Prostate cancer

Other Name : Carcinoma of the man’s prostate,adenocarcinoma, or glandular cancer

Definition:
Prostate cancer is cancer that occurs in a man’s prostate— a small walnut-shaped gland that produces the seminal fluid that nourishes and transports sperm for  male reproductive system.

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Prostate cancer is one of the most common types of cancer in men. Most prostate cancers are slow growing; however, some grow relatively fast.Initially remains confined to the prostate gland,  where it may not cause serious harm. While some types of prostate cancer grow slowly and may need minimal or no treatment, other types are aggressive and can spread quickly.

Prostate cancer that is detected early — when it’s still confined to the prostate gland — has a better chance of successful treatment.

Factors that increase the risk of prostate cancer include: older age, a family history of the disease, and race. About 99% of cases occur in those over the age of 50. Having a first degree relative with  the disease increases the risk 2 to 3 fold. In the United States it is more common in the African American population than the Caucasian population. Other factors that may be involved include a diet  high in processed, red meat, or milk products or low in certain vegetables. Prostate cancer is diagnosed by biopsy. Medical imaging may then be done to determine if the cancer has spread to other  parts of the body.

Symptoms:
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), and dysuria (painful urination). A study  based on the 1998 Patient Care Evaluation in the US found that about a third of patients diagnosed with prostate cancer had one or more such symptoms, while two thirds had 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:
The  causes of prostate cancer  is still not very clear.
Doctors know that prostate cancer begins when some cells in your prostate become abnormal. Mutations in the abnormal cells’ DNA cause the cells to grow and divide more rapidly than normal cells  do. The abnormal cells continue living, when other cells would die. The accumulating abnormal cells form a tumor that can grow to invade nearby tissue. Some abnormal cells can break off and  spread (metastasize) to other parts of the body.

Risk Factors:
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 30% of men in their 50s, and in 80% 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.   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 factors :
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 40% 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.

Two large genome-wide association studies linking single nucleotide polymorphisms (SNPs) to prostate cancer were published in 2008. These studies identified several SNPs which substantially  affect the risk of prostate cancer. For example, individuals with TT allele pair at SNP rs10993994 were reported to be at 1.6 times higher risk of prostate cancer than those with the CC allele pair. This

SNP explains part of the increased prostate cancer risk of African American men as compared to American men of European descent, since the C allele is much more prevalent in the latter; this SNP is located in the promoter region of the MSMB gene, thus affects the amount of MSMB protein synthesized and secreted by epithelial cells of the prostate.

Dietary factors:
While some dietary factors have been associated with 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.  Higher meat consumption has been associated with a higher risk in some studies.

Lower blood levels of vitamin D may increase the risk of developing prostate cancer.

Folic acid supplements have no effect on the risk of developing prostate cancer.

Viral factors:
In 2006, a previously unknown retrovirus, Xenotropic MuLV-related virus or XMRV, was associated with human prostate tumors,  but subsequent reports on the virus were contradictory,  and the original 2006 finding was instead due to a previously undetected contamination.

Sexual factors:
Several case-control studies have shown that having many lifetime sexual partners or starting sexual activity early in life substantially increases the risk of prostate cancer. This correlation suggests  a sexually transmissible infection (STI) may cause some prostate cancer cases; however, many studies have unsuccessfully attempted to find such a link, especially when testing for STIs shortly  before or after prostate cancer diagnosis.  Studies testing for STIs a decade or more prior to prostate cancer diagnosis find a significant link between prostate cancer and various STIs (HPV-16, HPV-18 and HSV-2). This evidence could be explained by a yet-to-be-identified sexually transmissible infection and a long latency period between onset of infection and prostate cancer.

On the other hand, while the available evidence is weak,  tentative results suggest that frequent ejaculation may decrease the risk of prostate cancer.  A study, over eight years, showed that those  that ejaculated most frequently (over 21 times per month on average) were less likely to get prostate cancer.  The results were broadly similar to the findings of a smaller Australian study

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.

Pathophysiology:
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 3 centimeters long and weighs about 20 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 20 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.

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-?B 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.

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.

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) the man should  talk to the doctor about the pros and cons of testing so  the person can decide if testing is the right choice for  him.”

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.

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.

Prostate screening tests :

*Digital rectal exam (DRE). During a DRE, your doctor inserts a gloved, lubricated finger into your rectum to examine your prostate, which is adjacent to the rectum. If your doctor finds any
abnormalities in the texture, shape or size of your gland, you may need more tests.

*Prostate-specific antigen (PSA) test. A blood sample is drawn from a vein in your arm and analyzed for PSA, a substance that’s naturally produced by your prostate gland. It’s normal for a small  amount of PSA to be in your bloodstream. However, if a higher than normal level is found, it may be an indication of prostate infection, inflammation, enlargement or cancer.
PSA testing combined with DRE helps identify prostate cancers at their earliest stages, but studies have disagreed whether these tests reduce the risk of dying of prostate cancer. For that reason,  there is debate surrounding prostate cancer screening.

