) or due to cancer. PCA3 Plus: PCA3 is a gene that is overexpressed in prostate cancer cells. After an attentive prostate exam, a urine sample is obtained. Cells in the urine are checked for levels of PCA3. This is test is used more frequently when people have had a negative biopsy previously.
Transrectal ultrasound: The doctor inserts a probe into the rectum to check your prostate for abnormal areas. It also measures the size of the prostate, which can help to determine if the PSA level is elevated for the size of the prostate. The probe sends out sound waves that people cannot hear (ultrasound). The waves bounce off the prostate. A computer uses the echoes to create a picture called a sonogram.
Transrectal biopsy: A biopsy is the removal of tissue to look for cancer cells. It’s the only sure way to diagnose prostate cancer. The doctor inserts needles through the rectum into the prostate. The doctor removes small tissue samples (called cores) from many areas of the prostate. Transrectal ultrasound is usually used to guide the insertion of the needles. A pathologist checks the tissue samples for cancer cells.

Diagnosis of Prostate Cancer

If cancer cells are found, the pathologist studies tissue samples from the prostate under a microscope to report the grade of the tumor. The grade tells how much the tumor tissue differs from normal prostate tissue. It suggests how fast the tumor is likely to grow. Tumors with higher grades tend to grow faster than those with lower grades. They are also more likely to spread. Doctors use tumor grade along with your age and other factors to suggest treatment options. The most commonly used system for grading is the Gleason score. Gleason scores range from 2 to 10. To come up with the Gleason score, the pathologist uses a microscope to look at the patterns of cells in the prostate tissue. The most common pattern is given a grade of 1 (most like normal cells) to 5 (most abnormal). If there is a second most common pattern, the pathologist gives it a grade of 1 to 5, and adds the two most common grades together to make the Gleason score. If only one pattern is seen, the pathologist counts it twice. For example, 4 + 3 = 7. This means that the most commonly seen grade of tumor cells seen is a 4 and the second most commonly seen tumor cells is a 3. Together a Gleason score of 7 is obtained. A high Gleason score (such as 10) means a high-grade prostate tumor. High-grade tumors are more likely than low-grade tumors to grow quickly and spread.

