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is a
Disease in which
Cancer develops in the
Prostate , a gland in the
Male Reproductive System . It occurs when
Cell s of the prostate
Mutate and begin to multiply out of control. These cells may spread (
Metastasize ) from the prostate to other parts of the body, especially the
Bone s and
Lymph Node s. Prostate cancer may cause pain, difficulty in
Urinating ,
Erectile Dysfunction and other
Symptom s.
Rates of prostate cancer vary widely across the world. Although the rates vary widely between countries, it is least common in South and East Asia, more common in Europe, and most common in the United States.
1 Retrieved on ). Retrieved on
2007-04-05 However, these high rates may be affected by increasing rates of detection.
2
Prostate cancer develops most frequently in men over fifty. This cancer can occur only in men, as the prostate is exclusively of the male reproductive tract. It is the most common type of cancer in men in the United States, where it is responsible for more male deaths than any other cancer, except
Lung Cancer . However, many men who develop prostate cancer never have symptoms, undergo no therapy, and eventually die of other causes. Many factors, including
Genetics and
Diet , have been implicated in the development of prostate cancer.
Prostate cancer is most often discovered by
Physical Examination or by screening
Blood Test s, such as the PSA (
Prostate Specific Antigen ) test. There is some current concern about the accuracy of the PSA test and its usefulness. Suspected prostate cancer is typically confirmed by removing a piece of the prostate (
Biopsy ) and examining it under a
Microscope . Further tests, such as
X-ray s and
Bone Scan s, may be performed to determine whether prostate cancer has spread.
Prostate cancer can be treated with
Surgery ,
Radiation Therapy ,
Hormonal Therapy , occasionally
Chemotherapy ,
Proton Therapy , or some combination of these. The age and underlying health of the man as well as the extent of spread, appearance under the microscope, and response of the cancer to initial treatment are important in determining the outcome of the disease. Since prostate cancer is a disease of older men, many will die of other causes before a slowly advancing prostate cancer can spread or cause symptoms. This makes treatment selection difficult.
3 The decision whether or not to treat localized prostate cancer (a tumor that is contained within the prostate) with curative intent is a
Patient Trade-off between the expected beneficial and harmful effects in terms of patient survival and quality of life.
See Also: Prostate
The
Prostate is a male
Reproductive Organ which helps make and store
Seminal Fluid . In adult men a typical prostate is about three centimeters long and weighs about twenty grams.
4 It is located in the
Pelvis , under the
Urinary Bladder and in front of the
Rectum . The prostate surrounds part of the
Urethra , the tube that carries
Urine from the bladder during
Urination and semen during
Ejaculation .
5 Because of its location, prostate diseases often affect urination, ejaculation, and rarely
Defecation . The prostate contains many small
Gland s which make about twenty percent of the fluid constituting semen.
6 In prostate cancer the cells of these prostate glands
Mutate into cancer cells. The prostate glands require male
Hormone s, known as
Androgen s, to work properly. Androgens include
Testosterone , which is made in the
Testes ;
Dehydroepiandrosterone , made in the
Adrenal Gland s; and
Dihydrotestosterone , which is converted from testosterone within the prostate itself. Androgens are also responsible for
Secondary Sex Characteristic s such as facial hair and increased muscle mass.
Early prostate cancer usually causes no symptoms. Often it is diagnosed during the workup for an elevated
PSA noticed during a routine checkup. Sometimes, however, prostate cancer does cause symptoms, often similar to those of diseases such as
Benign Prostatic Hypertrophy . These include
Frequent Urination ,
Increased Urination At Night , difficulty starting and maintaining a steady stream of urine,
Blood In The Urine , and painful urination. Prostate cancer may also cause problems with sexual function, such as difficulty achieving
Erection or painful
Ejaculation .
7
Advanced prostate cancer may cause additional symptoms as the disease spreads to other parts of the body. The most common symptom is
Bone Pain , often in the
Vertebrae (bones of the spine),
Pelvis or
Rib s, from cancer which has spread to these bones. Prostate cancer in the
Spine can also compress the
Spinal Cord , causing leg weakness and
Urinary and
Fecal Incontinence .
8
. Cancer cells avoid apoptosis and continue to multiply in an unregulated manner.]]
Prostate cancer is classified as an
Adenocarcinoma , or glandular cancer, that begins when normal semen-secreting prostate gland cells
Mutate into cancer cells. The region of prostate gland where the adenocarcinoma is most common is the peripheral zone. Initially, small clumps of cancer cells remain confined to otherwise normal prostate glands, a condition known as
Carcinoma In Situ or
Prostatic Intraepithelial Neoplasia (PIN). Although there is no proof that PIN is a cancer precursor, it is closely associated with cancer. Over time these cancer cells begin to multiply and spread to the surrounding prostate tissue (the
Stroma ) forming a
Tumor . Eventually, the tumor may grow large enough to invade nearby organs such as the
Seminal Vesicles or the
Rectum , or the tumor cells may develop the ability to travel in the
Blood stream and
Lymphatic System . Prostate cancer is considered a
Malignant tumor because it is a mass of cells which can invade other parts of the body. This invasion of other organs is called
Metastasis . Prostate cancer most commonly metastasizes to the
Bone s,
Lymph Node s, rectum, and bladder.
