PROSTATE CANCER

PROSTATE CANCER is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize (spread) from the prostate to other parts of the body, particularly the bones and lymph nodes. Prostate cancer may cause pain, difficulty in urinating, problems during sexual intercourse, or erectile dysfunction. Other symptoms can potentially develop during later stages of the disease.

Rates of detection of prostate cancers vary widely across the world, with South and East Asia detecting less frequently than in Europe, and especially the United States. Prostate cancer tends to develop in men over the age of fifty. Globally it is the sixth leading cause of cancer-related death in men (in the United States it is the second). Prostate cancer is most common in the developed world with increasing rates in the developing world. However, many men with prostate cancer never have symptoms, undergo no therapy, and eventually die of other unrelated causes. Many factors, including genetics and diet, have been implicated in the development of prostate cancer.

The presence of prostate cancer may be indicated by symptoms, physical examination, prostate-specific antigen (PSA), or biopsy. Prostate-specific antigen testing increases cancer detection but does not decrease mortality. The United States Preventive Services Task Force in 2012 recommended against screening for prostate cancer using the PSA testing, due to the risk of over-diagnosis and over-treatment with most prostate cancer remaining asymptomatic. The USPSTF concludes that the potential benefit of testing does not outweigh the expected harms.

Management strategies for prostate cancer should be guided by the severity of the disease. Many low-risk tumors can be safely followed with active surveillance. Curative treatment generally involves surgery, various forms of radiation therapy, or, less commonly, cryosurgery; hormonal therapy and chemotherapy are generally reserved for cases of advanced disease (although hormonal therapy may be given with radiation in some cases).

The age and underlying health of the man, the extent of metastasis, appearance under the microscope and response of the cancer to initial treatment are important in determining the outcome of the disease. 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.

SIGNS and SYMPTOMS of Prostate Cancer

Early prostate cancer usually causes no symptoms. Sometimes, however, prostate cancer does cause symptoms, often similar to those of diseases such as benign prostatic hyperplasia. These include frequent urination, nocturia (increased urination at night), difficulty starting and maintaining a steady stream of urine, hematuria (blood in the urine), anddy suria (painful urination). About a third of patients diagnosed with prostate cancer have one or more such symptoms, while two thirds have no symptoms.

Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra. Changes within the gland, therefore, directly affect urinary function. Because the vas deferens deposits seminal fluid into the prostatic urethra, and secretions from the prostate gland itself are included in semen content, prostate cancer may also cause problems with sexual function and performance, such as difficulty achieving erection or painful ejaculation.

Advanced prostate cancer can spread to other parts of the body, possibly causing additional symptoms. The most common symptom is bone pain, often in the vertebrae (bones of the spine), pelvis, or ribs. Spread of cancer into other bones such as the femur is usually to the proximal part of the bone. Prostate cancer in the spine can also compress the spinal cord, causing leg weakness and urinary and fecal incontinence.

CAUSES of Prostate Cancer

A complete understanding of the causes of prostate cancer remains elusive. The primary risk factors are obesity, age and family history. Prostate cancer is very uncommon in men younger than 45, but becomes more common with advancing age. The average age at the time of diagnosis is 70. 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. Men who have first-degree family members with prostate cancer appear to have double the risk of getting the disease compared to men without prostate cancer in the family. This risk appears to be greater for men with an affected brother than for men with an affected father. In the United States in 2005, there were an estimated 230,000 new cases of prostate cancer and 30,000 deaths due to prostate cancer. Men with high blood pressure are more likely to develop prostate cancer. There is a small increased risk of prostate cancer associated with lack of exercise. A 2010 study found that prostate basal cells were the most common site of origin for prostate cancers.

Genetic

Genetic background may contribute to prostate cancer risk, as suggested by associations with race, family, and specific gene variants. Men who have a first-degree relative (father or brother) with prostate cancer have twice the risk of developing prostate cancer, and those with two first-degree relatives affected have a fivefold greater risk compared with men with no family history. In the United States, prostate cancer more commonly affects black men than white or Hispanic men, and is also more deadly in black men. In contrast, the incidence and mortality rates for Hispanic men are one third lower than for non-Hispanic whites. Studies of twins in Scandinavia suggest that forty percent of prostate cancer risk can be explained by inherited factors.

