Prostate Cancer

written by Dr Git Kah Ann on 31 May 2012

PROSTATE CANCER

Dr. GIT Kah Ann
Consultant and Head of Department of Urology, Hospital Pulau Pinang,
Consultant Urologist, Pantai Hospital Penang.
 
Introduction
 
The prostate gland is a walnut shaped gland located between the bladder and the urethra and found only in men. The prostate enlarges with age and urine flows through it into the urethra. With age and male hormones called testosterone, the prostate grows. This growth will begin to narrow the urethra and obstructs the urine flow. That is why older men begin to have weaker flow as they grow older. The function of the prostate is to provide secretion and nutrition for the sperm.
 
What is cancer?
 
Our body is made up of trillions of living cells which grow, divide, and die in an orderly manner. Cancer begins when cells in a part of the body start to grow out of control. Cancer cells commonly grow more rapidly than normal cell and lose the ability to stop growing and dividing. These cancer cells also invade other tissues, something that normal cells cannot do. Tumour is when these cells become noticeable within an organ. When large enough the cancer cells will obtain the ability to spread and travel to other parts of the body. There they begin to grow and form new tumours that replace normal tissue and are called metastasis.
 
What is prostate cancer?
 
Cancer growing from prostate cells is called prostate cancer. Commonly they grow from prostate gland cells, so they are known as adenocarcinoma. Some prostate cancers can grow and spread quickly, but most of the time, prostate cancer grows slowly. Autopsy studies have shown that many men who died of other diseases also had prostate cancer that never caused a problem during their life-time. In many cases neither they nor their doctors even knew they had it. Hence the dictum “you will die WITH prostate cancer and NOT OF prostate cancer”.
 
 
Incidence and Risk Factor
 
The American Cancer Society's statistics showed that prostate cancer is the most common type of cancer found in American men and the second leading cause of cancer death in men, behind only to lung cancer. One man in 6 will get prostate cancer during his lifetime. And one man in 36 will die of this disease. In Malaysia, it is the fourth commonest cancer in men. Screening for prostate cancer is not frequently performed in Malaysia, hence the lower apparent incidence. Many prostate cancers have gone undiagnosed including many elderly men who have died and had their cause of death written off as “old-age”.
 
While we do not yet know exactly what causes prostate cancer, we do know that certain risk factors are linked to the disease. The risk factors include:
 
Age : Prostate cancer is very rare in men younger than 40. The chance of getting prostate cancer goes up quickly after a man reaches age 50 and almost 2 out of every 3 prostate cancers are found in men over the age of 65.
 
Ethnic : Prostate cancer is more common among the Indians followed by Chinese and Malays.
 
Family history : Prostate cancer seems to run in some families. Men with close family members (father, brother or uncle) who have had prostate cancer are more likely to get it themselves. Inherited genes raise prostate cancer risk but they probably account for only a small number of cases overall.
 
Diet : Men who eat a lot of red meat or high-fat dairy products seem to have a greater risk of getting prostate cancer than men who eat more fruits and vegetables. This is also linked to obesity in the first group of men.
 
Smoking : Smoking increases the risk of almost all cancers including prostate cancers but the linked is not clearly proven yet.
 
Making a diagnosis of prostate cancer
 
Prostate cancers are commonly diagnoses by one of two ways. Firstly is when the person is symptomatic and complaints of urinary symptoms such as frequency, poor urinary flow or backache. He sees a doctor and performs a digital rectal examination (DRE) and a blood test called prostate-specific antigen (PSA). It either of this test is positive, he will undergo a biopsy to confirm the diagnosis.
 
The other common method of diagnosis is by screening. It refers to performing the DRE and PSA on men without symptoms. Again, if either or both are elevated, he undergoes a definitive biopsy. Prostate cancer found by screening are usually at an early stage and frequently treatable, with better prognosis. Since the mid nineties in Malaysia, more men are diagnosed with prostate cancer but the death rates from prostate cancer have dropped due to PSA screening.
 
However uncontrolled and unnecessary PSA testing has its drawback. A mildly elevated PSA may heighten one’s anxiety and worry of prostate cancer which is frequently not the case. It would also lead on to many unnecessary prostate biopsies with more morbidity and complications as well as incurring the high cost of an avoidable biopsy test. It is recommended to consult a doctor before one embarks on a PSA test. The doctor will take into account one’s age, health and the benefits and side-effects of doing the test. In fact the American Cancer Society recommends that men are given a chance to make an informed decision with their doctor about whether to be screened for prostate cancer. They should first get information about what is known and what is not known about the risks and possible benefits of prostate cancer screening. Men should not be screened unless they have received this information.
 
DRE on the other hand is not as effective as PSA testing because it may be normal in men with very early prostate cancer. It is more useful in looking for spread of cancer beyond the prostate. It is an examination whereby the doctor inserts a lubricated gloved finger into the rectum to feel for the prostate located in front of the rectum.
 
Prostate Biopsy
 
Prostate biopsied are performed when there is a high suspicion of prostate cancer either by abnormal DRE, elevated PSA or both. It is done under ultrasound guidance from a probe inserted into the rectum usually performed by a urologist. He then injects local anaesthesia and inserts the core-biopsy needles into the prostate. The specimen is sent to the lab where the pathologist would be able to tell if these core-biopsy samples contain prostate cancer or not. The biopsy seems painful but with good local anaesthesia, the discomfort is greatly reduced.
 