The specific causes of prostate cancer remain unknown.
9 A man's risk of developing prostate cancer is related to his
Age ,
Genetics ,
Race ,
Diet ,
Lifestyle ,
Medication s, and other factors. The primary risk factor is age. Prostate cancer is uncommon in men less than 45, but becomes more common with advancing age. The average age at the time of diagnosis is 70.
10 However, many men never know they have prostate cancer. Autopsy studies of Chinese, German, Israeli, Jamaican, Swedish, and Ugandan men who died of other causes have found prostate cancer in thirty percent of men in their 50s, and in eighty percent of men in their 70s.
11 In the year 2005 in the United States, there were an estimated 230,000 new cases of prostate cancer and 30,000 deaths due to prostate cancer.
12 Erratum in: CA Cancer J Clin. 2005 Jul-Aug;55(4):259
A man's genetic background contributes to his risk of developing prostate cancer. This is suggested by an increased
Incidence of prostate cancer found in certain racial groups, in identical
Twin s of men with prostate cancer, and in men with certain
Gene s. In the United States, prostate cancer more commonly affects black men than white or Hispanic men, and is also more deadly in black men.
13 Men who have a brother or father with prostate cancer have twice the usual risk of developing prostate cancer.
14 Studies Of Twins in
Scandinavia suggest that forty percent of prostate cancer risk can be explained by
Inherited Factors .
15 However, no single gene is responsible for prostate cancer; many different genes have been implicated. Two genes (''
BRCA1 '' and ''
BRCA2 '') that are important risk factors for
Ovarian Cancer and
Breast Cancer in women have also been implicated in prostate cancer.
16
Dietary amounts of certain (Vitamin E is found in
Green, Leafy Vegetables ),
Lycopene (found in tomatoes),
Omega-3 Fatty Acid s (found in fatty fishes like
Salmon ), and the mineral
Selenium . A study in 2007 cast doubt on the effectiveness of
Lycopene (found in tomatoes) in reducing the risk of prostate cancer.
18 Lower
Blood levels of
Vitamin D also may increase the risk of developing prostate cancer. This may be linked to lower exposure to
Ultraviolet (UV) Light , since UV light exposure can increase vitamin D in the body.
19
There are also some links between prostate cancer and medications, medical procedures, and medical conditions. Daily use of or
Inflammation of the prostate (
Prostatitis ) may increase the chance for prostate cancer. In particular, infection with the
Sexually Transmitted Infection s
Chlamydia ,
Gonorrhea , or
Syphilis seems to increase risk.
24
Finally,
Obesity 25
and elevated blood levels of
Testosterone 26
may increase the risk for prostate cancer.
Research released in May 2007, found that US war veterans who had been exposed to
Agent Orange had a 48% increased risk of prostate cancer recurrence following surgery.
27
Prostate cancer risk can be decreased by modifying known risk factors for prostate cancer, such as decreasing intake of animal fat.
28
One research study, by the that this could be because regular ejaculation reduces the buildup of
Carcinogenic deposits which could damage the cells lining the prostate. The researchers also speculated that frequent ejaculation may cause the prostate to mature fully, making it less susceptible to carcinogens. It is also possible that there is another factor (such as hormone levels) that is a
Common Cause of both a reduced susceptibility to prostate cancer and a tendency toward frequent masturbation.
There is also some evidence that frequent sexual intercourse is associated with reduced risk of protate cancer, although contrarily the risks associated with STDs have been shown to increase the risk of prostate cancerhttp://news.bbc.co.uk/1/hi/health/3072021.stm. Once the lining of the prostate is affected with cancer, the only known treatments are surgery and radiation therapy. Both may limit the ability to have erections afterward.
Several medications and vitamins may also help prevent prostate cancer. Two dietary supplements, drug
Toremifene has shown promise in early trials.
3031
Two medications which block the conversion of
Testosterone to
Dihydrotestosterone ,
Finasteride 32
and
Dutasteride ,
33 have also shown some promise.
As Of 2006 the use of these medications for primary prevention is still in the testing phase, and they are not widely used for this purpose. The problem with these medications is that they may preferentially block the development of lower-grade prostate tumors, leading to a relatively greater chance of higher grade cancers, and negating any overall survival improvement.
Green Tea may be protective (due to its
Polyphenol content), though the data is mixed.Lee AH, Fraser ML, Meng X, Binns CW. ''Protective effects of green tea against prostate cancer.'' Expert Rev Anticancer Ther. 2006 Apr;6(4):507-13. Review. PMID 16613539Kikuchi N, Ohmori K, Shimazu T, Nakaya N, Kuriyama S, Nishino Y, Tsubono Y, Tsuji I. ''No association between green tea and prostate cancer risk in Japanese men: the Ohsaki Cohort Study.'' Br J Cancer. 2006 August 7;95(3):371-3. Epub 2006 June 27. PMID 16804523
A 2006 study of green tea derivatives demonstrated promising prostate cancer prevention in patients at high risk for the disease.
