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Prostate Cancer Facts
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?
a) Ageing is the most common factor.
b) 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.
c) 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.
d) 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 mans 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
a re 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.
e) 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 increase 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.
f) 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.
g) Unhealthy Diets: For more information see the page on prostate cancer
prevention.
What Is Prostate Cancer?
General Aspects
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 invade 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 becomes more
susceptible to injury and the abnormal cells survive or evade the bodies
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 roll
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 mot 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 world wide 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 bodys’
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.
Local Symptoms
a) Discomfort when passing urine. Doctors call this dysuria.
b) Discomfort when passing a stool. This is known as tenesmus.
c) Haematuria or seeing blood in the urine.
d) Haemospermia. This is the sign of blood in the seminal ejaculate.
e) Rectal Bleeding.
f) Perineal pain. This is a pain between the legs.
g) 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.
Systemic Symptoms
a) Malaise. This is a loss of energy and vitality. It can be caused by
overwhelming tumour burden or insidious renal failure.
b) 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.
c) Loss of weight and appetite. These are late symptoms of advanced
disease.
d) Bone pain. Typically occurring in the spine but it can occur anywhere.
Prostate cancer cells have a predilection for bones.
e) Sudden paraplegia. Collapse of a spinal vertebrae can lead to spinal
cord compression and paralysis
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