If an abnormality is detected on a DRE or PSA test, your doctor may recommend tests to determine whether you have prostate cancer, such as:

*Ultrasound. If other tests raise concerns,  the doctor may use transrectal ultrasound to further evaluate your prostate. A small probe, about the size and shape of a cigar, is inserted into  the rectum. The probe uses sound waves to make a picture of the  prostate gland.

*Collecting a sample of prostate tissue. If initial test results suggest prostate cancer, your doctor may recommend a procedure to collect a sample of cells from your prostate (prostate biopsy).

Prostate biopsy is often done using a thin needle that’s inserted into the prostate to collect tissue. The tissue sample is analyzed in a lab to determine whether cancer cells are present.

Now to Determining whether prostate cancer is aggressive:

When a biopsy confirms the presence of cancer, the next step is to determine the level of aggressiveness (grade) of the cancer cells. In a laboratory, a pathologist examines a sample of the cancer cell to determine how much cancer cells differ from the healthy cells. A higher grade indicates a more aggressive cancer that is more likely to spread quickly.

The most common scale used to evaluate the grade of prostate cancer cells is called a Gleason score. Scoring combines two numbers and can range from 2 (nonaggressive cancer) to 10 (very aggressive cancer).

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For  determining how far the cancer has spread:

Once a prostate cancer diagnosis has been made, your doctor works to determine the extent (stage) of the cancer. If your doctor suspects your cancer may have spread beyond your prostate, imaging tests such as these may be recommended:

*Bone scan
*Ultrasound
*Computerized tomography (CT) scan
*Magnetic resonance imaging (MRI)
*Positron emission tomography (PET) scan

It is not every person should have every test. The doctor will determine which tests are best for  every  individual case.

Once testing is complete,  the doctor assigns the stage and this helps determination of  treatment options. The prostate cancer stages are:

Stage I. This stage signifies very early cancer that’s confined to a small area of the prostate. When viewed under a microscope, the cancer cells aren’t considered aggressive.

Stage II. Cancer at this stage may still be small but may be considered aggressive when cancer cells are viewed under the microscope. Or cancer that is stage II may be larger and may have grown to  involve both sides of the prostate gland.

Stage III. The cancer has spread beyond the prostate to the seminal vesicles or other nearby tissues.

Stage IV. The cancer has grown to invade nearby organs, such as the bladder, or spread to lymph nodes, bones, lungs or other organs.

Treatment:
Prostate cancer treatment options depend on several factors, such as how fast your cancer is growing, how much it has spread and the overall health  and age of the patient , as well as the benefits  and the potential side effects of the treatment.Immediate treatment may not be necessary for men diagnosed with very early-stage of  prostate cancer. Some men may never need treatment. Instead, doctors sometimes recommend active  surveillance.

In active surveillance, regular follow-up blood tests, rectal exams and possibly biopsies may be performed to monitor progression of your cancer. If tests show your cancer is progressing, you may opt for a prostate cancer treatment such as surgery or radiation.

Active surveillance may be an option for cancer that isn’t causing symptoms, is expected to grow very slowly and is confined to a small area of the prostate. Active surveillance may also be

considered for a man who has another serious health condition or an advanced age that makes cancer treatment more difficult.

Active surveillance carries a risk that the cancer may grow and spread between checkups, making it less likely to be cured.

For other cases the the following treatment is recomended:

*Radiation therapy : Radiation therapy uses high-powered energy to kill cancer cells. Prostate cancer radiation therapy can be delivered in two ways:

Radiation that comes from outside of  the body (external beam radiation). During external beam radiation therapy, the patient   lie on a table while a machine moves around the body, directing high-

powered energy beams, such as X-rays or protons, to   prostate cancer.The patient  typically undergo external beam radiation treatments five days a week for several weeks.

Radiation placed inside  the body (brachytherapy). Brachytherapy involves placing many rice-sized radioactive seeds in your prostate tissue. The radioactive seeds deliver a low dose of radiation

over a long period of time. The doctor implants the radioactive seeds in patient’s prostate using a needle guided by ultrasound images. The implanted seeds eventually stop giving off radiation and  don’t need to be removed.

Side effects of radiation therapy can include painful urination, frequent urination and urgent urination, as well as rectal symptoms, such as loose stools or pain when passing stools. Erectile dysfunction can also occur.

Hormone therapy:
Hormone therapy is treatment to stop  the patient’s body from producing the male hormone testosterone. Prostate cancer cells rely on testosterone to help them grow. Cutting off the supply of hormones may cause cancer cells to die or to grow more slowly.

Options of hormone therapy:
*Medications that stop the body from producing testosterone. Medications known as luteinizing hormone-releasing hormone (LH-RH) agonists prevent the testicles from receiving messages to make testosterone. Drugs typically used in this type of hormone therapy include leuprolide (Lupron, Eligard), goserelin (Zoladex), triptorelin (Trelstar) and histrelin (Vantas). Other drugs sometimes used include ketoconazole and abiraterone (Zytiga).

*Medications that block testosterone from reaching cancer cells. Medications known as anti-androgens prevent testosterone from reaching your cancer cells. Examples include bicalutamide (Casodex), flutamide, and nilutamide (Nilandron). The drug enzalutamide (Xtandi) may be an option when other hormone therapies are no longer effective.

