How Common Is Prostate Cancer?
This is a tumour of ageing males. It is rare below fifty years of age though more cases of men in their thirties and forties are being seen. This is a combination of improved screening and the possibility that prostate cancer prevalence is actually increasing. The actual new numbers of cases diagnosed each year is swelling as improved health leads to longer survival. This cancer is the second most common cancer in men after skin cancer of all types. It is second only to lung cancer as the most common cause of cancer related death in males. It is predicted that by 2006 it will have overtaken lung cancer. Three percent of men will die of the disease. The risk of prostate cancer is greater than breast cancer yet the education and awareness programs fall way behind that of breast cancer. The South African Government has NO program in place to improve public awareness of prostate cancer. One in six men will develop clinical prostate cancer in their lives versus one in eight women contracting breast cancer. Fatality rates for the two diseases are comparable. The life time risk of developing microscopic prostate cancer is 30%. Microscopic disease is very small and usually picked up by accident during procedures on prostates such as prostatic resections done for bladder obstruction. Microscopic disease cannot be felt or visualised on imaging modalities. As populations age and longevity increases this risk will increase. Microscopic disease however is not the same as clinical disease. Only half of the population with microscopic disease or fifteen percent of men will develop clinical disease. Also the older you are when microscopic disease is uncovered the less likely it will cause you trouble in your remaining lifetime. As a group of males? age, their numbers will decline through death from all causes but for the remaining members their chances of having microscopic disease will increase. At the age of ninety probably all of the remaining men in that group will have microscopic prostate cancer. Men over the age of seventy five should probably have no treatment if microscopic disease is diagnosed. Of course monitoring is advised to pick up the odd case that will progress to clinical disease.
What Increases The Risk Of Prostate Cancer?
In most prostate cancers, abnormal cells arise from the secretory cells of the prostate gland. These are the cells that make the prostatic fluid. The hallmark of all cancer cells is uncontrolled growth and the ability to escaper their site of origin and invades other regions of the body. Normal cells behave in a normal manner. This somewhat superficial statement needs to be explained. Normal cells can be likened to a civilised and peaceful nation. The cells are born, perform their occupation, interact peacefully with their neighbours and then they die. Cancer cells on the other hand are like an out of control mob of barbarians with no observance of societies norms. They multiply indiscriminately, they riot and cause local turmoil and destruction. They cause the deaths of normal cells and the eventual demise of the host nation they were born into through wide spread anarchy. As a cherry on the top these cells are immortal until they run out of food following the hosts? death. This abnormal behaviour stems from mutations in the DNA. All the cells normal functions are gradually rendered non-functional and completely bizarre behaviour or chaos ensues. Prostate cancer cells are no exception to this general behaviour of cancers. Prostate cancer cells initially resemble normal cells and their trouble making is minimal or non-existent. However with increasing mutational alterations of the DNA their behaviour and appearance becomes more unconventional. Progressive DNA mutations occur as the cells genes become more susceptible to injury and the abnormal cells survive or evade the body?s defence mechanisms against cancer cells. As the abnormal cells divide more frequently so more chances occur for further errors in DNA transcription leading to more abnormal genes. The genes drive all the functions of the cell. If the genes are abnormal then the cell will be abnormal. DNA mutations cause many different types of problems on the DNA strands. For example tumour suppressor genes become non-functional or even lost. These genes play a vital role in preventing cancers from occurring. Some genes called oncogenes can become expressed. These genes actually encourage the development of cancers in the host! Genes control all the cellular events that occur at any one time. There are genes for a whole host of functions. Just to mention a few there would be genes for cell repair, cell growth, cell messengers, cell respiration and enzyme production etc. Abnormalities of any of these genes will lead to abnormal cell behaviour. Typical characteristics of cancer cells caused by gene malfunction include loss of cell stickiness, production of enzymes to destroy surrounding tissue and barriers, production of proteins to attract new blood vessels so the tumour can grow and enhanced mechanisms for cell division. The rate of cell division increases with loss of cell normalcy. Cancer cells divide exponentially. That is one cell becomes two, then four, followed by eight, then sixteen etc. Each successive doubling period of the cell numbers is referred to as the doubling time. It takes twenty successive generations for one cell to become a million cells. Early tumour cells divide slowly with a two to four year doubling time. Aggressive undifferentiated tumours can double their numbers in months or weeks. This takes lots of energy and explains why people with advanced tumours become so ill and tired. Normal cells live in harmony with their neighbours and respect organ boundary lines. Cancer cells ignore this nicety and penetrate organ capsules, invade blood vessels and lymphatics and even use nerve channels for escape to more distant shores.