Staging of Prostate Cancer

If the biopsy shows that you have cancer, your doctor needs to learn the extent (stage) of the disease to help you choose the best treatment. Staging is a careful attempt to find out whether the tumor has invaded nearby tissues, whether the cancer has spread and, if so, to what parts of the body. Some men may need tests that make pictures of the body:
Bone scan: The doctor injects a small amount of a radioactive substance into a blood vessel. It travels through the bloodstream and collects in the bones. A machine called a scanner detects and measures the radiation. The scanner makes pictures of the bones on a computer screen or on film. The pictures may show cancer that has spread to the bones. Many times a plain x-ray is taken to help evaluate an abnormality seen on a bone scan.
CT scan: An x-ray machine linked to a computer takes a series of detailed pictures of your pelvis or other parts of the body. Doctors use CT scans to look for prostate cancer that has spread to lymph nodes and other areas. You may receive contrast material by injection into a blood vessel in your arm or hand, or by enema. The contrast material makes abnormal areas easier to see.
MRI: A strong magnet linked to a computer is used to make detailed pictures of areas inside your body. The doctor can view these pictures on a monitor and can print them on film. An MRI can show whether cancer has spread to lymph nodes or other areas.
Sometimes contrast material makes abnormal areas show up more clearly on the picture. Other times, a “coil” is placed into the rectum to help give more detailed pictures of the prostate. When prostate cancer spreads, it’s often found in nearby lymph nodes. If cancer has reached these nodes, it also may have spread to other lymph nodes, the bones, or other organs. When cancer spreads from its original place to another part of the body, the new tumor has the same kind of abnormal cells and the same name as the primary tumor. For example, if prostate cancer spreads to bones, the cancer cells in the bones are actually prostate cancer cells. The disease is metastatic prostate cancer, not bone cancer. For that reason, it’s treated as prostate cancer, not bone cancer. Doctors call the new tumor “distant” or metastatic disease. These are different stages of prostate cancer. The stage is determined by assessing the tumor itself as well as the status of the lymph nodes and other sites of spread of disease (metastasis). TNM Staging Evaluation of the (primary) tumor (‘T’) TX: cannot evaluate the primary tumor T0: no evidence of tumor T1: tumor present, but not detectable clinically or with imaging T1a: tumor was incidentally found in less than 5% of prostate tissue resected (for other reasons, i.e. BPH) T1b: tumor was incidentally found in greater than 5% of prostate tissue resected (for other reasons, i.e. BPH) T1c: tumor was found in a needle biopsy performed due to an elevated serum PSA T2: the tumor can be felt (palpated) on examination, but has not spread outside the prostate T2a: the tumor is in half or less than half of one of the prostate gland’s two lobes T2b: the tumor is in more than half of one lobe, but not both T2c: the tumor is in both lobes T3: the tumor has spread through the prostatic capsule (if it is only part-way through, it is still T2) T3a: the tumor has spread through the capsule on one or both sides T3b: the tumor has invaded one or both seminal vesicles T4: the tumor has invaded other nearby structures It should be stressed that the designation “T2c” implies a tumor which is palpable in both lobes of the prostate. Tumors which are found to be bilateral on biopsy only but which are not palpable bilaterally should not be staged as T2c. Evaluation of the regional lymph nodes (‘N’) NX: cannot evaluate the regional lymph nodes N0: there has been no spread to the regional lymph nodes N1: there has been spread to the regional lymph nodes Evaluation of distant metastasis (‘M’) MX: cannot evaluate distant metastasis M0: there is no distant metastasis M1: there is distant metastasis M1a: the cancer has spread to lymph nodes beyond the regional ones M1b: the cancer has spread to bone M1c: the cancer has spread to other sites (regardless of bone involvement) Overall Staging The tumor, lymph node, and metastasis status can be combined into four stages of worsening severity. Stage Tumor Nodes Metastasis Stage I T1a N0 M0 Stage II T1a N0 M0 T1b N0 M0 T1c N0 M0 T1 N0 M0 T2 N0 M0 Stage III T3 N0 M0 Stage IV T4 N0 M0 Any T N1 M0 Any T Any N M1 To explain this in further detail:
Stage I: o The cancer can’t be felt during a digital rectal exam, and it can’t be seen on an imaging study, such as ultrasound. It’s found by chance when surgery is done for another reason, usually for BPH. The cancer is only in the prostate and is very low grade (low Gleason score)
Stage II: o The tumor is more advanced or a higher grade than Stage I, but the tumor doesn’t extend beyond the prostate. It may be felt during a digital rectal exam, or it may be seen on a sonogram. It is detected either after a needle biopsy or surgery done for other reasons, i.e. resection of the prostate for benign enlargement.
Stage III: o The tumor extends beyond the capsule (outer covering) of the prostate. The tumor may have invaded the seminal vesicles, but cancer cells haven’t spread to the lymph nodes, bones or other organs.
Stage IV: o The tumor may have invaded the bladder, rectum, or nearby structures (beyond the seminal vesicles). It may have spread to the lymph nodes, bones, or to other parts of the body.

Treatment of Prostate Cancer

Men with prostate cancer have many treatment options. The treatment that’s best for one man may not be best for another. Your doctor will make recommendations that are best for each individual. The options include active surveillance (also called watchful waiting), surgery, radiation therapy, cryotherapy, hormone therapy, and chemotherapy. You may have a combination of treatments. The treatment that’s right for you depends mainly on your age, the grade of the tumor (the Gleason score), the number of biopsy tissue samples that contain cancer cells, the stage of the cancer, your symptoms, and your general health. Your doctor can describe your treatment choices, the expected results of each, and the possible side effects. You and your doctor can work together to develop a treatment plan that meets your medical and personal needs.

Active Surveillance

You may choose active surveillance if the risks and possible side effects of treatment outweigh the possible benefits. Your doctor may suggest active surveillance if you’re diagnosed with early stage prostate cancer that seems to be slowly growing. Your doctor may also offer this option if you are older or have other serious health problems. Choosing active surveillance doesn’t mean you’re giving up. It means you’re putting off the side effects of surgery or radiation therapy. Having surgery or radiation therapy is no guarantee that a man will live longer than a man who chooses to put off treatment. If you and your doctor agree that active surveillance is a good idea, your doctor will check you regularly (such as every 3 to 6 months, at first). After about one year, your doctor may order another biopsy to check the Gleason score. You may begin treatment if your Gleason score rises, your PSA level starts to rise, or you develop symptoms. You’ll receive surgery, radiation therapy, or another approach at that time. Active surveillance avoids or delays the side effects of surgery and radiation therapy, but this choice has risks. For some men, it may reduce the chance to control cancer before it spreads. Also, it may be harder to cope with surgery or radiation therapy when you’re older. If you choose active surveillance but grow concerned later, you should discuss your feelings with your doctor. Another approach is an option for most men.

