In Western countries, prostate cancer is currently the second cause of cancer death in men, and the leading cause of cancer death after the age of 70. These crude data may appear very worrying, but need to be placed in perspective.
The age of onset of prostate cancer is late, during the second part of life, and its frequency increases with age. The population of men over the age of 50 years represents approximately eight people million in France. An estimated 40% of them, i.e. approximately three million, present cancer cells in their prostate.
The potential development of these cells depends on their aggressiveness: in about 20% of these three million men, i.e. six hundred thousand, these cells are sufficiently aggressive to develop. Prostate cancer generally evolves slowly, over a period of more than 10 to 15 years, and remains locally confined, limited to the prostate or its region, for a long time. These figures must be considered in the light of life expectancy which, for a 70-year-old person in France, is estimated to be about 12 years.
These data help to explain epidemiological findings. Although prostate cancer is a major cause of cancer death in elderly men, this mortality remains relatively low, compared to the very large number of latent prostate cancers, as more than 90% of these patients die from other causes.
Finally, it must be kept in mind that, among the two hundred and seventy one thousand men who die each year in France, from all causes, prostate cancer accounts for only nine thousand deaths.
These data, which can be interpreted pessimistically or optimistically, account for the different public health programmes adopted in Western countries.
For example, no screening programme has been set up in Scandinavian countries. Prostate cancer is only treated when it causes symptoms.
On the contrary, in the United States, many screening campaigns have been initiated to allow early diagnosis of prostate cancer, at a stage when there is a chance of curing the patient.
Neither attitude has yet been demonstrated to be superior in terms of prolonging survival, which is why, in France, a consensus conference has recommended only individual screening, adapted to the patient's desires, age and state of health.
Which patients are at particular risk of developing prostate cancer?
The only known predisposing factor is the presence of prostate cancer among the direct ascendants or siblings. Particular surveillance can be proposed in this "high-risk" population from the age of 40 years.
Apart from this particular case, there is no justification for repeated, systematic screening. A prostatic work-up can be recommended in men over the age of 50 years, in good health, who request this screening; when no abnormality is detected, regular evaluation can then be proposed until the age of 75. Over this age, surveillance is no longer justified, as if it has been normal up until then, the risk of developing and suffering from prostate cancer in the future becomes virtually nil.
How to rapidly suggest the diagnosis?
Two examinations are useful:
It is a protein secreted by glands of the prostate. Part of the PSA enters the blood where it can be assayed by taking a venous blood sample. Total PSA and the free PSA circulating in the blood are assayed.
How is the PSA level determined?
Several assay methods are available, which means that PSA levels must be interpreted very cautiously. Most assays indicate a normal value of 4 or less than 4 ng/ml, but others have a normal value of 2.5 or even lower; much more rarely, the normal value is 5 ng/ml. This disparity of measurements makes it very difficult to compare two successive assays performed in two different laboratories, which is why it is important to perform PSA assays in the same laboratory or at least using the same technique. It must be remembered that an isolated moderately raised PSA level (4 to 10 ng/ml) does not have any significance, as the PSA level rises regularly with age and increasing volume of the prostate, even in the absence of cancer. The free PSA level is expressed as a percentage of the total PSA and a low free PSA (less than 12%) may indicate the need for prostatic biopsies.
What is the use of this assay?
All diseases of the prostate can increase the PSA level: cancer, benign prostatic hyperplasia, acute infection of the prostate (prostatitis). Some prostatic procedures, such as cystoscopy or bladder fibroscopy, prostatic needle biopsies, can also increase the PSA level. However, despite a commonly held belief, digital rectal examination does not significantly increase the PSA level (at the very most, it increases PSA by 0.1 to 0.4 ng/ml, which is considered to be negligible).
At what age should it be performed?
Based on the acquired scientific data, the general rule at the present time is to perform PSA assay over the age of 50 years and then annually until the age of 75 years. In men with a family history of prostate cancer (at least two members of the family), PSA assay can be proposed from the age of 40 years.
PSA assays are of doubtful value after the age of 75 years, as the frequency of cancer is very high at this age, but fortunately the vast majority of prostate cancers in elderly men are very small tumours with little risk of progression. Attempts to detect these cancers exposes the patient to all of the anxiety of the diagnosis, when, very probably, no really useful treatment will be proposed, except of course if the patient presents with symptoms.
In practice
When a first PSA assay reveals a level slightly above the normal limit, it must first be ensured that the patient has not undergone any prostatic manipulation or acute infection during the previous two months. Another PSA assay should be performed a fortnight later. If the PSA level is still raised, the physician will decide whether or not the patient should be referred to an urologist. If the PSA level on the 2nd assay remains abnormally raised, it may be useful to perform prostatic biopsies looking for cancer.
Caution: Finasteride (Chibroproscar), used in the treatment of benign prostatic hyperplasia, can decrease the PSA level by about 50%.
PSA after treatment
Prostate specific antigen is one of the elements of surveillance of prostate cancer. After radical prostatectomy, the PSA must fall to a level of 0.1 ng/ml or less. Annual PSA assay is then sufficient.
The minimal PSA level which must be achieved after radiation therapy has not yet been clearly defined. After hormonal treatment, the PSA level falls to low values, varying from patient to patient, over 1 to 3 months. A rise in PSA after treatment by radical surgery or radiotherapy indicates the presence of local recurrence of the disease or the development of metastases, even in the absence of any symptoms. Note that:
Conclusion
Prostate specific antigen (PSA) levels must be interpreted cautiously they are only moderately raised. Biopsies are never urgent and it is preferable to repeat the PSA assay when it is only slightly above normal because individual variations of PSA levels are frequent.