Specific Aspects of Prostate Cancer
In many men the initial prostate cancer cells probably occur in their thirties. These cells will often remain as a small microscopic focus of no clinical significance. What is the trigger that will convert a few quiescent cells into a rapidly growing aggressive disease is unknown. When this answer is discovered a whole new revolution will occur in the treatment of this disease. Ninety eight percent of prostate cancers are adenocarcinomas. These tumours arise as previously mentioned in the cells that line the glandular ducts where the prostatic fluid is manufactured. Initially these cells are confined to the glands by the basement membrane that surrounds the glands like the skin of a fruit. This condition is called prostatic intraepithelial neoplasia or PIN for short. This is a fancy term for a cancer that is not yet invasive and thus is considered ?safe? from the patients? point of view. PIN is graded according to the appearance of the cancer cells. Cells that are graded PIN I appear almost normal. In fact these changes are not really cancerous but rather dysplastic. Dysplasia is another technical term that means a precancerous condition. These cells may or may not evolve into a cancer. The body?s immune system may deal with these cells. PIN I is referred to as low grade PIN. Low grade PIN almost never causes a problem for the patient. Progressive abnormal changes in the cells are called PIN II and III or high grade PIN. These cells are cancerous but as previously mentioned they are confined by the basement membrane. Another term to describe this condition is carcinoma-in-situ. High grade PIN found in isolation in a prostate biopsy specimen is a strong predictor that subsequent biopsies will show invasive cancer. As many as 50% of patients with high grade PIN will have invasive cancer within two years of the initial biopsy. When the basement membrane containing the cells of the glandular duct is disrupted, the cancer cells can invade the surrounding prostatic tissue. The diagnosis of cancer is now made. As with PIN, prostate cancers are graded according to their appearance. Worsening grade is characterised by increasing loss of normal tissue structure.
Dr. Gleason described the progressive changes in architecture of prostate tumours and these changes correlated with increasing risk of rapid growth, spread and then demise of the patient. The Gleason score is numbered one to five. The total Gleason score is the sum of the scores of the two most prominent grades of tumour seen in a particular specimen. What does this mean? In any cancer not all the cell populations are at the same stage of carcinogenesis. Some cells appear less unpleasant than other cells. The most common cell type noted on the biopsy specimen is given the major Gleason grading. The second most common type is given the minor grading. Other cell types present are ignored. The two scores are combined to give a total out of a possible ten. For example a Gleason score of 3+2 would give an overall score of five. If the biopsy specimen has a uniform appearance of one cell type then the minor score will be the same as the major score. For example Gleason 3+3 equals an overall score of six.
In risk stratification for disease growth and spread, a Gleason score of less than five is considered favourable or low risk. A score of five to seven is an intermediate risk profile. Scores greater than seven imply a high risk of spread outside the gland. The Gleason score is one of the factors that your urologist will use to decide just how serious is your cancer and what form of treatment you should undergo. Other factors considered include your age, state of health, clinical stage of the cancer and PSA level.
What Is Tumour Staging?
Tumour staging assesses how far advanced is a tumour. Doctors? attempt to measure how large is the tumour within the prostate gland, if it is confined to the prostate and if not where has it spread to in the body. Once again this classification helps the doctor assess the best form of treatment and will provide a good idea of the patients chances of survival. It is important to know that this staging is not a precise science. As many as twenty percent of patients are understated. This means their cancer is worse than originally thought. Likewise about ten percent of patients can be over staged. The reasons for this error in staging are multiple. One of the reasons lies with our current technology. Technology has not reached the point of accuracy where in any one patient can the physician state in black and white that their condition is exactly so at this particular point in time. Remember it only needs one cell to escape from the prostate gland and to survive within the host body to change the whole outlook for that patients? survival. At current levels of technology we cannot pick up microscopic disease that has escaped from the prostate gland. The TNM system is used worldwide today to provide information on a patients? staging. Any doctor in the world should now know what a patients? status is even if he does not speak the language of the patients? referring doctor or the patient himself. The TNM system is used to stage all cancers. The system as applied to the prostate gland is shown below.
The T applies to the local extent of the disease.
The N assesses lymph node involvement. The lymphatic system contains your body?s? immune system. This system is monitoring all the time for infections and tumour cells. The lymphatic channels drain tissue fluid bathing the cells of your body and return it to the heart. Along the lymphatic channels lie the lymph glands in chains. Cancer cells easily break off from the parent tumour and drain through the lymphatic system. In the lymph glands these tumour cells are either killed or overwhelm the hosts own defence mechanisms. Involved glands become enlarged and hard. These glands if just below the skin can be felt. Otherwise they may show up on imaging modalities such as CT scans. Lymph gland involvement in prostate cancer is a bad prognostic sign. It is not common for superficial nodes that the patient can feel to be enlarged due to prostate cancer. This is because the prostate is drained by deep pelvic glands hidden from prying fingers. Lastly the M indicates if tumour masses are present in other organs of the body. In prostate cancer the classical organ that the disease spreads to is the skeleton. In particular, the bones of the spine are a favoured site. The first sign of a prostate cancer may be an unexplained back ache.