No single gene is responsible for prostate cancer; many different genes have been implicated. Mutations in BRCA1 and BRCA2, important risk factors for ovarian cancer and breast cancer in women, have also been implicated in prostate cancer. Other linked genes include the Hereditary Prostate cancer gene 1 (HPC1), the androgen receptor, and the vitamin D receptor. TMPRSS2-ETS gene family fusion, specifically TMPRSS2-ERG or TMPRSS2-ETV1/4 promotes cancer cell growth.

Loss of cancer suppressor genes, early in the prostatic carcinogenesis, have been localized to chromosomes 8p, 10q, 13q,and 16q. P53 mutations in the primary prostate cancer are relatively low and are more frequently seen in metastatic settings, hence, p53 mutations are late event in pathology of prostate cancer. Other tumor suppressor genes that are thought to play a role in prostate cancer include PTEN (gene) and KAI1. "Up to 70 percent of men with prostate cancer have lost one copy of the PTEN gene at the time of diagnosis" Relative frequency of loss of E-cadherin and CD44 has also been observed.

Dietary

While a number of dietary factors have been linked to prostate cancer the evidence is still tentative. Evidence supports little role for dietary fruits and vegetables in prostate cancer occurrence. Red meat and processed meat also appear to have little effect in human studies. Evidence from animals studies however raise concerns. Lower blood levels of vitamin D 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.

Green tea may be protective (due to its catechins content), although the most comprehensive clinical study indicates that it has no protective effect. Other holistic methods are also studied.

Taking multivitamins more than seven times a week may increase the risks of contracting the disease. This research was unable to highlight the exact vitamins responsible for this increase (almost double), although they suggest that vitamin A, vitamin E and beta-carotene may lie at its heart. It is advised that those taking multivitamins never exceed the stated daily dose on the label. Higher selenium blood levels have been associated with a lower risk of prostate cancer, a trial of supplementation however did not find benefit.

Folic acid supplements have recently been linked to an increase in risk of developing prostate cancer. A ten-year study led by University of Southern California researchers showed that men who took daily folic acid supplements of 1 mg were three times more likely to be diagnosed with prostate cancer than men who took a placebo.

High alcohol intake may increase the risk of prostate cancer and interfere with folate metabolism. Low folate intake and high alcohol intake may increase the risk of prostate cancer to a greater extent than the sole effect of either one by itself. A case control study consisting of 137 veterans addressed this hypothesis and the results were that high folate intake was related to a 79% lower risk of developing prostate cancer and there was no association between alcohol consumption by itself and prostate cancer risk. Folate's effect however was only significant when coupled with low alcohol intake. There is a significant decrease in risk of prostate cancer with increasing dietary folate intake but this association only remains in individuals with low levels of alcohol consumption. There was no association found in this study between folic acid supplements and risk of prostate cancer.


Medication exposure

There are also some links between prostate cancer and medications, medical procedures, and medical conditions. Use of the cholesterol-lowering drugs known as the statins may also decrease prostate cancer risk.

Infection or inflammation of the prostate (prostatitis) may increase the chance for prostate cancer while another study shows infection may help prevent prostate cancer by increasing blood to the area. In particular, infection with the sexually transmitted infections chlamydia, gonorrhea, or syphilis seems to increase risk. Finally, obesity and elevated blood levels of testosterone may increase the risk for prostate cancer. There is an association between vasectomy and prostate cancer however more research is needed to determine if this is a causative relationship.

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.

Viral

In 2006, researchers associated a previously unknown retrovirus, Xenotropic MuLV-related virus or XMRV, with human prostate tumors. Subsequent reports on the virus have been contradictory. A group of US researchers found XMRV protein expression in human prostate tumors, while German scientists failed to find XMRV-specific antibodies or XMRV-specific nucleic acid sequences in prostate cancer samples.