The course of treated prostate cancer can be followed by monitoring PSA levels, bearing in mind that it is useless to repeat this assay month after month. Intervals of several months are necessary to accurately evaluate the course of PSA levels.
Finally, PSA levels are not the sole indicator of prostate cancer. Medical decisions are based on a whole series of factors and not simply on the results of a laboratory test.
The final proof of the presence of a cancer can only be obtained by analysing the prostatic tissue.
In the presence of highly suggestive elements, the urologist will perform biopsies of the prostate. This examination, performed as an outpatient procedure, without anaesthesia, consists of taking several very fine cylinders of prostatic tissue through the rectum, by controlling the site of the various samples by prostatic ultrasonography. These biopsies are performed using a biopsy gun which makes the operation virtually painless. Antibiotics are prescribed to decrease the risk of prostatic infection (3% of cases).
Microscopic examination of the fragments obtained then confirms or excludes the diagnosis of prostate cancer. In the presence of cancer cells, this examination also provides essential information about the aggressive potential of these cells, by assessing the volume of the cancer and the extent of cancer cell changes compared to normal prostatic cells.
Only when all of this information is available, possibly completed by specialised radiographic examinations (CT scan, bone scan, MRI), can the urologist propose a treatment plan adapted to the patient and his disease, case by case, taking into account the patient's personal desires, age and general state of health, as well as the criteria of aggressive potential of the tumour.
a-Radiological examinations
What is the role of ultrasonography in the diagnosis of localised prostate cancer?
Transabdominal ultrasonography is unable to correctly visualise the prostate. Transrectal ultrasonography is more precise, and allows good visualisation of the contours of the prostate. So-called hypoechoic zones in the prostate, when they are isolated, i.e. with no abnormality on digital rectal examination and no elevation of PSA, must not be considered to be suspicious zones. So-called hyperechoic zones do not have any diagnostic value.
Conclusion
Transrectal ultrasonography cannot be considered to be a primary element of the diagnosis, with the same value as digital rectal examination or PSA assay. The main value of ultrasonography is to allow well targeted prostatic biopsies.
This examination allows detection of iliac and obturator lymph nodes when they are very large. We usually only perform CT scan when the PSA level is greater than 20 ng/ml.
Transabdominal magnetic resonance imaging (MRI) provides the same information as CT scan. The results of transrectal MRI have not yet been validated.
Bone scan is a radiological examination which allows detection of bone metastases, i.e. secondary sites of a cancer in bone. Prostate cancer can induce this type of metastasis. The technique is simple. It consists of injecting a radioactive substance into a vein, which is then selectively taken up by bone. Three to 4 hours after the intravenous injection, the patient is placed under a camera gamma which takes a photograph of the whole body and reveals zones of uptake of the radioactive substance.
This examination is not painful, but simply long. There are no known serious complications. The images may be difficult to interpret, as the radioactive substance is not exclusively taken up by zones containing cancer cells. Most bone diseases, such as osteoarthritis, sequelae of trauma, inflammatory joint diseases, etc. also take up the radioactive substance. Bone scans must therefore be interpreted cautiously, especially in the presence of only a few sites of uptake. The examination can be safely repeated.
b-Prostate biopsies
Routine digital rectal examination in men over the age of fifty and the development of PSA (prostate specific antigen) assays facilitates the detection of prostate cancers at an earlier stage than previously, but only biopsies can confirm the presence or absence of prostate cancer by taking small pieces of the gland for examination under the microscope.
As the ultrasound probe is inserted into the rectum, a short course of antibiotics is recommended, but it is not essential to perform an enema.
Biopsies are performed as an outpatient procedure without anaesthesia. The patient is placed on the left side, with the thighs flexed onto the stomach. The urologist performs digital rectal examination, then inserts the ultrasound probe into the rectum. He locates the prostate on the ultrasound screen and uses a small ultrarapid biopsy gun, fitted with a very fine needle, to perform six biopsies from various parts of the prostate: one in the upper part of the prostate, called "base", another in the middle part of the prostate called "median" and one in the lower part of the prostate, called "apex", on the left and right sides. Biopsies of the seminal vesicles, which drain into the prostate gland, may also be performed. These biopsies last several minutes and are not painful. A survey conducted in 100 men undergoing prostatic biopsies showed that only two of them would have preferred an anaesthetic. In all other cases, the men interviewed said that they easily tolerated the biopsy and would be ready to undergo another biopsy, if necessary. Over the hours and days following the biopsy, a small amount of blood may be emitted from the rectum (rectal bleeding), urethra (urethral bleeding) or in the semen (haemospermia). These signs are not at all serious and resolve spontaneously without treatment.
There is a real risk of prostatic infection after biopsies, which is why antibiotics are administered before and after prostatic biopsies. 2 to 3% of cases nevertheless develop fever during the hours or days following biopsies, despite antibiotics. This fever is usually high (39 - 40°C) with rigors, resembling influenza. In such cases, the physician or urologist may decide to change the antibiotics.
Men taking anticoagulants or aspirin for cardiovascular disease must stop their treatment before prostatic biopsies to avoid the risk of haematoma.
They have a twofold value:
1. They confirm the presence or absence of cancer cells in the prostate.
2. By analysing the number of positive biopsies among the total number of biopsies performed, and by analysing the appearance of the cancer cells obtained, it is possible to fairly precisely determine whether the cancer is confined to the prostate or whether it has already extended beyond the capsule of the prostate. This information is important to determine the most appropriate treatment for the disease.
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