34 In 2003, an Australian research team led by Graham Giles of The Cancer Council Australia concluded that frequent
Masturbation by males appears to help prevent the development of prostate cancer.http://news.bbc.co.uk/1/hi/health/3072021.stm
Recent research published in the Journal of the ,
Broccoli , or one of the other
Cruciferous Vegetables , more than once a week were 40% less likely to develop prostate cancer than men who rarely ate those vegetables.http://www.cbsnews.com/stories/2007/07/24/health/webmd/main3094509.shtml Scientists believe the reason for this phenomenon has to do with a phytochemical called Diindolylmethane in these vegetables that has anti-androgenic and immune modulating properties. This compound is currently under investigation by the National Cancer Institute as a natural therapeutic for prostate cancer.
See Also: Prostate cancer screening
Prostate cancer
Screening is an attempt to find unsuspected cancers. Screening tests may lead to more specific follow-up tests such as a
Biopsy , where small pieces of the prostate are removed for closer study.
As Of 2006 prostate cancer screening options include the
Digital Rectal Exam and the
Prostate Specific Antigen (PSA) blood test. Screening for prostate cancer is controversial because it is not clear if the benefits of screening outweigh the risks of follow-up diagnostic tests and cancer treatments.
Prostate cancer is a slow-growing cancer, very common among older men. In fact, most prostate cancers never grow to the point where they cause symptoms, and most men with prostate cancer die of other causes before prostate cancer has an impact on their lives. The PSA screening test may detect these small cancers that would never become life threatening. Doing the PSA test in these men may lead to
Overdiagnosis , including additional testing and treatment. Follow-up tests, such as
Prostate Biopsy , may cause pain, bleeding and infection. Prostate cancer treatments may cause urinary
Incontinence and
Erectile Dysfunction . Therefore, it is essential that the risks and benefits of diagnostic procedures and treatment be carefully considered before PSA screening.
Prostate cancer screening generally begins after age 50, but this can vary due to ethnic backgrounds. An example of this is males who have a strong family history of prostate cancer.
35 The American Academy of Family Physicians and American College of Physicians recommend the physician discuss the risks and benefits of screening and decide based on individual patient preference.
36 Although there is no officially recommended cutoff, many health care providers stop monitoring PSA in men who are older than 75 years old because of concern that prostate cancer therapy may do more harm than good as age progresses and life expectancy decreases.
Digital Rectal Examination (DRE) is a procedure where the examiner inserts a gloved, lubricated finger into the rectum to check the size, shape, and texture of the prostate. Areas which are irregular, hard or lumpy need further evaluation, since they may contain cancer. Although the DRE only evaluates the back of the prostate, 85% of prostate cancers arise in this part of the prostate. Prostate cancer which can be felt on DRE is generally more advanced.
37 The use of DRE has never been shown to prevent prostate cancer deaths when used as the only screening test.
38
See Also: Prostate specific antigen
The PSA test measures the blood level of
Prostate-specific Antigen , an
Enzyme produced by the prostate. Specifically, PSA is a
Serine Protease similar to
Kallikrein . Its normal function is to liquify gelatinous semen after ejaculation, allowing
Spermatazoa to more easily navigate through the uterine
Cervix .
PSA levels under 4 ng/mL (
Nanogram s per
Milliliter ) are generally considered normal, while levels over 4 ng/mL are considered abnormal (although in men over 65 levels up to 6.5 ng/mL may be acceptable, depending upon each laboratory's reference ranges). PSA levels between 4 and 10 ng/mL indicate a risk of prostate cancer higher than normal, but the risk does not seem to rise within this six-point range. When the PSA level is above 10 ng/mL, the association with cancer becomes stronger. However, PSA is not a perfect test. Some men with prostate cancer do not have an elevated PSA, and most men with an elevated PSA do not have prostate cancer.
PSA levels can change for many reasons other than cancer. Two common causes of high PSA levels are enlargement of the prostate (
Benign Prostatic Hypertrophy (BPH)) and infection in the prostate (
Prostatitis ). It can also be raised for 24 hours after ejaculation and several days after catheterization. PSA levels are lowered in men who use medications used to treat BPH or
Baldness . These medications,
Finasteride (marketed as Proscar or Propecia) and
Dutasteride (marketed as Avodart), may decrease the PSA levels by 50% or more.
Several other ways of evaluating the PSA have been developed to avoid the shortcomings of simple PSA screening. The use of age-specific reference ranges improves the sensitivity and specificity of the test. The rate of rise of the PSA over time, called the PSA velocity, has been used to evaluate men with PSA levels between 4 and 10 ng/ml, but
As Of 2006 , it has not proven to be an effective screening test.
39 Comparing the PSA level with the size of the prostate, as measured by
Ultrasound or
Magnetic Resonance Imaging , has also been studied. This comparison, called PSA density, is both costly and,
As Of 2006 , has not proven to be an effective screening test.