PATHOPHYSIOLOGY - Prostate Cancer

The prostate is a part of the male reproductive system that helps make and store seminal fluid. In adult men, a typical prostate is about three centimeters long and weighs about twenty grams. 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. Because of its location, prostate diseases often affect urination, ejaculation, and rarely defecation. The prostate contains many small glands which make about twenty percent of the fluid constituting semen. In prostate cancer, the cells of these prostate glands mutate into cancer cells. The prostate glands require male hormones, known as androgens, to work properly. Androgens include testosterone, which is made in the testes; dehydroepiandrosterone, made in the adrenal glands; and dihydrotestosterone, which is converted from testosterone within the prostate itself. Androgens are also responsible for secondary sex characteristics such as facial hair and increased muscle mass.

When normal cells are damaged beyond repair, they are eliminated by apoptosis. 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 bloodstream and lymphatic system. Prostate cancer is considered a malignant tumor because it is a mass of cells that can invade other parts of the body. This invasion of other organs is called metastasis. Prostate cancer most commonly metastasizes to the bones, lymph nodes, and may invade rectum, bladder and lower ureters after local progression. The route of metastasis to bone is thought to be venous as the prostatic venous plexus draining the prostate connects with the vertebral veins.

The prostate is a zinc accumulating, citrate producing organ. The protein ZIP1 is responsible for the active transport of zinc into prostate cells. One of zinc's important roles is to change the metabolism of the cell in order to produce citrate, an important component of semen. The process of zinc accumulation, alteration of metabolism, and citrate production is energy inefficient, and prostate cells sacrifice enormous amounts of energy (ATP) in order to accomplish this task. Prostate cancer cells are generally devoid of zinc. This allows prostate cancer cells to save energy not making citrate, and utilize the new abundance of energy to grow and spread. The absence of zinc is thought to occur via a silencing of the gene that produces the transporter protein ZIP1. ZIP1 is now called a tumor suppressor gene product for the gene SLC39A1. The cause of the epigenetic silencing is unknown. Strategies which transport zinc into transformed prostate cells effectively eliminate these cells in animals. Zinc inhibits NF-κB pathways, is anti-proliferative, and induces apoptosis in abnormal cells. Unfortunately, oral ingestion of zinc is ineffective since high concentrations of zinc into prostate cells is not possible without the active transporter, ZIP1.

RUNX2 is a transcription factor that prevents cancer cells from undergoing apoptosis thereby contributing to the development of prostate cancer.

The PI3k/Akt signaling cascade works with the transforming growth factor beta/SMAD signaling cascade to ensure prostate cancer cell survival and protection against apoptosis. X-linked inhibitor of apoptosis (XIAP) is hypothesized to promote prostate cancer cell survival and growth and is a target of research because if this inhibitor can be shut down then the apoptosis cascade can carry on its function in preventing cancer cell proliferation. Macrophage inhibitory cytokine-1 (MIC-1) stimulates the focal adhesion kinase (FAK) signaling pathway which leads to prostate cancer cell growth and survival.

The androgen receptor helps prostate cancer cells to survive and is a target for many anti cancer research studies; so far, inhibiting the androgen receptor has only proven to be effective in mouse studies. Prostate specific membrane antigen (PSMA) stimulates the development of prostate cancer by increasing folate levels for the cancer cells to use to survive and grow; PSMA increases available folates for use by hydrolyzing glutamated folates.

DIAGNOSIS

The American Cancer Society's position regarding early detection is "Research has not yet proven that the potential benefits of testing outweigh the harms of testing and treatment. The American Cancer Society believes that men should not be tested without learning about what we know and don’t know about the risks and possible benefits of testing and treatment. Starting at age 50, (45 if African American or brother or father suffered from condition before age 65) talk to your doctor about the pros and cons of testing so you can decide if testing is the right choice for you."

The only test that 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, less invasive testing can be conducted.