Surgery

Surgery is an option for men with early (Stage I or II) prostate cancer. It’s sometimes an option for men with Stage III or IV prostate cancer. Before the surgeon removes the prostate, the lymph nodes in the pelvis may be removed. If prostate cancer cells are found in the lymph nodes, the disease may have spread to other parts of the body. If cancer has spread to the lymph nodes, the surgeon does not always remove the prostate and may suggest other types of treatment. After removing the prostate, the bladder is reconnected to the urethra (tube that men urinate through). Once healed, this will allow men to urinate normally. There are several types of surgery for prostate cancer. Each type has benefits and risks. You and your doctor can talk about the types of surgery and which may be right for you:
Robotic laparoscopic surgery: The surgeon removes the entire prostate through small cuts. A laparoscope and a robot are used to help remove the prostate. Instruments are passed through the small cuts and are used to remove the prostate. The surgeon uses handles below a computer display to control the robot’s arms.
Open surgery: The surgeon makes a large incision (cut) into your body to remove the tumor. There are two approaches:
Through the abdomen: The surgeon removes the entire prostate through a cut in the abdomen. The incision typically is from the umbilicus (belly button) down to the pelvic bone. This is called a radical retropubic prostatectomy.
Between the scrotum and anus: The surgeon removes the entire prostate through a cut between the scrotum and the anus. This is called a radical perineal prostatectomy.
Laparoscopic prostatectomy: The surgeon removes the entire prostate through small cuts, rather than a single long cut in the abdomen. A thin, lighted tube (a laparoscope) helps the surgeon see. Other instruments are passed through the small cuts. These instruments are used to remove the prostate.
Cryosurgery: For some men, cryosurgery is an option. The surgeon inserts a tool through a small cut between the scrotum and anus. The tool freezes and kills prostate tissue. Cryosurgery may also be used if the cancer returns following radiation therapy.
TURP: A man with advanced prostate cancer may choose TURP (transurethral resection of the prostate) to relieve symptoms. The surgeon inserts a long, thin scope through the urethra. A cutting tool at the end of the scope removes tissue from the inside of the prostate. TURP may not remove all of the cancer, but it can remove tissue that blocks the flow of urine.
After surgery, a catheter (flexible tube) is often left through the penis into the bladder. This allows the area to heal where the bladder and urethra are reconnected. Oftentimes patients only have to stay in the hospital overnight and can go home the following day. With newer surgical techniques, the complications from surgery are significantly reduced.

Radiation Therapy

Radiation therapy is an option for men with any stage of prostate cancer. Men with early stage prostate cancer may choose radiation therapy instead of surgery. It also may be used after surgery to destroy any cancer cells that remain in the area. It also may be used if the cancer recurs after surgery. In later stages of prostate cancer, radiation treatment may be used to help relieve pain. Radiation therapy (also called radiotherapy) uses high-energy rays to kill cancer cells. It affects cells only in the treated area. Doctors use two types of radiation therapy to treat prostate cancer. Some men receive both types:
External radiation: The radiation comes from a large machine outside the body. You will go to a hospital or clinic for treatment. Treatments are usually 5 days a week for several weeks. Many men receive 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy (IMRT). These types of treatment use computers to more closely target the cancer to lessen the damage to healthy tissue near the prostate.
Internal radiation (implant radiation or brachytherapy): The radiation comes from radioactive material usually contained in very small implants called seeds. Dozens of seeds are placed inside needles, and the needles are inserted into the prostate. The needles are removed, leaving the seeds behind. The seeds give off radiation for months. They don’t need to be removed once the radiation is gone. Radiation can also be delivered directly into the prostate without leaving radioactive seeds behind. Side effects depend mainly on the dose and type of radiation. You’re likely to be very tired during radiation therapy, especially in the later weeks of treatment. Resting is important, but doctors usually advise patients to try to stay active, unless it leads to pain or other problems. If you have external radiation, you may have diarrhea or frequent and uncomfortable urination. Some men have lasting bowel or urinary problems. Your skin in the treated area may become red, dry, and tender. You may lose hair in the treated area. The hair may not grow back. Internal radiation therapy may cause incontinence. This side effect usually goes away. Both internal and external radiation can cause impotence. You can talk with your doctor about ways to help cope with this side effect.