40 PSA in the blood may either be free or bound to other
Protein s. Measuring the amount of PSA which is free or bound may provide additional screening information, but
As Of 2006 , questions regarding the usefulness of these measurements limit their widespread use.
4142
When a man has symptoms of prostate cancer, or a screening test indicates an increased risk for cancer, more invasive evaluation is offered.
The only test which can fully confirm the diagnosis of prostate cancer is a
Biopsy , the removal of small pieces of the prostate for microscopic examination. However, prior to a biopsy, several other tools may be used to gather more information about the prostate and the urinary tract.
Cystoscopy shows the urinary tract from inside the bladder, using a thin, flexible camera tube inserted down the
Urethra .
Transrectal Ultrasonography creates a picture of the prostate using sound waves from a probe in the rectum.
See Also: Prostate biopsy
If cancer is suspected, a biopsy is offered. During a biopsy a
Urologist obtains tissue samples from the prostate via the rectum. A biopsy gun inserts and removes special hollow-core needles (usually three to six on each side of the prostate) in less than a second. Prostate biopsies are routinely done on an outpatient basis and rarely require hospitalization. Fifty-five percent of men report discomfort during prostate biopsy.
43
See Also: Gleason score
The tissue samples are then examined under a microscope to determine whether cancer cells are present, and to evaluate the microscopic features (or
Gleason Score ) of any cancer found.
See Also: Tumor markers
Tissue samples can be stained for the presence of PSA and other tumor markers in order to determine the origin of maligant cells that have metastasized.
44
Currently, an active area of research involves non-invasive methods of prostate tumor detection. Adenoviruses modified to transfect tumor cells with harmless yet distinct genes (such as luciferase) have proven capable of early detection. So far, though, this area of research has only been tested in animal and
LNCaP models.Iyer M, Salazar FB, Lewis X, Zhang L, Wu L, Carey M and Gambhir SS. Non-invasive imaging of a transgenic mouse model using a prostate-specific two-step transcriptional amplification strategy. Transg Res.2005; 14(1): 47–55
Another potential non-invasive methods of early prostate tumor detection is through a molecular test that detects the presence of cell-associated
PCA3 mRNA in urine.
PCA3 mRNA is expressed almost exclusively by prostate cells and has been shown to be highly over-expressed in prostate cancer cells.
It was reported in ,
2007 .
45
See Also: Prostate cancer staging
An important part of evaluating prostate cancer is determining the
Stage , or how far the cancer has spread. Knowing the stage helps define
Prognosis and is useful when selecting therapies. The most common system is the four-stage
TNM system (abbreviated from Tumor/Nodes/Metastases). Its components include the size of the tumor, the number of involved
Lymph Node s, and the presence of any other
Metastases .
The most important distinction made by any staging system is whether or not the cancer is still confined to the prostate. In the TNM system, clinical T1 and T2 cancers are found only in the prostate, while T3 and T4 cancers have spread elsewhere. Several tests can be used to look for evidence of spread. These include
Computed Tomography to evaluate spread within the pelvis,
Bone Scan s to look for spread to the bones, and
Endorectal Coil Magnetic Resonance Imaging to closely evaluate the prostatic capsule and the
Seminal Vesicles . Bone scans should reveal osteoblastic appearance due to ''increased'' bone density in the areas of bone metastisis - opposite to what is found in many other cancers that metastisize.
After a prostate biopsy, a
Pathologist looks at the samples under a microscope. If cancer is present, the pathologist reports the
Grade of the tumor. The grade tells how much the tumor tissue differs from normal prostate tissue and suggests how fast the tumor is likely to grow. The Gleason system is used to grade prostate tumors from 2 to 10, where a
Gleason Score of 10 indicates the most abnormalities. The pathologist assigns a number from 1 to 5 for the most common pattern observed under the microscope, then does the same for the second most common pattern. The sum of these two numbers is the Gleason score. The
Whitmore-Jewett Stage is another method sometimes used. Proper grading of the tumor is critical, since the grade of the tumor is one of the major factors used to determine the treatment recommendation.
Many prostate cancers are not destined to be lethal, and most men will ultimately die from causes other than of the disease. Decisions about treatment type and timing may therefore be informed by an estimation of the that the tumor will ultimately recur after treatment and/or progress to metastases and mortality. Several tools are available to help predict outcomes such as pathologic stage and recurrence after surgery or radiation therapy. Most combine stage, grade, and PSA level, and some also add the number or percent of biopsy cores positive, age, and/or other information.
The D’Amico classification stratifies men to low, intermediate, or high risk based on stage, grade, and PSA. It is used widely in clinical practice and research settings. The major downside to the 3-level system is that it does not account for multiple adverse parameters (e.g., high Gleason score ''and'' high PSA) in stratifying patients.
The Partin tables predict pathologic outcomes (margin status, extraprostatic extension, and seminal vesicle invasion) based on the same 3 variables, and are published as lookup tables.