According to Professor Hardev Pandha, The Prostate Project Chair of Urological Oncology at the University of Surrey's Postgraduate Medical School, a non-invasive test looking for the presence of the protein Engrailed-2 (EN2) in the urine to be more reliable and accurate than existing tests.

"In this study, we showed that the new test was twice as good at finding prostate cancer as the standard PSA test. Only rarely did we find EN2 in the urine of men who were cancer free, so if we find EN2 we can be reasonably sure that a man has prostate cancer. EN2 was not detected in men with non-cancer disorders of the prostate such as prostatitis or benign enlargement. These conditions often cause a high PSA result, causing considerable stress for the patient and sometimes also unnecessary further tests such as prostate biopsies."

There are also several other tests that can be used to gather more information about the prostate and the urinary tract. Digital rectal examination (DRE) may allow a doctor to detect prostate abnormalities. 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.

DIAGNOSIS - Prostate Imaging

Ultrasound (US) and Magnetic Resonance Imaging (MRI) are the two main imaging methods used for prostate cancer detection. Urologists use transrectal ultrasound during prostate biopsy and can sometimes see a hypoechoic area. But US has poor tissue resolution and thus, is generally not clinically used. In contrast, prostate MRI has superior soft tissue resolution. MRI is a type of imaging that uses magnetic fields to locate and characterize prostate cancer. Multi-parametric prostate MRI consists of four types of MRI sequences called T2 weighted imaging, T1 weighted imaging, Diffusion Weighted Imaging, MR Spectrocopic Imaging and Dynamic-Contrast Enhanced Imaging. Genitourinary radiologists use multi-parametric MRI to locate and identify prostate cancer. Currently, MRI is used to identify targets for prostate biopsy using fusion MRI with ultrasound (US) or MRI-guidance alone. In men who are candidates for active surveillance, fusion MR/US guided prostate biopsy detected 33% of cancers compared to 7% with standard ultrasound guided biopsy.  Prostate MRI is also used for surgical planning for men undergoing robotic prostatectomy. It has also shown to help surgeons decide whether to resect or spare the neurovascular bundle, determine return to urinary continence and help assess surgical difficulty.  Some prostate advocacy groups believe prostate MRI should be used to screen for prostate cancer--"manogram"-- like mammogram is for breast cancer. NIH-funded clinical trials are underway to delineate the value of MRI for some of these applications

DIAGNOSIS - Prostate Biopsy

Prostate biopsy is a procedure in which small samples are removed from a man's prostate gland to be tested for the presence of cancer. It is typically performed when the scores from a PSA blood test rise to a level that is associated with the possible presence of prostate cancer.

The procedure, usually an outpatient procedure, requires a local anesthetic, with fifty-five percent of men reporting discomfort during the biopsy. The most frequent complication of the procedure is bleeding in the urine for several days, some bleeding in the stool for several days, and blood in the ejaculate for several weeks afterwards.

The procedure may be performed transrectally, through the urethra or through the perineum. The most common procedure is transrectal, and may be done with tactile finger guidance, or, more commonly and precisely, with ultrasound guidance.

About a dozen samples are taken from the prostate gland through a thin needle - about six from each side. If the procedure is performed transrectally, antibiotics are prescribed to prevent infection. An enema may also be prescribed for the morning of the procedure. In both the transrectal and the transperineal procedure, the doctor inserts an ultrasound probe into the rectum to help guide the biopsy needles. A local anesthetic is then administered into the tissue around the prostate, similar to the local anesthetic administered for a dental procedure. A spring-loaded prostate tissue collection needle is then inserted into the prostate, through the rectum (or more rarely through the perineum), about a dozen times. It makes a clicking sound, and there may be considerable discomfort.

Negative Biopsy

Biopsies detect prostate cancer in about 25% of men with abnormal screening tests. However a negative biopsy does not ensure the absence of disease. Repeat prostate biopsies are positive in about 25-30% of patients whose initial biopsy was negative.

During a biopsy procedure, less than 1 percent of the entire prostate gland is sampled, so men can harbor prostate cancer in spite of having a negative initial biopsy.