What Are The Symptoms Of Prostate Cancer?
In most men there are no symptoms until the disease is fairly advanced. Often the tumour has reached the stage where it cannot be cured when the first symptoms manifest themselves. This is the reason why screening for the disease long before symptoms develop came into vogue. See page on SCREENING. Prostate cancer symptoms when they occur can be divided into local and systemic symptoms.
- Discomfort when passing urine. Doctors call this dysuria.
- Discomfort when passing a stool. This is known as tenesmus.
- Haematuria or seeing blood in the urine.
- Haemospermia. This is the sign of blood in the seminal ejaculate.
- Rectal Bleeding.
- Perineal pain. This is a pain between the legs.
- Bladder outlet obstruction symptoms. These symptoms are not so common and are associated more with benign prostatic enlargement, a very common condition in men. Bladder outlet obstruction if it occurs is a very late sign in prostate cancer.
- Malaise. This is a loss of energy and vitality. It can be caused by overwhelming tumour burden or insidious renal failure.
- Symptoms of renal failure. These include fluid overload, hypertension, sallow complexion and tiredness. This is caused by tumour obstructing the tubes connecting the kidneys to the bladder.
- Loss of weight and appetite. These are late symptoms of advanced disease.
- Bone pain. Typically occurring in the spine but it can occur anywhere. Prostate cancer cells have a predilection for bones.
- Sudden paraplegia. Collapse of a spinal vertebrae can lead to spinal cord compression and paralysis
- Ageing is the most common factor.
- Ethnicity: African Americans have the highest rate of prostate cancer in the world. They have a life time risk of clinical disease measured at 30%. This is double the world average. They have a seven percent chance of dying from the disease. The Asian people have the lowest risk with the Koreans, Japanese and Chinese being the least likely to get this cancer. The risk rate for black Africans is unknown. Of concern is that it possibly mirrors the American population but research is required. There are strong cultural taboos in South Africa that make prostate cancer research difficult in South African black people. Much could be gained however from a national prostate cancer campaign in Africa. White Africans in line with other Caucasians have an intermediate risk of developing the disease.
- Geography: This plays a role in disease distribution. For example Swedish men have double the rate of their German counterparts in developing prostate cancer. Factors such as diet, soil characteristics, sun exposure etc. may influence this type of difference. Japanese transplanted into the United States will increase their risk of prostate cancer with each succeeding generation though they do not rise to the levels of the American average. Diet and genetics are felt to account for this observation. Prostate cancer risk rises with increasing distance from the equator. Sunlight is required to form vitamin D. There is of course less sunlight as one approaches the poles. Vitamin D may have a role in preventing prostate cancer.
- Family: A prostate cancer gene has been identified called HPC1. Breast cancer genes may also increase the risk of prostate cancer in male offspring. Nine percent of all prostate cancers are genetically linked. There are as yet no reliable tests to screen for prostate cancer genes. A single first degree family relative with prostate cancer will double a man?s chance of getting clinical prostate cancer. The risk increases to fivefold if two relatives have the disease and it goes up to an incredible ten times the average risk if there are three relatives with the disease. Families with strong genetic prostate cancer histories tend to see the cancer occurring in younger and younger men with succeeding generations. All men with a family history of the disease should start annual prostate cancer screening in their forties.
- The Male Hormones: Testosterone and its more potent metabolite dihydrotestosterone have a significant role in the pathogenesis and growth of prostate cancer. The precise mode of action however remains elusive. Castrated boys and males deficient in the enzyme that converts testosterone to dihydrotestosterone will rarely get prostate cancer. Men with high normal levels of circulating androgens will have an increased risk of developing prostate cancer. Anabolic steroids used by body builders and athletic cheats are a powerful stimulus for prostate cancer as well as kidney and liver cancer. The use of these drugs should be completely outlawed except where medically indicated.
- Sexual Function: A recent Australian study has been the first to show that that regular sexual intercourse or masturbation especially in the twenties and thirties is associated with a decreased incidence of prostate cancer. Prior to this study there were no reports to confirm this statement. Previously the fact that celibate priests had the same incidence of prostate cancer as other men was used as a factor to refute the protective nature of frequent ejaculation. The age of onset of puberty and having a vasectomy has no bearing on prostate cancer occurrence.
- Unhealthy Diets: For more information see the page on prostate cancer prevention.
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