Surgery to remove the testicles (orchiectomy).
Removing  the testicles reduces testosterone levels in the body.
Hormone therapy is used in men with advanced prostate cancer to shrink the cancer and slow the growth of tumors. In men with early-stage prostate cancer, hormone therapy may be used to shrink tumors before radiation therapy. This can make it more likely that radiation therapy will be successful.

Side effects of hormone therapy may include erectile dysfunction, hot flashes, loss of bone mass, reduced sex drive and weight gain.

Surgery to remove the prostate:
Surgery for prostate cancer involves removing the prostate gland (radical prostatectomy), some surrounding tissue and a few lymph nodes. Ways the radical prostatectomy procedure can be performed include:

*Using a robot to assist with surgery. During robot-assisted surgery, the instruments are attached to a mechanical device (robot) and inserted into  the abdomen through several small incisions. The surgeon sits at a console and uses hand controls to guide the robot to move the instruments. Robotic prostatectomy may allow the surgeon to make more-precise movements with surgical tools than is possible with traditional minimally invasive surgery.

*Making an incision in  the abdomen. During retropubic surgery, the prostate gland is taken out through an incision in  the lower abdomen. Compared with other types of prostate surgery, retropubic prostate surgery may carry a lower risk of nerve damage, which can lead to problems with bladder control and erections.

*Making an incision between  the anus and scrotum. Perineal surgery involves making an incision between  the anus and scrotum in order to access  the prostate. The perineal approach to surgery may allow for quicker recovery times, but this technique makes removing the nearby lymph nodes and avoiding nerve damage more difficult.

*Laparoscopic prostatectomy. During a laparoscopic radical prostatectomy, the doctor performs surgery through small incisions in the abdomen with the assistance of a tiny camera (laparoscope). This procedure requires great skill on the part of the surgeon, and it carries an increased risk that nearby structures may be accidentally cut. For this reason, this type of surgery is not commonly performed for prostate cancer in the U.S. anymore.

The Doctor should decide which type of surgery is best for  the specific situation.

Radical prostatectomy carries a risk of urinary incontinence and erectile dysfunction. The riskfactors that the patient   may face based on the situation, the type of procedure the patient may select, according to his age, body type and  overall health.

Freezing of prostate tissue:
Cryosurgery or cryoablation involves freezing tissue to kill cancer cells.

During cryosurgery for prostate cancer, small needles are inserted in the prostate using ultrasound images as guidance. A very cold gas is placed in the needles, which causes the surrounding tissue to freeze. A second gas is then placed in the needles to reheat the tissue. The cycles of freezing and thawing kill the cancer cells and some surrounding healthy tissue.

Initial attempts to use cryosurgery for prostate cancer resulted in high complication rates and unacceptable side effects. However, newer technologies have lowered complication rates, improved cancer control and made the procedure easier to tolerate. Cryosurgery may be an option for men who haven’t been helped by radiation therapy.

Chemotherapy:
Chemotherapy uses drugs to kill rapidly growing cells, including cancer cells. Chemotherapy can be administered through a vein in your arm, in pill form or both.

Chemotherapy may be a treatment option for men with prostate cancer that has spread to distant areas of their bodies. Chemotherapy may also be an option for cancers that don’t respond to hormone therapy.

Biological therapy:
Biological therapy (immunotherapy) uses your body’s immune system to fight cancer cells. One type of biological therapy called sipuleucel-T (Provenge) has been developed to treat advanced, recurrent prostate cancer.

This treatment takes some of the patient’s own immune cells, genetically engineers them in a laboratory to fight prostate cancer, then injects the cells back into your body through a vein. Some men do respond to this therapy with some improvement in their cancer, but the treatment is very expensive and requires multiple treatments.

Alternative therapy:
It is believed that regular Yoga exercise with Pranayama  and Meditation under the guideline of some expart  may help a lot to cope with the distress of the patient.

Prevention:
Diet and lifestyle

The data on the relationship between diet and prostate cancer is poor.   In light of this the rate of prostate cancer is linked to the consumption of the Western diet.  There is little if any evidence to support an association between trans fat, saturated fat and carbohydrate intake and risk of prostate cancer.  Evidence regarding the role of omega-3 fatty acids in preventing prostate cancer does not suggest that they reduce the risk of prostate cancer, although additional research is needed. Vitamin supplements appear to have no effect and some may increase the risk.  High calcium intake has been linked to advanced prostate cancer. Consuming fish may lower prostate cancer deaths but does not appear to affect its occurrence.  Some evidence supports lower rates of prostate cancer with a vegetarian diet.  There is some tentative evidence for foods containing lycopene and selenium.  Diets rich in cruciferous vegetables, soy, beans and other legumes may be associated with a lower risk of prostate cancer, especially more advanced cancers.

Men who get regular exercise may have a slightly lower risk, especially vigorous activity and the risk of advanced prostate cancer.

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Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://en.wikipedia.org/wiki/Prostate_cancer
http://www.mayoclinic.org/diseases-conditions/prostate-cancer/basics/definition/con-20029597

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