1. INTRODUCTION
2. CAUSES OF PROSTATE CANCER
3. RISK FACTORS
4. PATHOLOGY AND SPREAD
5. SIGNS AND SYMPTOMS
6. SCREENING
7. DIAGNOSIS
8. STAGING AND GRADING OF PROSTATE CANCER
9. COMPLICATIONS
10. TREATMENT
11. PREVENTION
12. CONCLUSION

Complications from prostate cancer are related to both the disease and its treatment. In fact, one of the biggest fears of many men who have prostate cancer is that their treatment may leave them incontinent or impotent. Fortunately, these side effects aren't always permanent and therapies exist to help cope with or treat the conditions.

The typical complications of prostate cancer and its treatments include:

1. Spread of cancer: Prostate cancer can spread to nearby organs and bones and can be life threatening.

2. Pain: Although early-stage prostate cancer typically isn't painful, once it has progressed to nearby bones, it may produce intense pain. Pain relievers or radiation are used to relieve the pain.

3. Incontinence: Both prostate cancer and its treatment can cause incontinence. Overall, about 10 percent of men experience incontinence after prostate cancer treatments such as radiation or surgery to remove the prostate.

4. Impotence (Erectile dysfunction): Like incontinence, erectile dysfunction can be a result of prostate cancer or its treatment, including surgery and radiation.

5. Depression: Many men may develop feelings of depression after a diagnosis of prostate cancer or after trying to cope with the side effects of treatment. These feelings may last for only a short time, they may come and go or they may linger for weeks or months.

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Treatment of prostate cancer depends on the stage and the grade of tumour. Other important factors in planning treatment are the man's age, general health and his feelings about the treatment options and their possible side effects.

Treating with the intent of cure is of limited value in men older than 70 years of age. Therefore the approach to treating prostate cancer in the geriatric population is not the same as in younger men. At that age more emphasis is given to relief of symptoms. The most common treatments for prostate cancer include the following:

1.Watchful Waiting

2. Surgery

• Retropubic prostatectomy
• Perineal prostatectomy
• Transurethral resection of the prostate

3. Radiation

• External beam radiation
• Three-dimensional conformal radiation therapy (3-D CRT)
• Seed Implantation (Brachytherapy):

4. Freezing Cancer Cells (Cryotherapy):

5. Hormonal therapy

• Orchiectomy
  
• Estrogens
  
• GnRH Agonist
  
• Antiandrogens

6. Chemotherapy

7. Immunotherapy

8. Biologic agents

9. Complementary and alternative medicine

1. Watchful Waiting
Watchful waiting is a conservative approach in which patients are routinely followed with serum PSA, DRE, and evaluation of local symptoms. These tests are performed about every 6 months. No immediate treatment is given for the diagnosed prostate cancer. With progression of cancer, local symptoms may develop and require intervention.

Watchful waiting is not the best treatment for all men and can allow cancer that is at a highly treatable stage to grow and spread. This approach is generally not recommended if the person is healthy and young. In a young patient, the cancer has many years to grow, and even a small, slow growing cancer might eventually reach the point when it needs additional treatment. The cancer cells could also unexpectedly become aggressive and spread so much that a cure becomes difficult or impossible.

For patients older than 70 years with moderately differentiated, low volume prostate cancer and a life expectancy of fewer than 10 years or significant comorbidity, watchful waiting is probably the best treatment option.

2. Surgery
The most effective way to treat cancer confined to prostate gland is to remove the gland. This type of surgery is called radical prostatectomy. Research indicates that cancer recurs in nearly 30 percent of men who undergo the procedure. But it has better long-term results than any other therapies, especially in men with a life expectancy of 10 years or more.

During a radical prostatectomy, surgeons use special techniques to cut free the prostate, while trying to spare muscles and attached nerve bundles that control urination and sexual function.

Retropubic prostatectomy: In retropubic surgery, the gland is taken out through an incision in the lower abdomen that typically runs from just below the navel to an inch above the penis. It's the most common form of prostate removal because the same incision can be used to remove surrounding lymph nodes, which are tested to make sure the cancer hasn't spread. In addition, the procedure gives the surgeon better access to the prostate, making it easier to save the nerve bundles that control erection.

Perineal prostatectomy: An incision is made between the anus and the scrotal sac holding the testicles. There's generally less bleeding with perineal surgery. Unfortunately, this approach makes it much more difficult to locate and save the nerve bundles attached to the prostate. In addition, the surgeon isn't able to reach nearby lymph nodes. That's why this surgery is less commonly used.

Transurethral resection of the prostate: In this method part of the prostate is removed with an instrument that is inserted through the urethra. The cancer is cut from the prostate by electricity passing through a small wire loop on the end of the instrument. This method is mainly used to remove tissue that blocks urine flow.

Note: Some times the lymph nodes are removed before doing a prostectomy. If the cancer has not spread to the lymph nodes, then the prostate is removed. If cancer has spread to the nodes, the prostate is not removed; instead a different mode of treatment is suggested.