If the biopsy is proven to contain cancer, the pathologist will go on to grade the cancer using “Gleason grading”. This would tell the urologist how aggressive is the cancer. He would also tell the location of the cancer involvement as well as the number of cores involved with cancer. This would give the urologist the necessary information to differentiate the cancer that will harm the patient as the saying goes “to differentiate the tiger from the pussy cat”.
 
Staging of prostate cancer
 
The first step to do after the diagnosis of prostate cancer is the stage the disease. It is broadly classified into:
 
1. Early prostate cancer
 
2. Locally-advanced prostate cancer
 
3. Metastatic prostate cancer
 
Staging tools includes, CT or MRI scans, essentially to look at the local prostate and lymph node spread; and bone scan which will look for bone metastasis. It is important to stage the cancer because subsequent treatment depends of the stage of the disease the patient is in.
 
Treatment of early prostate cancer
 
Early prostate cancer basically means cancer that is still confined to the prostate and has not spread to the surrounding structures, lymph nodes, bone or elsewhere. Treating at this stage offers the best chance of cure. The modalities of treatment include:
 
1. Active Surveillance.
This is essentially for very early and low-grade cancers. No aggressive treatment is given and the patient is followed up closely with PSA blood tests, digital rectal exams (DREs), and ultrasounds at regular intervals to see if the cancer is growing. Prostate biopsies may be done as well to see if the cancer is starting to grow faster. If there is a change in the test results, aggressive treatment options may be required.
 
2. Prostatectomy.
This in actual fact means surgical removal of the prostate gland and connecting the bladder back to the urethra. It can be performed either by open surgery, laparoscopic or robot-assisted laparoscopic prostatectomy. The earlier is by conventional open surgery to remove the cancerous prostate. The later two are key-hole surgeries to perform the same manoeuvres as open surgery but using laparoscopic instruments and looking at the operation site using a video-camera system.
 
Treatment of locally-advanced prostate cancer
 
Locally-advanced prostate cancer means the cancer has spread beyond the prostate to the surrounding organs in the absence of distant metastasis. Therefore treatment should be aimed at achieving local control of the disease. Often curative surgery is not possible at this stage because complete surgical clearance is often not possible. Leaving some cancer tissue behind will allow the cancer cells to grow again in greater speed and the patient would be left with the morbidity of surgery. This stage of cancer commonly requires radiotherapy and often it is combined with hormonal treatment. Hormonal treatment will be explained in the subsequent section.
 
Treatment of metastatic prostate cancer
 
Metastatic prostate cancer denotes cancer that has spread to a distant organ and treatment entails hormonal manipulation. The objective of treatment is to starve the cancer cells from the male hormone testosterone (androgen). Without testosterone, the cancer cells cannot grow and multiply. This treatment is known medically as “androgen deprivation therapy (ADT)”. The methods to achieve low levels of testosterone in the body consist of one of two treatment techniques. Firstly is to surgically remove the major source of testosterone, the testes. Surgical castration will essentially remove 98% of the testosterone; the remaining coming from the adrenal glands. This is almost always adequate ADT.
 
The other method is known as “medical castration” whereby the patient receives monthly or 3-monthly depot injections of a medicine called “luteinizing hormone releasing hormone (LHRH) analogue”. It works by a positive down-regulation of testosterone which after about two weeks after the first injection, the testosterone level will fall to a level similar to surgical castration. However the first two weeks of initiating treatment can cause a “flare phenomenon” which is an initial surge in testosterone levels before it is down-regulated. This flare can be counter-acted but taking an oral medication (anti-androgen) during the first month of treatment while waiting for the down-regulation to take effect.
 
Castation resistant prostate cancer (CRPC)
 
Castration be it surgical or medical castration usually are effective only for 3 to 5 years. The few hormonal resistant prostate cancer cells will continue to grow and multiply during the course of treatment with ADT. It would soon take over the prostate and its metastases and the cancer will before long continue to grow despite castration levels of testosterone. CRPC is usually detected when the PSA levels in the blood start to rise again after achieving a very low level initially during ADT. It is during this time that doctors will initiate chemotherapy which is given once every three weeks.
 
Like ADT, chemo is unlikely to result in a cure. This treatment is not expected to destroy all the cancer cells, but it may slow the cancer's growth and reduce symptoms, resulting in a better quality of life. It is usually at this terminal stage that patient’s priority is symptomatic palliative treatment aimed towards best quality of life rather than aggressive therapy with a lot of side effects.
 
Prostate cancer prevention
 
Can prostate cancer be prevented? This is usually the question in every man especially in men who have a relative diagnosed with prostate cancer. The answer is no but the risk can be reduced. As the risk factors were listed earlier to be unhealthy lifestyles, the way to reduce the risk is by adopting a healthy lifestyle of weight loss, exercise and a healthy diet. Vitamins and mineral were initially thought to be useful in preventing prostate cancer have been disproved recently in a large clinical trial, the SELECT trial.
 
Two drugs were recently shown to reduce the risk of developing prostate cancer. The drugs were initially designed as drugs to treat benign prostatic hyperplasia (BPH). However the prostate cancer properties were found and confirmed in two large prospective clinical trial respectively, the PCPT trial and the REDUCE trial. Unfortunately the risk reduction is modest and long term treatment is expensive and entails some side-effects. These undesirable side-effects include loss of libido and mild impotence.
 
 
 
 
1. American Cancer Society. http://www.cancer.org/Cancer/ProstateCancer/ MoreInformation/ProstateCancerEarlyDetection/prostate-cancer-early-detection-acs-recommendations