Recently in order to address this problem, researchers have examined the ability of mitochondrial DNA to help diagnose prostate cancer in negative biopsy samples.

Magnetic Resonance Imaging (MRI)-guided Biopsy

For the last two decades, transrectal ultrasound (TRUS) guided biopsy has been used to diagnose prostate cancer in a "blind" fashion because prostate cancer cannot be seen on ultrasound due to poor soft tissue resolution. MRI, in contrast, can identify and characterize prostate cancer. There are two forms of MRI-guided prostate biopsy: one that uses a fusion technology between US and MRI and another using MRI-alone. In the fusion US/MRI prostate biopsy, a prostate MRI is performed before biopsy and then, at the time of biopsy, the MRI images are fused to the ultrasound images to guide the urologist to the targets. In the second type of MRI-guided prostate biopsy, MRI is used at the time of biopsy. For US/MRI biopsy, a urologist performs the procedure whereas for MRI-guided prostate biopsy, a radiologist performs the procedure. US/MRI guided prostate biopsy has shown to be superior to standard TRUS-biopsy in prostate cancer detection. The multidisciplinary team approach between radiologists and urologists in prostate cancer diagnosis using MRI is benefiting men with prostate cancer. NIH-funded studies are underway to further clarify the benefits.

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.

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.^[

DIAGNOSIS - Gleason Score

The Gleason Grading system is used to help evaluate the prognosis of men with prostate cancer. Together with other parameters, it is incorporated into a strategy of prostate cancer staging which predicts prognosis and helps guide therapy. A Gleason score is given to prostate cancer based upon its microscopic appearance. Cancers with a higher Gleason score are more aggressive and have a worse prognosis.

PROCESS
Most often, a urologist or radiologist will remove a cylindrical sample (biopsy) of prostate tissue through the rectum, using hollow needles, and prepare microscope slides. After a prostate is removed in surgery, a pathologist will slice the prostate for a final examination.

GRADES and SCORES
The pathologist assigns a grade to the most common tumor pattern, and a second grade to the next most common tumor pattern. The two grades are added together to get a Gleason Score. For example, if the most common tumor pattern was grade 3, and the next most common tumor pattern was grade 4, the Gleason Score would be 3+4 = 7. The Gleason Grade is also known as the Gleason Pattern, and the Gleason Score is also known as the Gleason Sum. The Gleason Grade or Gleason Pattern ranges from 1 to 5, with 5 having the worst prognosis. The Gleason Score ranges from 2 to 10, with 10 having the worst prognosis. For Gleason Score 7, a Gleason 4+3 is a more aggressive cancer than a Gleason 3+4. Also, there is not really any difference between the aggressiveness of a Gleason Score 9 or 10 tumor.

PRIMARY, SECONDARY and TERTIARY

A pathologist examines the biopsy specimen and attempts to give a score to the two patterns.

• First called the primary grade, represents the majority of tumor (has to be greater than 50% of the total pattern seen).
• Second - a secondary grade - relates to the minority of the tumor (has to be less than 50%, but at least 5%, of the pattern of the total cancer observed).

These grades are then added to obtain the final Gleason score.

Increasingly, pathologists provide details of the "tertiary" component. This is where there is a small component of a third (generally more aggressive) pattern. So there could be a Gleason 3+4 with a tertiary component of pattern 5 - this would be considered to be more aggressive than a prostate cancer that was Gleason 3+4 with no tertiary pattern 5. Although it is debatable as to what the full extent the tertiary component has on the aggressiveness of a cancer.

HISTORY

The scoring system is named after Donald Gleason, a pathologist at the Minneapolis Veterans Affairs Hospital who developed it with other colleagues at that facility in the 1960s. It remains an important tool.

REFERENCE

1.  "Male Genital Pathology". Retrieved 2009-05-13.
2. Manage Account - Modern Medicine
3. Gleason, D. F. (1977). "The Veteran's Administration Cooperative Urologic Research Group: histologic grading and clinical staging of prostatic carcinoma". In Tannenbaum, M.. Urologic Pathology: The Prostate. Philadelphia: Lea and Febiger. pp. 171–198. ISBN 0-8121-0546-X.