The main complications of surgery are blood loss, rectal laceration, incontinence and impotence. When nerve-sparing surgery is performed, impotence may be only temporary.

Men who have prostectomy no longer produce semen. Men who wish to father children may therefore consider sperm banking or sperm retrieval procedure before surgery.

3. Radiation
Radiation treatment uses high-powered X-rays or other radiation to kill cancer cells. Like surgery it is a local therapy therefore it can affect cancer cells only in the treated area.

In early stages radiation can be used instead of surgery, or it may be used after surgery to destroy any cancer cells that may remain in the area.
In advanced stages it may be given to relieve pain or other problems.

It's generally the preferred treatment if patient is old or in poor health and might have a hard time withstanding surgery. For cancer confined to the prostate, radiation is often as effective as surgery for as much as 10 years. However, localised cancer may recur in men after radiation treatment.

Radiation also is used to treat cancer that has spread outside prostate. It can destroy cancerous cells, shrink tumours and relieve painful symptoms. A new study indicates that men may have a better chance at surviving advanced prostate cancer if suppression of the hormone androgen is used in combination with radiotherapy.

There are three forms of radiation therapy:

External beam radiation: External beam radiation is the more commonly used procedure. A beam from a large machine placed over body delivers radiation. Unfortunately, these "external beams" do more than destroy cancerous cells. They can damage healthy tissue in the same area. Treatments are generally given 5 days a week for about 6 or 7 weeks.

Radiation induced morbidities can occur early or late in the course of treatment. Acute side effects include radiation proctitis, radiation cystitis, diarrhoea, and fatigue. Late toxicities include chronic proctitis, and cystitis, incontinence, impotence and urethral strictures.

Three-dimensional conformal radiation therapy (3-D CRT): A new and promising external beam therapy known as three-dimensional conformal radiation therapy (3-D CRT) uses protons instead of X-rays to kill the cancer. Protons are parts of atoms that cause little damage to surrounding tissue but effectively destroy cells at the end of the beam. This allows delivery of stronger doses of beam radiation.

Seed Implantation (Brachytherapy): This method allows insertion of radioactive seeds directly into the prostate. Various isotopes, including iodine-125 and palladium-103 are available. These seeds deliver double the dose of radiation of external beams and the seeds cause less damage to healthy tissue.

Limitation of this technique involves the nonhomogenous distribution of interstitial seed implantation, which may lead to poor long-term outcomes. Current practice involves ultrasound guided or CT-guided placement.
Seed implants generally produce fewer side effects than external beam radiation. But impotence does occur in about 1 out of 6 men. Incontinence is rare.

4. Freezing Cancer Cells (Cryotherapy)
Another way to kill prostate cancer is to freeze the prostate using cryotherapy. Cryotherapy involves inserting 5 to 7 thin metal rods, each about 6 inches long, through the perineum and into the prostate. An ultrasound probe in the rectum helps in positioning the rods.

Fig.3 Targeted cryosurgery for prostate cancer

Once the rod tips are in place, liquid nitrogen is released into the rods, where it circulates and plunges the temperature to about minus 374 F. As the tissue around the rods freezes, the formation and expansion of ice crystals within the cancerous cells cause them to rupture and die. To keep the urethra from freezing along with the prostate, a catheter is placed inside the urethra and filled with a warming solution.

Short-term results are encouraging, with cryotherapy controlling cancer confined to the prostate in about 80 percent of men. But the long-term survival rates appear lower than with surgery or radiation. In addition, the procedure doesn't always kill all the cancer cells and may have to be repeated. Impotence results from cryotherapy 90 percent of the time.

5. Hormonal Therapy
Hormonal therapy has been and remains the gold standard treatment for advanced or metastatic prostate cancer. The circulation of male sex hormones in the body makes the cancer grow faster, therefore the most common way to treat advanced prostate cancer is to cut off the supply of these hormones.

Hormonal therapy cannot cure prostate cancer but is used as effective palliative therapy. All methods of hormonal therapy work by blocking different steps of androgen production, secretion, or function.

About 75 percent of men with advanced prostate cancer choose this form of treatment. Hormone therapy uses drugs to stop body from producing most male sex hormones or block hormones from getting into cancer cells. Sometimes a combination of drugs is used to do both.

Hormone therapy is sometimes used in combination with surgery and radiation in early-stage cancers. The hormones shrink large tumours so that surgery or radiation can destroy them more easily. After these treatments, the drugs can help kill stray cells left behind at the tumour site.

There are several treatment options available to achieve Androgen deprivation. These are as follows:

Table 4. Methods of hormonal therapy:

Bilateral orchiectomy, Estrogens and GnRH Agonist reduce testicular androgens but adrenal androgens are still produced. These can be blocked with Antiandrogens. Antiandrogens block the action of both testicular and adrenal androgen at the tumour receptor site. However, at the doses currently studied as monotherapy, blockade is incomplete. Therefore the increasingly accepted practice is that of maximal androgen blockade (MAB), in which an antiandrogen is combined with surgical or chemical castration, thus ablating testicular androgen while also opposing stimulation from the residual adrenal androgens.