The Kattan nomograms predict recurrence after surgery and/or radiation therapy, based on data available either at time of diagnosis or after surgery. The nomograms can be calculated using paper graphs, or using software available on a website or for handheld computers. The Kattan score represents the likelihood of remaining free of disease at a given time interval following treatment.
The
UCSF Cancer of the Prostate Risk Assessment (CAPRA) score predicts both pathologic status and recurrence after surgery. It offers comparable accuracy as the Kattan preoperative nomogram, and can be calculated without paper tables or a calculator. Points are assigned based on PSA, Grade, stage, age, and percent of cores positive; the sum yields a 0–10 score, with every 2 points representing roughly a doubling of risk of recurrence. The CAPRA score was derived from community-based data in the
CaPSURE database.
Treatment for prostate cancer may involve
Watchful Waiting ,
Surgery ,
Radiation Therapy ,
High Intensity Focused Ultrasound (HIFU) ,
Chemotherapy ,
Cryosurgery , hormonal therapy, or some combination. Which option is best depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors are the man's age, his general health, and his feelings about potential treatments and their possible side effects. Because all treatments can have significant
Side Effect s, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations.
The selection of treatment options may be a complex decision involving many factors. For example, radical prostatectomy after primary radiation failure is a very technically challenging surgery and may not be an option. www.nature.com/pcan/journal/v9/n1/full/4500853a.html This may enter into the treatment decision.
If the cancer has spread beyond the prostate, treatment options significantly change, so most doctors who treat prostate cancer use a variety of , hormonal therapy, and chemotherapy may also be offered if initial treatment fails and the cancer progresses.
Watchful Waiting , also called "active surveillance," refers to observation and regular monitoring without invasive treatment. Watchful waiting is often used when an early stage, slow-growing prostate cancer is found in an older man. Watchful waiting may also be suggested when the risks of surgery, radiation therapy, or hormonal therapy outweigh the possible benefits. Other treatments can be started if symptoms develop, or if there are signs that the cancer growth is accelerating (e.g., rapidly rising PSA, increase in Gleason score on repeat biopsy, etc.). Most men who choose watchful waiting for early stage tumors eventually have signs of tumor progression, and they may need to begin treatment within three years.
46 Although men who choose watchful waiting avoid the risks of surgery and radiation, the risk of metastasis (spread of the cancer) may be increased. For younger men, a trial of active surveillance may not mean avoiding treatment altogether, but may reasonably allow a delay of a few years or more, during which time the quality of life impact of active treatment can be avoided. Published data to date suggest that carefully selected men will not miss a window for cure with this approach. Additional health problems that develop with advancing age during the observation period can also make it harder to undergo surgery and radiation therapy.
Clinically insignificant prostate tumors are often found by accident when a doctor incorrectly orders a biopsy not following the recommended guidelines (abnormal DRE and elevated PSA). The urologist must check that the PSA is not elevated for other reasons, Prostatitis, etc. An annual biopsy is often recommended by a urologist for a patient who has selected watchful waiting when the tumor is clinically insignificant (no abnormal DRE or PSA). The tumors tiny size can be monitored this way and the patient can decide to have surgery only if the tumor enlarges which may take many years or never.
Surgical removal of the prostate, or
Prostatectomy , is a common treatment either for early stage prostate cancer, or for cancer which has failed to respond to radiation therapy. The most common type is
Radical Retropubic Prostatectomy , when the surgeon removes the prostate through an abdominal incision. Another type is
Radical Perineal Prostatectomy , when the surgeon removes the prostate through an incision in the
Perineum , the skin between the
Scrotum and
Anus . Radical prostatectomy can also be performed laparoscopically, through a series of small (1cm) incisions in the abdomen, with or without the assistance of a surgical robot.
Radical Prostatectomy is effective for tumors which have not spread beyond the prostate;
47 cure rates depend on risk factors such as PSA level and Gleason grade. However, it may cause
Nerve damage that significantly alters the quality of life of the prostate cancer survivor. The most common serious complications are loss of
Urinary Control and
Impotence . Reported rates of both complications vary widely depending on how they are assessed, by whom, and how long after surgery, as well as the setting (e.g., academic series vs. community-based or population-based data). Although penile sensation and the ability to achieve
Orgasm usually remain intact, erection and ejaculation are often impaired. Medications such as
Sildenafil (Viagra),
Tadalafil (Cialis), or
Vardenafil (Levitra) may restore some degree of potency. For most men with organ-confined disease, a more limited "nerve-sparing" technique may help avoid urinary incontinence and impotence.
48
Radical prostatectomy has traditionally been used alone when the cancer is small. In the event of positive margins or locally advanced disease found on pathology, adjuvant radiation therapy may offer improved survival. Surgery may also be offered when a cancer is not responding to radiation therapy. However, because radiation therapy causes tissue changes, prostatectomy after radiation has a higher risk of complications.
Transurethral Resection Of The Prostate , commonly called a "TURP," is a surgical procedure performed when the tube from the bladder to the penis (
Urethra ) is blocked by prostate enlargement. TURP is generally for benign disease and is not meant as definitive treatment for prostate cancer. During a TURP, a small tube (
Cystoscope ) is placed into the penis and the blocking prostate is cut away.