DIAGNOSIS - Tumor Markers

Tissue samples can be stained for the presence of PSA and other tumor markers in order to determine the origin of malignant cells that have metastasized.

Small cell carcinoma is a very rare (1%) type of prostate cancer that cannot be diagnosed using the PSA. As of 2009 researchers are trying to determine the best way to screen for this type of prostate cancer because it is a relatively unknown and rare type of prostate cancer but very serious and quick to spread to other parts of the body. Possible methods include chromatographic separation methods by mass spectrometry, or protein capturing by immunoassays or immunized antibodies. The test method will involve quantifying the amount of the biomarker PCI, with reference to the Gleason Score. Not only is this test quick, it is also sensitive. It can detect patients in the diagnostic grey zone, particularly those with a serum free to total Prostate Specific Antigen ratio of 10-20%.

The oncoprotein BCL-2, has been associated with the development of androgen-independent prostate cancer due to its high levels of expression in androgen-independent tumours in advanced stages of the pathology. The upregulation of BCL-2 after androgen ablation in prostate carcinoma cell lines and in a castrated-male rat model further established a connection between BCL-2 expression and prostate cancer progression.

The expression of Ki-67 by immunohistochemistry may be a significant predictor of patient outcome for men with prostate cancer.

ERK5 is a protein that may be used as a marker. ERK5 is present in abnormally high levels of prostate cancer, including invasive cancer which has spread to other parts of the body. It is also present in relapsed cancer following previous hormone therapy. Research shows that reducing the amount of ERK5 found in cancerous cells reduces their invasiveness.

DIAGNOSIS - Classification

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 nodes, 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 scans 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 metastasis—opposite to what is found in many other cancers that metastasize.

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.

SCREENING of Prostate Cancer

Prostate cancer screening is an attempt to find unsuspected cancers, and may lead to more invasive follow-up tests such as a biopsy, with cell samples taken for closer study. Options include the digital rectal exam (DRE) and the prostate-specific antigen (PSA) blood test. Such screening is controversial and, in some people, may lead to unnecessary, even harmful, consequences. Routine screening with either a DRE or PSA is not supported by the evidence as there is no mortality benefit from screening.

The United States Preventive Services Task Force (USPSTF) recommends against the PSA test for prostate cancer screening in healthy men regardless of age. The USPSTF concludes that the potential benefit of testing does not outweigh the expected harms, "Prostate-specific antigen–based screening results in small or no reduction in prostate cancer–specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary." The Centers for Disease Control and Prevention shared that conclusion. The American Society of Clinical Oncology (ASCO) recommends screening be discouraged in those who are expected to live less than ten years, while in those with a life expectancy of greater than ten years a decision should be made by the person in question based on the potential risks and benefits.

Regular Consultation with the Doctor to Prevent Prostate Cancer

PREVENTION of Prostate Cancer

PREVENTION

There is a significant relation between lifestyle (including food consumption) and cancer prevention.

Medications

Two medications which block the conversion of testosterone to dihydrotestosterone, finasteride and dutasteride, have also shown some promise. The use of these medications for primary prevention is still in the testing phase, and they are not widely used for this purpose. A 2008 study found that finasteride reduces the incidence of prostate cancer by 30%, without any increase in the risk of High-Grade prostate cancer. In the original study it turns out that the smaller prostate caused by finasteride means that a doctor is more likely to hit upon cancer nests and more likely to find aggressive-looking cells.

Taking 5-alpha-reductase inhibitors (5-ARIs) can reduce a man’s risk of being diagnosed with prostate cancer from around 5–9% to around 4-6% during up to 7 years of treatment.