Hormone Therapy

A man with prostate cancer may have hormone therapy before, during, or after radiation therapy. Hormone therapy is also used alone for prostate cancer that has returned after treatment. Male hormones (androgens) can cause prostate cancer to grow. Hormone therapy keeps prostate cancer cells from getting the male hormones they need to grow. The testicles are the body’s main source of the male hormone testosterone. The adrenal gland makes other male hormones and a small amount of testosterone. Hormone therapy uses drugs or surgery:
Drugs: Your doctor may suggest a drug that can block natural hormones:
Luteinizing hormone-releasing hormone (LH-RH) agonists: These drugs can prevent the testicles from making testosterone. Examples are leuprolide, goserelin, and triptorelin. The testosterone level falls slowly. Without testosterone, the tumor shrinks, or its growth slows. These drugs are also called gonadotropin-releasing hormone (GnRH) agonists.
Antiandrogens: These drugs can block the action of male hormones. Examples are flutamide, bicalutamide, and nilutamide.
Other drugs: Some drugs can prevent the adrenal gland from making testosterone. Examples are ketoconazole and aminoglutethimide.
Surgery: Surgery to remove the testicles is called orchiectomy. After orchiectomy or treatment with an LH-RH agonist, your body no longer gets testosterone from the testicles, the major source of male hormones.
Because the adrenal gland makes small amounts of male hormones, you may receive an antiandrogen to block the action of the male hormones that remain. This combination of treatments is known as total androgen blockade (also called combined androgen blockade). Hormone therapy may cause side effects such as impotence, hot flashes, weight gain, fatigue, and loss of sexual desire. Also, any treatment that lowers hormone levels can weaken your bones. All patients receiving hormonal therapy should supplement their diet with calcium and vitamin D. Your doctor can suggest other medicines that may reduce your risk of bone fractures. An LH-RH agonist may make your symptoms worse for a short time at first. This temporary problem is called “flare.” To prevent flare, your doctor may give you an antiandrogen for a few weeks along with the LH-RH agonist. An LH-RH agonist such as leuprolide can increase body fat, especially around the waist. The levels of sugar and cholesterol in your blood may increase too. Because these changes increase the risk of diabetes and heart disease, your health care team will monitor you for these side effects. Antiandrogens (such as nilutamide) can cause nausea, diarrhea, or breast growth or tenderness. Rarely, they may cause liver problems (pain in the abdomen, yellow eyes, or dark urine). Some men who use nilutamide may have shortness of breath or develop heart failure. Some may have trouble adjusting to sudden changes in light. If you receive total androgen blockade, you may have more side effects than if you have just one type of hormone treatment. If used for a long time, ketoconazole may cause liver problems, and aminoglutethimide can cause skin rashes. Doctors usually treat prostate cancer that has spread to other parts of the body with hormone therapy. For some men, the cancer will be controlled for two or three years, but others will have a much shorter response to hormone therapy. In time, most prostate cancers can grow with very little or no male hormones, and hormone therapy alone is no longer helpful. At that time, your doctor may suggest chemotherapy or other forms of treatment that are under study. In many cases, the doctor may suggest continuing with hormone therapy because it may still be effective against some of the cancer cells.

Chemotherapy

Chemotherapy may be used for prostate cancer that has spread and no longer responds to hormone therapy. Chemotherapy uses drugs to kill cancer cells. The drugs for prostate cancer are usually given through a vein (intravenous). You may receive chemotherapy in a clinic, at the doctor’s office, or at home. Some men need to stay in the hospital during treatment. The side effects depend mainly on which drugs are given and how much. Chemotherapy kills fast-growing cancer cells, but the drugs can also harm normal cells that divide rapidly:
Blood cells: When chemotherapy lowers the levels of healthy blood cells, you’re more likely to get infections, bruise or bleed easily, and feel very weak and tired. Your health care team will check for low levels of blood cells. If your levels are low, your health care team may stop the chemotherapy for a while or reduce the dose of drug. There are also medicines that can help your body make new blood cells.
Cells in hair roots: Chemotherapy may cause hair loss. If you lose your hair, it will grow back, but it may change in color and texture.
Cells that line the digestive tract: Chemotherapy can cause a poor appetite, nausea and vomiting, or diarrhea.
Your health care team can give you medicines and suggest other ways to help with these problems. Other side effects include shortness of breath and a problem with your body holding extra water. Your health care team can give you medicine to protect against too much water building up in the body. Also, chemotherapy may cause a skin rash, tingling or numbness in your hands and feet, and watery eyes. Your health care team can suggest ways to control many of these problems. Most go away when treatment ends.

Immunotherapy

Immunotherapy is a treatment that stimulates the body’s own immune system to fight a disease. Provenge (sipuleucel-T) is a treatment that uses the bodies’ own immune system to attack prostate cancer cells. This treatment is used when hormonal therapy is no longer controlling the cancer. Provenge is a vaccine that has extended the lives of patients with metastatic prostate cancer. Side effects of the medication may include chills, fatigue, fever, back pain, nausea and headache.