In metastatic disease, where cancer has spread beyond the prostate, removal of the
Testicle s (called
Orchiectomy ) may be done to decrease testosterone levels and control cancer growth. (See hormonal therapy, below).
''' for prostate cancer is administered using "seeds," small radioactive rods implanted directly into the tumor.]] and
Brachytherapy .
External beam radiation therapy uses a
Linear Accelerator to produce high-energy x-rays which are directed in a beam towards the prostate. A technique called Intensity Modulated Radiation Therapy (IMRT) may be used to adjust the radiation beam to conform with the shape of the tumor, allowing higher doses to be given to the prostate and seminal vesicles with less damage to the bladder and rectum. External beam radiation therapy is generally given over several weeks, with daily visits to a radiation therapy center. New types of radiation therapy may have fewer side effects then traditional treatment, one of these is
Tomotherapy .
for prostate cancer is delivered by a linear accelerator, such as this one.]]
Permanent implant brachytherapy is a popular treatment choice for patients with low to intermediate risk features, can be performed on an outpatient basis, and is associated with good 10-year outcomes with relatively low morbidity
49 Review. It involves the placement of about 100 small "seeds" containing radioactive material (such as
Iodine-125 or
Palladium-103 ) with a needle through the skin of the
Perineum directly into the tumor while under spinal or general anesthetic. These seeds emit
Lower-energy X-rays which are only able to travel a short distance. Although the seeds eventually become inert, they remain in the prostate permanently. The risk of exposure to others from men with implanted seeds is generally accepted to be insignificant.
50 Review.
Radiation therapy is commonly used in prostate cancer treatment. It may be used instead of surgery for early cancers, and it may also be used in advanced stages of prostate cancer to treat painful bone metastases. Radiation treatments also can be combined with hormonal therapy for intermediate risk disease, when radiation therapy alone is less likely to cure the cancer. Some radiation oncologists combine external beam radiation and brachytherapy for intermediate to high risk situations. One study found that the combination of six months of androgen suppressive therapy combined with external beam radiation had improved survival compared to radiation alone in patients with localized prostate cancer.
51 Others use a "triple modality" combination of external beam radiation therapy, brachytherapy, and hormonal therapy.
Less common applications for radiotherapy are when cancer is compressing the spinal cord, or sometimes after surgery, such as when cancer is found in the seminal vesicles, in the lymph nodes, outside the prostate capsule, or at the margins of the biopsy.
Radiation therapy is often offered to men whose medical problems make surgery more risky. Radiation therapy appears to cure small tumors that are confined to the prostate just about as well as surgery. However,
As Of 2006 some issues remain unresolved, such as whether radiation should be given to the rest of the pelvis, how much the
Absorbed Dose should be, and whether hormonal therapy should be given at the same time.
Side effects of radiation therapy might occur after a few weeks into treatment. Both types of radiation therapy may cause
Diarrhea and
Rectal Bleeding due to
Radiation Proctitis , as well as urinary incontinence and impotence. Symptoms tend to improve over time.
52 Men who have undergone external beam radiation therapy will have a higher risk of later developing
Colon Cancer and
Bladder Cancer .
53
Cryosurgery is another method of treating prostate cancer. It is less invasive than radical prostatectomy, and
General Anesthesia is less commonly used. Under ultrasound guidance, a method invented by Dr.
Gary Onik ,
54 metal rods are inserted through the skin of the
Perineum into the prostate. Highly purified Argon gas is used to cool the rods, freezing the surrounding tissue at −196 °
C (−320 °
F ). As the water within the prostate cells freeze, the cells die. The
Urethra is protected from freezing by a
Catheter filled with warm liquid. Cryosurgery generally causes fewer problems with urinary control than other treatments, but impotence occurs up to ninety percent of the time. When used as the initial treatment for prostate cancer and in the hands of an experienced cryosurgeon, cryosurgery has a 10 year biochemical disease free rate superior to all other treatments including radical prostatectomy and any form of radiation
55 Cryosurgery has also been demonstrated to be superior to radical prostatectomy for recurrent cancer following radiation therapy.
Hormonal Therapy uses medications or surgery to block prostate cancer cells from getting
Dihydrotestosterone (DHT), a hormone produced in the prostate and required for the growth and spread of most prostate cancer cells. Blocking DHT often causes prostate cancer to stop growing and even shrink. However, hormonal therapy rarely cures prostate cancer because cancers which initially respond to hormonal therapy typically become resistant after one to two years. Hormonal therapy is therefore usually used when cancer has spread from the prostate. It may also be given to certain men undergoing radiation therapy or surgery to help prevent return of their cancer.