Ejaculation frequency

More frequent ejaculation also may decrease a man's risk of prostate cancer. One study showed that men who ejaculated 3-5 times a week at the age of 15-19 had a decreased rate of prostate cancer when they are old, though other studies have shown no benefit. The results contradict those of previous studies, that suggested that having many sexual partners, or a high frequency of sexual activity, increases the risk of prostate cancer by up to 40 percent. A key difference may be that these earlier studies defined sexual activity as sexual intercourse, whereas this study focused on the number of ejaculations, whether or not intercourse was involved. An explanation for this discrepancy may be that sex with partners increases the risk of contracting sexually transmitted diseases, including cryptic infections, which increase the risk of cancers. Another study completed in 2004 reported that "Most categories of ejaculation frequency were unrelated to risk of prostate cancer. However, high ejaculation frequency was related to decreased risk of total prostate cancer." The report abstract concluded, "Our results suggest that ejaculation frequency is not related to increased risk of prostate cancer."

Diet

It is recommended that people maintain a normal weight (limiting consumption of energy dense foods and sugary drinks), eat plant based food, limit red and processed meat, and limit alcohol. Some evidence supports a vegetarian or vegan diet.  Consuming fish appears to lower prostate cancer deaths but not the occurrence of prostate cancer. Omega-3 fatty acids are unlikely to prevent prostate cancer. There is no evidence that vitamin supplements affect risk. Trans fats may be associated with an increased risk of cancer but the evidence is still limited.

MANAGEMENT PROSTATE CANCER

The first decision to be made in managing prostate cancer is whether any treatment at all is needed. Prostate cancer, especially the most common, low-grade forms found in the typical elderly patient, often grows so slowly that no treatment is required at all. Donald Gleason, the inventor of the Gleason score, advocated for renaming the very common 3+3 prostate "cancer" to prostate adenosis, because he believed it so unlikely to harm the patient. Treatment may also be inappropriate or impossible if the patient has other serious health problems or is not expected to live long enough for symptoms to appear.

Which option is best depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors are age, general health, and patient views about potential treatments and their possible side effects. Because all treatments can have significant side effects, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations. A combination of the treatment options is often recommended for managing prostate cancer.

The National Comprehensive Cancer Network (NCCN) offers evidence-based guidelines for prostate cancer that can guide treatment choices for specific clinical situations. This requires a good estimation of the patient's long-term health-adjusted life expectancy, because this factor is the most important determinant of survival in newly diagnosed patients. A simplified approach shows how to estimate health-adjusted life expectancy and apply the NCCN guidelines so that patients can have a roadmap to reach the decision recommended for their clinical situation, which they can alter according to their personal values, including fear of cancer and fear of side effects.

Patients can also use a newly developed 18-item questionnaire to learn whether they have good knowledge and understanding about their treatment options before they choose an option. Most newly diagnosed patients who have already made a treatment choice can not correctly answer over half of the questions.

The selection of treatment options involves many factors. For example, if radiation therapy is done first, and fails, then radical prostatectomy is a very technically challenging surgery and may not be feasible. On the other hand, radiation therapy done after surgical failure may have many complications. The desire to maximize subsequent options in case of failure may affect the treatment decision.

MANAGEMENT PROSTATE CANCER - Active Surveillance

Active surveillance

Many men diagnosed with low-risk prostate cancer are eligible for active surveillance. This term implies careful observation of the tumor over time, with the intention of treatment for cure if there are signs of cancer progression. Active surveillance is not synonymous with watchful waiting, an older term which implies no treatment or specific program of monitoring, with the assumption that palliative, not curative, treatment would be used if advanced, symptomatic disease develops.

Active surveillance involves monitoring the tumor for signs of growth or the appearance of symptoms. The monitoring process may involve serial PSA, physical examination of the prostate, and/or repeated biopsies. The goal of surveillance is to avoid over-treatment and the sometimes serious, permanent side effects of treatment for a slow-growing or self-limited tumor that would never cause any problems for the patient. This approach is not used for aggressive cancers, but it may cause anxiety for patients who wrongly believe that all cancer is deadly or themselves to have a life-threatening cancer.

For the 50% to 75% of patients with prostate cancer that will cause no harm before the man dies of something unrelated, active surveillance may be the best choice.

