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Wednesday, January 11, 2012

Prostate Cancer

Introduction

Prostate cancer is malignant growth in the prostate gland. The prostate is a small, walnut-shaped gland that surrounds the bottom portion ("neck") of a male's bladder and about the first inch of the urinary tube (urethra), the channel that drains urine from the bladder. It is located behind the pubic bone and in front of the rectum. The prostate gland makes a thin, milky fluid that is part of semen, which contains sperm. It also helps keep germs (bacteria) from getting into the bladder.

It is the fifth most common cancer in Singapore men with an age-standardized incidence rate of 18.4 per 100,000 . Prostate cancer rates are the highest in Western countries and lowest in Asian countries. In Asia, however, the incidence of prostate cancer is significantly lower and it often plays second fiddle to lung, stomach and colon cancer. It is thus revealing that recent data from Asia have shown a general trend towards increasing incidence of prostate cancer, with some low-risk regions, such as Japan and Singapore, reporting a more rapid increase than some high-risk countries.

Prostate cancer, if detected early, is readily curable but up to now almost 30% of men with prostate cancer are being diagnosed when the disease has already spread. The prognosis of advanced prostate cancer is poor. Therefore, early diagnosis is of paramount importance.
Risk factors for prostate cancer

All men are at risk of developing prostate cancer during their lifetime. Some men, however, are at greater risk than others. Risk factors for prostate cancer include:
Age -- Prostate cancer can occur at any age, but most men who get prostate cancer are over 50. More than 80% are aged 65 years or older. With increasing sophistication of medical care and better nutrition, more Asians have a longer life expectancy. More men therefore live long enough for prostate cancer to be diagnosed.
Race or ethnicity -- African-American men are more at risk than white men. The reason for this is unknown. Prostate cancer occurs almost 70 percent more often in black men than it does in white American men. Black men are twice as likely to die of prostate cancer. Prostate cancer is more common in North America and northwestern Europe than in other areas of the world.
Family history (heredity, genetics) -- men who have a close (first-degree) male relative (father, brother, or son) who has had prostate cancer are at higher risk for getting prostate cancer. The more close relatives with prostate cancer a man has, the higher his risk.
Diet -- A high-fat diet and obesity may increase your risk of prostate cancer. Researchers theorize that fat increases production of the hormone testosterone, which may promote the development of prostate cancer cells. Obesity is often associated with a more sedentary lifestyle and decreased frequency of exercise. The association between obesity and prostate cancer stems from its influence on increasing circulating oestrogen level and decreasing androgen levels as androgens are aromatised to form oestrogen in adipose tissues. This may increase the prostate cell sensitivity to androgens and increase the risk of prostate cancer.

Symptoms
Prostate cancer often does not produce any symptoms in its early stages. That is why many cases of prostate cancer are not detected until they have spread beyond the prostate.
When signs and symptoms do occur, they may include the following:
A need to urinate frequently, especially at night
Difficulty starting urination or holding back urine
Inability to urinate
Weak or interrupted flow of urine
Painful or burning urination
Painful ejaculation
Blood in urine or semen; and/or
Frequent pain or stiffness in the lower back, hips, or upper thighs.

Any of the above symptoms can also be caused by things other than cancer, such as an enlarged prostate (benign prostatic hyperplasia, BPH) or an infection of the prostate. A man with these symptoms needs to see a doctor to find out the cause of the symptoms. It is important not to ignore these symptoms even if there is no pain.

Detection and diagnosis

Early detection and diagnosis of prostate cancer is important. If it is detected early, and it is in the early stage, the chances of successful treatment are better. There is lack of agreement among experts about whether routine screening of all men should be done.

Some experts believe that there is no clear evidence at this time that routine screening for early detection and treatment actually saves lives. The American College of Physicians recommends that rather than routine screening of all men for prostate cancer, doctors should describe the possible pros and cons (benefits and risks) of screening, diagnosis, and treatment.