56 Review.
Hormonal therapy for prostate cancer targets the pathways the body uses to produce DHT. A
Feedback Loop involving the testicles, the hypothalamus, and the pituitary, adrenal, and prostate glands controls the blood levels of DHT. First, low blood levels of DHT stimulate the
Hypothalamus to produce
Gonadotropin Releasing Hormone (GnRH). GnRH then stimulates the
Pituitary Gland to produce
Luteinizing Hormone (LH), and LH stimulates the
Testicles to produce testosterone. Finally, testosterone from the testicles and dehydroepiandrosterone from the
Adrenal Gland s stimulate the prostate to produce more DHT. Hormonal therapy can decrease levels of DHT by interrupting this pathway at any point.
There are several forms of hormonal therapy:
- Orchiectomy is surgery to remove the testicles. Because the testicles make most of the body's testosterone, after orchiectomy testosterone levels drop. Now the prostate not only lacks the testosterone stimulus to produce DHT, but also it does not have enough testosterone to transform into DHT.
- Antiandrogens are medications such as Flutamide , Bicalutamide , Nilutamide , and Cyproterone Acetate which directly block the actions of testosterone and DHT within prostate cancer cells.
- Medications which block the production of adrenal androgens such as DHEA include Ketoconazole and Aminoglutethimide . Because the adrenal glands only make about 5% of the body's androgens, these medications are generally used only in combination with other methods that can block the 95% of androgens made by the testicles. These combined methods are called total androgen blockade (TAB). TAB can also be achieved using antiandrogens.
- GnRH action can be interrupted in one of two ways. GnRH Antagonists suppress the production of LH directly, while GnRH Agonists suppress LH through the process of Downregulation after an initial stimulation effect. Abarelix is an example of a GnRH antagonist, while the GnRH agonists include Leuprolide , Goserelin , Triptorelin , and Buserelin . Initially, GnRH agonists ''increase'' the production of LH. However, because the constant supply of the medication does not match the body's natural production rhythm, production of both LH and GnRH decreases after a few weeks.57 Erratum in: J Clin Oncol. 2004 November 1;22(21):4435.
As Of 2006 the most successful hormonal treatments are orchiectomy and GnRH agonists. Despite their higher cost, GnRH agonists are often chosen over orchiectomy for cosmetic and emotional reasons. Eventually, total androgen blockade may prove to be better than orchiectomy or GnRH agonists used alone.
Each treatment has disadvantages which limit its use in certain circumstances. Although orchiectomy is a low-risk surgery, the psychological impact of removing the testicles can be significant. The loss of testosterone also causes
Hot Flashes , weight gain, loss of
Libido , enlargement of the
Breast s (
Gynecomastia ), impotence and
Osteoporosis . GnRH agonists eventually cause the same side effects as orchiectomy but may cause worse symptoms at the beginning of treatment. When GnRH agonists are first used, testosterone surges can lead to increased bone pain from metastatic cancer, so antiandrogens or abarelix are often added to blunt these side effects. Estrogens are not commonly used because they increase the risk for
Cardiovascular Disease and
Blood Clots . The antiandrogens do not generally cause impotence and usually cause less loss of bone and muscle mass. Ketoconazole can cause
Liver Damage with prolonged use, and aminoglutethimide can cause skin
Rash es.
Palliative Care for advanced stage prostate cancer focuses on extending life and relieving the symptoms of metastatic disease.
Chemotherapy may be offered to slow disease progression and postpone symptoms. The most commonly used regimen combines the chemotherapeutic drug
Docetaxel with a
Corticosteroid such as
Prednisone .
58 Bisphosphonates such as
Zoledronic Acid have been shown to delay skeletal complications such as
Fracture s or the need for radiation therapy in patients with hormone-refractory metastatic prostate cancer.
59
Bone Pain due to metastatic disease is treated with
Opioid Pain Relievers such as
Morphine and
Oxycodone . External beam radiation therapy directed at bone metastases may provide
Pain relief. Injections of certain
Radioisotope s, such as
Strontium-89 ,
Phosphorus-32 , or
Samarium-153 , also target bone metastases and may help relieve pain.