Cytoproterone acetate is a steroidal antiandrogen and is associated with undesirable side effects like thrombophlebitis, fluid retention, lossof libido and cardiac side effects.

Bicalutamide, Flutamide and Nilutamide are nonsteroidal and are regarded as pure antiandrogens.

Bicalutamide has an advantage over others due to a longer half-life and can therefore be given once daily. Side effects are breast tenderness, gynaecomastia and hot flashes. The sexual potency and functioning is generally maintained.

Prostate cancer that has spread to other parts of the body can usually be controlled with hormonal therapy for a period of time, often several years. Eventually, however, most prostate cancers are able to grow with very little or no male hormones. When this happens, hormonal therapy is no longer effective.

The timing of hormonal therapy is controversial. There are different views on whether it should be instituted early, delayed or intermittently. The concept of intermittent therapy allows patient to experience the benefits of hormonal therapy as well as improved quality of life, reduced toxicity and cost of therapy and recovery of sexual function.

6. Chemotherapy
Recently there has been renewed interest in the use of cytotoxics to treat advanced prostate cancer particularly Hormone refractory prostate cancer (HRPC). A number of trials have been performed in the last decade to evaluate the role of chemotherapy in prostate cancer. Mitoxantrone, estramustine, etc. are being used either alone or with prednisone for treating HRPC. CT-2584, is also being evaluated for HRPC.

Chemotherapy has a role in the palliative treatment of patients with advanced prostate cancer. Its use is in patients with adequate bone marrow and organ function who have significant tumour burden or rapidly progressive disease.

7. Immunotherapy
Immunotherapy is a rapidly emerging therapeutic modality in prostate cancer treatment. Trials have focused on enhancing the host immune response with the goal of achieving tumour rejection.

Recently a new vaccine has been developed that may boost the body's own immune system to help combat prostate cancer. Currently it is being tested for effectiveness. This vaccine is composed of a fragment of the prostate-specific antigen (PSA) protein.

8. Biologic agents
Advances in the understanding of prostate cancer biology have led to the development of drugs directed against precise molecular alterations in the prostate tumor cell. Biologic agents now in development include:

• Inhibitors of signal transduction,
  
• Angiogenesis inhibitors,
  
• Pro-apoptic agents,
  
• Cell cycle inhibitors, and
  
• Monoclonal antibodies.
  

9. Complementary and alternative medicine: A range of dietary supplement and herbal medicines are being explored for prevention and treatment of prostate cancer and cancer in general. Some of these are showing promise and slowly gaining acceptance in the mainstream medicine. Benefits and risks of most of these remain unproved by scientific methods.

One of these is a herb named saw palmetto (Serenoa repens). Unlike other herbal supplements, it has been widely tested, and the results show promise.
Saw palmetto is thought to work by preventing testosterone from breaking down into another form of the hormone associated with prostate tissue growth. One drawback with this herb is that it may suppress PSA levels and lead to decreased effectiveness of PSA test.

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There is no single formula that can guarantee prostate cancer prevention, but certain measures can reduce risk or possibly slow the progression of disease.

High-fat diets have been linked to prostate cancer. Therefore, limiting intake of high-fat foods and emphasising on fruits, vegetables and whole fibers may help reduce prostate cancer risk. Foods rich in lycopenes, an antioxidant, may also help lower prostate cancer risk. These foods include raw or cooked tomatoes, tomato products, grapefruit and watermelon. Garlic and cruciferous vegetables such as broccoli, cabbage and cauliflower also appear to help fight cancer.

Prosate cancer is more common in western countries than Asian. The disparity in consumption of soy- based foods suggests that soy might have cancer prevention properties. Soy products contain isoflavones that seem to keep testosterone in check. Because prostate cancer feeds off testosterone, isoflavones may reduce the risk and progression of the disease.

Green tea contains a chemical called EGCC that also may help fight prostate cancer. Vitamin E has shown promise in reducing the risk of prostate cancer among smokers. More research is needed, however, to show the benefits of both green tea and vitamin E.
Several lines of evidence have implicated selenium, an essential trace element, in cancer prevention. In vitro studies suggest that selenium may potentiate antioxidant defences.

Studies indicate that regular exercise may reduce cancer risk, including prostate cancer. Exercise has been shown to strengthen immune system, improve circulation and speed digestion - all of which may play a role in cancer prevention. Exercise also helps to prevent obesity, another potential risk factor for prostate cancer.

The drug Finasteride is being studied in the prostate cancer prevention trial, which will complete in 2004.

According to recent studies, regular use of painkillers appears to protect older men against prostate cancer. However it should be borne in mind that regular use of these drugs can lead to other harmful effects like, stomach problems and liver damage.

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With the increase in geriatric population there is bound to be an increase in number of men with prostate cancer. The efficacy of current screening methods is doubtful therefore research ad trials are on to refine the tumor markers.
Treatment of both localised and advanced prostate cancer is controversial. Both watchful waiting and active intervention carry their own risk, so education of patient and his active participation in the decision making process are vital.

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