The doctor should listen to the person’s concerns and then base the decision of whether to screen on the individual’s wishes. Others, such as the American Cancer Society, believe that the evidence supports screening for early detection, and that it can save lives.

Nowadays, prostate cancer frequently does not produce symptoms. The first indication of a problem may come during a routine screening test. Screening tests include:
Digital rectal exam (DRE). A quick and safe physical examination where the doctor inserts a gloved finger into the rectum to check for hard lump at an area where most prostate cancers first form.
Prostate-specific antigen (PSA) test. PSA is produced by both normal and malignant prostate cells; a PSA Blood Test can pick up an elevated PSA level, a warning sign. However, some men with BPH or prostatitis (inflamed prostate) have increased level of PSA without cancer.
Transrectal ultrasound and biopsy. Suspected prostate cancer through DRE and PSA can be confirmed through a biopsy – using Trans-rectal Ultrasound Scan (TRUS) to view and guide a needle into the prostate, the doctor would obtain small tissue samples for microscopic examination.
A biopsy is the only way to make the diagnosis of prostate cancer. The prostate tissue that is removed with a biopsy is placed under a microscope and is identified as to whether it is benign (not cancer) or malignant (cancer). If the biopsy tissue is malignant, the cancer is evaluated to give an estimate of how quickly it might grow and spread (grade) and how much the cancer has spread (stage).
Grading
A pathologist can assess a tumour’s aggressiveness, or potential to worsen within a short period of time. This is done using the Gleason Score, where a prostate biopsy’s appearance is graded and scored from 2 to 10. The more different the cancer cells are from the healthy cells, the more aggressive the cancer is and the more likely it is to spread quickly.

Cancer cells may vary in shape and size. The pathologist identifies the two most aggressive types of cancer cells when assigning a grade. The two most poorly differentiated areas of the biopsy tissue are graded from 1 to 5 and the two grades are added together. This is called the Gleason score. Gleason scores range from 2 to 10.

The scores are then grouped together and rated according to severity and the likely rate of growth and spread (aggressiveness) of the cancer:
Gleason score 2 - 4 = low grade
Gleason score 5 - 6 = intermediate (medium) grade
Gleason score 7 - 10 = high grade
Staging

After the level of aggressiveness of your prostate cancer is known, the next step, called staging, determines if or how far the cancer has spread. The newer system, the TNM system, is the preferred system. It is the most common staging system used in the United States. The doctor may use various blood and imaging tests to determine the stage of the disease. Treatment decisions depend on these findings.

Tests used in helping the doctor determine the stage of cancer may include:
Computed tomography (CT scan, CAT scan)
Magnetic resonance imaging (MRI)
Radionuclide bone scan
Prostacint scan (radioimmunoscintigraphy)
Biopsy of lymph nodes
Methods of Treatment
There are many types of treatment options available to men with prostate cancer. The method of treatment in cancer is based on many factors. The type of tumour, extent of disease at diagnosis (stage and grade), age, the overall health of the patient, life expectancy, and patient preferences are all considered in the decision about treatment. When making treatment choices, the benefits, risks, and possible side-effects of each type of treatment also need to be considered.
Watchful waiting
Sometimes, men are advised to wait to see if they need treatment. This is called watchful waiting. These men have regularly scheduled exams and tests to closely monitor their condition. Many men, especially older men, whose prostate cancer is slow growing and found at an early stage, may not need treatment.
Regular follow-up blood tests, rectal exams and possibly biopsies may be performed to monitor for evidence of progression of your cancer. Watchful waiting may be particularly appropriate if you're elderly, in poor health or both. Many such men will live out their normal life spans without treatment and without the cancer spreading or causing any problems. On the other hand, if a decision is made to treat the cancer, treatment options currently available include:

Surgery
Surgery -- a common treatment in early stages of prostate cancer. Surgery to remove the entire prostate is called radical prostatectomy. During this procedure, the surgeon uses special techniques to completely remove your prostate and local lymph nodes, while trying to spare muscles and nerves that control urination and sexual function. It may optimally treat cancer in its early stages and may help extend life in the later stages, however with possible side effects which may include impotence and urinary incontinence.
Three surgical approaches are available for a prostatectomy, retropubic, perineal and laparoscopic:
Retropubic surgery. In this approach, the gland is taken out through an incision in your lower abdomen that typically runs from just below your navel to an inch above the base of your penis.
Perineal surgery. With the perineal approach, an incision is made between your anus and scrotum. There's generally less bleeding with perineal surgery, and recovery time may be shorter, especially if you're overweight.
Robotic assisted laparoscopic surgery. The advent of robot-assisted laparoscopy signalled a new era in minimally invasive surgery, allowing surgeons to perform complex reconstructive procedures after radical prostatectomy with the benefit of reduced blood loss, less pain and quicker postoperative recovery.
Another type of surgery involves removing part of the prostate called a transurethral resection of the prostate (TURP). In this surgery, part of the prostate that surrounds the urethra is removed. This surgery is usually done on men who cannot have a radical prostatectomy because of other medical problems. It is also sometimes done before starting another kind of treatment. This surgery can relieve symptoms caused by the tumour, but does not cure the cancer because not all of the cancer will be removed with this surgery.
Radiation
In radiation therapy (also called radiotherapy), high-energy x-rays are used to damage and kill cancer cells and stop them from growing and dividing. Like surgery, radiation therapy is local therapy; it can affect cancer cells only in the treated area.
Unlike surgery, which is best used in early stage disease, radiation can be used in all stages of prostate cancer. It can be used as an alternative to surgery in localized disease, or it may be used after surgery to reduce the chance of recurrence when there is a high possibility that there are remaining cells in the area. In disease that has spread, it may be given to relieve pain or other problems.
There are two types of radiation therapy, external and internal.
External beam radiation uses a machine outside of the body to deliver high-energy x-rays beams to the specific area around the tumour. This is usually done on an outpatient basis, five days per week, for about seven weeks. Our very modern machines now have sophisticated technological capabilities such as 3-D Conformal Radiation Therapy and Intensity-Modulated Radiation Therapy.
Treatment is accurately planned and delivered with computer assistance. These advanced techniques allow high doses to deposited conformally around the tumour and adjacent areas which must be treated while reducing exposure to surrounding tissues which do not need to be treated.
Most men have mild side effects from this type of treatment, but most of the side effects resolve shortly after treatment is completed. Most men do not have problems with erections or intercourse immediately after radiation therapy. However, radiation can cause sexual side effects in some men later in life. During treatment some men experience urinary problems.
The most common signs and symptoms are urgency to urinate and frequent urination. These problems usually are temporary and gradually diminish in a few weeks after completing treatment. Long-term problems are uncommon.
Rectal problems such as loose bowel movements, scant rectal bleeding, discomfort during bowel movements and a sense that you have to have a bowel movement (rectal urgency) — may arise during treatment. Once the course of treatment is complete, these symptoms generally subside. However, a few men may continue to experience rectal problems months after treatment, but these improve on their own in most men.
Internal radiation is called brachytherapy. Brachytherapy is done by use of radioactive implants that may be permanent or temporary. Its main advantage over external beam treatment is its ability to deposit a higher dose to the tumour in the area encompassed by the radioactive sources while sparing or subjecting to a lower dose the adjacent normal tissues.
In temporary implants, small pellets of radioactive material on a string are inserted into the prostate. Once they are removed, there is no radioactivity in the body. Permanent implants are small radioactive seeds (pellets) that are inserted into the prostate. The pellets loose their radioactivity over time, which may be weeks or months. This therapy is generally used in men with smaller or moderate-sized prostates with small and lower-grade cancers. Sometimes, hormone therapy is used for a few months to shrink the size of the prostate before seeds are implanted.