HIFU for prostate cancer utilizes
High Intensity Focused Ultrasound (HIFU) to ablate/destroy the tissue of the prostate. During the
HIFU procedure, sound waves are used to heat the prostate tissue thus destroying the cancerous cells. Essentially, ultrasonic waves are precisely focused on specific areas of the prostate to eliminate the prostate cancer with minimal risks of effecting other tissue or organs. Temperatures at the focal point of the sound waves can exceed 100oC.Thomas A. Gardner and Michael A Koch, Indiana University Medical Center, Indianapolis. Prostate Cancer Therapy with High-Intensity Focused Ultrasound-Comprehensive Review. Clinical Genitourinary Cancer Vol 4. No.3, 2005. In lay terms, the
HIFU technology is similar to using a magnifying glass to burn a piece of paper by focusing sunlight at a small precise point on the sheet. The ability to focus the ultrasonic waves leads to a relatively low occurrence of both
Incontinence and
Impotence . (0.6% and 0-20%, respectively)Toyoaki Uchida, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Dept of Urology University of Tokai Hachioji Hospital. International Journal of Urology According to international studies, when compared to other procedures,
HIFU has a high success rate with a reduced risk of side effects. Studies using the Sonablate 500
HIFU machine have shown that 94% of patients with a pretreatment PSA (
Prostate Specific Antigen ) of less than 10 g/ml were cancer-free after three years.Toyoaki Uchida, et al. Five years experience of transrectal high-intensity focused ultrasound using the Sonablate device in the treatment of localized prostate cancer. Dept of Urology University of Tokai Hachioji Hospital. International Journal of Urology However, many studies of HIFU were performed by manufacturers of HIFU devices, or members of manufacturers' advisory panels.Tom Pickles, Larry Goldenberg, Gary Steinhoff. High Intensity Focused Ultrasound for Prostate Cancer. British Columbia Cancer Agency http://www.bccancer.bc.ca/NR/rdonlyres/08EA1C8E-4345-4C7E-A83A-1F84853A1C27/8101/HIFUreport2005Feb10revised1.pdf
HIFU was first used in the 1940’s and 1950’s in efforts to destroy tumors in the central nervous system. Since then,
HIFU has been shown to be effective at destroying malignant tissue in the brain, prostate, spleen, liver, kidney, breast, and bone.Thomas A. Gardner and Michael A Koch, Indiana University Medical Center, Indianapolis. Prostate Cancer Therapy with High-Intensity Focused Ultrasound-Comprehensive Review. Clinical Genitourinary Cancer Vol 4. No.3, 2005. Today, the
HIFU procedure for prostate cancer is performed using a transrectal probe. This procedure has been performed for over ten years and is currently approved for use in Japan, Europe, Canada, and parts of Central and South America.
Although not yet approved for use in the Unites States, many patients have received the
HIFU procedure at facilities in Canada, and Central and South America.
Currently, therapy is available using the Sonablate 500 or the Ablatherm. The Sonablate 500 is designed by Focus Surgery of Indianapolis, Indiana and is used in international HIFU centers around the world.
Prostate cancer rates are higher and prognosis poorer in developed countries than the rest of the world. Many of the risk factors for prostate cancer are more prevalent in the , death from prostate cancer was one-fifth to one-half the rates in the United States and
Europe in the 1990s.
61 Review. In
India in the 1990s, half of the people with prostate cancer confined to the prostate died within ten years.
62 African-American men have 50–60 times more prostate cancer and prostate cancer deaths than men in
Shanghai ,
China .
63 In
Nigeria , two percent of men develop prostate cancer and 64% of them are dead after two years.
64
In patients who undergo treatment, the most important clinical prognostic indicators of disease outcome are stage, pre-therapy PSA level and Gleason score. In general, the higher the grade and the stage, the poorer the prognosis.
Nomogram s can be used to calculate the estimated risk of the individual patient. The predictions are based on the experience of large groups of patients suffering from cancers at various stages.
65
In 1941,
Polyphenols , a potential alternative therapy for prostate cancer by natural compounds, has been shown to inhibit the development, progression, and
Metastasis as well in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which spontaneously develops prostate cancer.Gupta S, Hastak K, Ahmad N, Lewin JS, Mukhtar H. Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Proc Natl Acad Sci U S A. 2001 August 28;98(18):10350-5. PMID 11504910
''' (right), who was awarded the 1966
Nobel Prize for his research on prostate cancer, is shown with 1937 Nobel laureate
Albert Szent-Gyorgyi .]]
Although the prostate was first described by This surgical approach allowed for removal of the prostate and lymph nodes with maintenance of penile function.
In 1941 in reproduction was determined by
Andrzej W. Schally and
Roger Guillemin , who both won the 1977 Nobel Prize in Physiology or Medicine for this work.
Receptor agonists, such as
Leuprolide and
Goserelin , were subsequently developed and used to treat prostate cancer.Schally, A. V., Kastin, A. J. & Arimura, A. ''Hypothalamic FSH and LH-regulating hormone. Structure, physiology and clinical studies.'' Fertil. Steril. 22, 703–721 (1971).Tolis G, Ackman D, Stellos A, Mehta A, Labrie F, Fazekas AT, Comaru-Schally AM, Schally AV. ''Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists.'' Proc Natl Acad Sci U S A. 1982 Mar;79(5):1658–62 PMID 6461861
Radiation Therapy for prostate cancer was first developed in the early 20th century and initially consisted of intraprostatic
Radium implants. External beam radiation became more popular as stronger radiation sources became available in the middle of the 20th century. Brachytherapy with implanted seeds was first described in 1983.Denmeade SR, Isaacs JT. ''A History of Prostate Cancer Treatment.'' Nature Reviews Cancer 2, 389–396 (2002). PMID 12044015 Systemic chemotherapy for prostate cancer was first studied in the 1970s. The initial regimen of
Cyclophosphamide and
5-fluorouracil was quickly joined by multiple regimens using a host of other systemic chemotherapy drugs.Scott, W. W. et al. ''Chemotherapy of advanced prostatic carcinoma with cyclophosphamide or 5-fluorouracil: results of first national randomized study.'' J. Urol. 114, 909–911 (1975). PMID 1104900