MANAGEMENT PROSTATE CANCER - Aggressive Cancer

Aggressive cancer

Treatment for aggressive prostate cancers involves surgery (i.e. radical prostatectomy), radiation therapy including brachytherapy (prostate brachytherapy) and external beam radiation therapy, High-intensity focused ultrasound (HIFU), chemotherapy, oral chemotherapeutic drugs (Temozolomide/TMZ), cryosurgery, hormonal therapy, or some combination.

Because of PSA screening, almost 90% of patients are diagnosed when the cancer is localized to the prostate gland and its removal by surgery or radiotherapy will in most cases lead to a cure. Because of this almost 94% of U.S. patients choose treatment. However, in 50% to 75% of these patients the cancer would not have affected their survival even without treatment, and by accepting treatment they have a high chance of sexual, urinary, and bowel side effects. For instance, two-thirds of treated patients cannot get sufficient erections for intercourse, and almost a third have urinary leakage. However, some cancers will grow faster and prostate cancer is the second most common reason of cancer death in U.S. men, after lung cancer.

Radiation Therapy

Although the widespread use of prostate specific antigen (PSA) screening in the USA has resulted in diagnosis at earlier age and cancer stage, the vast majority of cases are still diagnosed in men older than 65 years, and approximately 25% of cases are diagnosed in men older than 75 years. Though US National Comprehensive Cancer Network guidelines recommend using life expectancy greater than or less than 10 years to help make treatment decisions, in practice, many elderly patients are not offered curative treatment options such as radical prostatectomy (RP) or radiation therapy and are instead treated with hormonal therapy or watchful waiting. This pattern can be attributed to factors such as medical co-morbidity and patient preferences is regard to quality of life in addition to prostate cancer specific risk factors such as pretreatment PSA, Gleason score and clinical stage. As the average life expectancy increases due to advances in treatment of cardiovascular, pulmonary and other chronic disease, it is likely that more elderly patients will be living long enough to suffer the consequences of their prostate cancer. Therefore, there is currently much interest in the role of aggressive prostate cancer treatment modalities such as with surgery or radiation in the elderly population who have localized disease. The results of one randomized controlled trial published by the Scandinavian Prostate Cancer Group 4  evaluated cancer-specific mortality in patients treated with RP compared with watchful waiting. The patients receiving radical prostatectomy had a relative risk reduction of 30.7% [95% confidence interval 2.5%-50.7%], but an absolute risk reduction of 6% [95% confidence interval 0.5%-11.5%]. The number needed to treat was calculated to be 16. This means that, over the median follow up period of approximately 10 years, 16 patients with localized prostate cancer would need to receive radical prostatectomy rather than watchful waiting in order to prevent one death due to prostate cancer. Further subset analysis revealed that this benefit did not apply to all ages equally. In men younger than 65 years, patients randomized to receive radical prostatectomy actually had a 10-18% absolute risk reduction in cancer-specific mortality compared to those randomized to watchful waiting. However, in men older than 65, there was no statistically significant risk reduction even when adjusted for PSA level, Gleason score and tumor stage. Randomized, controlled trials comparing radical prostatectomy, radiation therapy, hormonal therapy and watchful waiting would provide the best evidence for how to best treat elderly patients.

If the cancer has spread beyond the prostate, treatment options significantly change, so most doctors that treat prostate cancer use a variety of nomograms to predict the probability of spread. Treatment by watchful waiting/active surveillance, external beam radiation therapy, brachytherapy, cryosurgery, HIFU, and surgery are, in general, offered to men whose cancer remains within the prostate. Hormonal therapy and chemotherapy are often reserved for disease that has spread beyond the prostate. However, there are exceptions: radiation therapy may be used for some advanced tumors, and hormonal therapy is used for some early stage tumors. Cryotherapy (the process of freezing the tumor), hormonal therapy, and chemotherapy may also be offered if initial treatment fails and the cancer progresses.

A vaccine, sipuleucel-T has been found result in a benefit ( a four month increase in survival ) for men with metastatic prostate cancer.

SOURCE: www.en.wikipedia.org