Side effects of seed implants are somewhat different from those of external-beam radiation. Seed implants deliver a higher dose of radiation to your urethra causing urinary symptoms such as frequent, slower and painful urination to occur in nearly all men. Medication may be required to treat these symptoms, and some men require medications or the use of intermittent self-catheterisation to help them urinate.
Urinary symptoms tend to be more severe and longer lasting with seed implants than with external-beam radiation. Rectal symptoms, however, may be less frequent and less severe. Some men experience impotence due to radioactive seed implants.
Hormone therapy
This form of treatment prevents the prostate cancer from getting stimulated by the male hormones (androgens), which it needs for growth. It is usually used for prostate cancer that has metastasised. Hormone therapy can make the cancer stop growing or shrink, but it does not cure the cancer. There are several different hormone therapies including the removal of the testicles (orchiectomy), hormonal drugs, or chemicals. One approach uses luteinizing hormone-releasing hormone agonists (LHRH), given as shots (injections) to decrease the amount of testosterone made in the testicles. The female hormone estrogen, taken in pill form, is also sometimes used for this purpose. Other hormones called anti-androgens, given as pills, are used to stop the body from using androgens. Alternative hormones can be used if the initial ones stop working. Hormone therapy is sometimes given along with other types of treatment.
In most men with advanced prostate cancer, this form of treatment is effective in helping to slow the growth of tumours. Because it is effective in shrinking tumours, doctors use hormone therapy in some early-stage cancers in combination with radiation and sometimes with surgery. Hormones shrink large tumours so that surgery or radiation can remove or destroy them more easily. Given after these treatments, the drugs can inhibit the growth of stray cells left behind.
Simply depriving prostate cancer of testosterone does not usually kill all of the cancer cells. Within a few years, the cancer often learns to thrive without testosterone. Once this happens, hormone therapy is less likely to be effective. However, other treatment options still exist.
Side-effects of hormone therapy may include breast enlargement, reduced sex drive, impotence, hot flashes, weight gain and reduction in muscle and bone mass. Some of these drugs can also cause nausea, diarrhoea, fatigue and liver damage.
Chemotherapy
This type of treatment uses chemicals that destroy rapidly growing cells. Chemotherapy can be quite effective in treating prostate cancer, but it cannot cure it. Because it has more side effects than hormone therapy does, chemotherapy is often reserved for men who have hormone-resistant prostate cancer, especially if their cancer is causing symptoms.
Recently, two landmark randomised controlled trials demonstrated for the first time that overall survival for patients with metastatic hormone refractory prostate cancer can be improved with a systemic docetaxel-based combination chemotherapy.
Prevention
The huge difference in prostate cancer incidence rates between Asians and Caucasians have led investigators to compare differences in lifestyle and diet between Asians in their native countries and Asian migrants to high risk countries.
Early epidemiological studies suggested a possible causal association between dietary animal fat and prostate cancer.
Many other dietary factors have been studied with regards to prostate cancer risks and their roles may be summarized into two contributing causes:
1. as an influence on circulating androgens or oestrogens
2.
as a general protective effect against mitogens. Dietary factors that have been cited as a possible contributing factor to the low incidence in Asians include low dietary fat, isoflavonoids in soybeans, polyphenols in green tea, lycopene in cooked tomatoes, Selenium and Vitamin E.
Therefore, for a healthier diet that may reduce the risk of prostate cancer, we recommend a reduction of intake of red meat, dairy products, saturated fats, and egg yolk, and consumption of plenty of fruits and vegetables each day. The potential of selenium and vitamin E (taken alone or in combination) for preventing prostate cancer is currently being evaluated in a clinical trial.
Weber Lau
Senior Consultant
Dept of Urology
Singapore General Hospital

Terence Tan
Senior Consultant
Radiation Oncology
National Cancer Centre, Singapore

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