T Carcinoma of the prostate has been the most commonly diagnosed male cancer in the United States of America since 1989.
While widely perceived as an indolent disease affecting elderly men, the number of cases being diagnosed in all age groups is increasing. The incidence is highest in the United States, although this may represent in part increased rates of diagnosis in that country, and lowest among Asiatic nations. In Europe, Scandinavian men are at the highest risk although our research suggests a very high risk for black men living in London.
Carcinoma of the prostate has been the most commonly diagnosed male cancer in the United States of America since 1989, with an annual incidence of over 80,000 new cases. In the United Kingdom the reported incidence is lower, with 10,180 cases reported in 1986 and 8098 prostate cancer deaths notified in 1990. In both countries it is now the second most common cause of male cancer death and the incidence appears to be increasing. This increase may be due in part to the confounding factors of an increasing longevity amongst the relevant male population and increased detection rates, but the underlying incidence of the disease also seems to show a true rise. The disease tends to present at an advanced stage unsuitable for radical treatment although screening programmes (both official and unofficial) are diagnosing earlier stage tumours in a number of western countries.
Interestingly, in those communities that have been displaced geographically the incidence of prostatic carcinoma increases in line with the local population's; Japanese men living in the USA have a considerably increased risk compared to their counterparts in Japan.
Parallels between black men in the western world and in Africa are difficult to draw due to the differing life expectancy between the continents.
In the USA black men have the highest risk of prostate cancer of all major racial groups.
It has been suggested that the racial differences mentioned might be related to different serum testosterone or sex hormone binding protein levels between different racial groups, but it is difficult to be sure of this in view of the dietary and geographical differences.
Despite several studies which have suggested that environmental factors may be more important in general than genetic predisposition, no conclusive evidence has proven the link between the disease and diet, sexual behaviour, occupation, pre-existing benign prostatic disease, industrial exposure, vasectomy or pollution.
Environmental factors are nevertheless highly likely to be implicated in view of the migrant studies referred to above with a "Western lifestyle" being an apparent risk factor.
While there is no official screening programme for prostate cancer in this country it is true that many thousands of men are nonetheless being screened for early prostate cancer.
There are two screening methods that may be used in the screening of prostate cancer: digital rectal examination (DRE) and prostate specific antigen (PSA). More and more men are asking for PSA testing now and informed consent is most important since there may be significant implications of an abnormal test.
The diagnosis of prostate cancer can only be reliably made on biopsy. A prostate nodule may be cancer, prostatitis or BPH. As mentioned above, PSA is fallible in the diagnosis of early cancer. Similarly, while many cancers are hypoechoic on ultrasound scanning, 30% are iso- or hyperechoic and not every hypoechoic lesion is a cancer.
In most units biopsy will be done transrectally under ultrasound control using automated fine bore biopsy devices. Using this system and with antibiotic prophylaxis, no anaesthesia is required and the risk of infection is only around two per cent.
Occasionally in very unfit patients with a grossly elevated PSA, anti-cancer treatment might be started empirically, but since a biopsy will give extra prognostic information for little risk it is standard practice to carry one out.
There is no absolute proof that patients treated (or screened) for early prostate cancer have an increased life expectancy. Some studies have suggested that the age-matched survival is equal for untreated and treated patients although none of these has been randomised; it seems unlikely that a properly designed and conducted randomised study will ever be completed.
What we are unable to say today is which prostate cancers will progress to kill the patient and which will be safe to observe. As with many cancers, it may be that a number of potentially lethal tumours will never be amenable to a physical curative therapy. At present no adjuvant or chemical treatment has been shown to be of benefit.
There is similarly no agreement as to whether, if radical treatment is beneficial, radiotherapy or surgery is more effective.
The effect of castration on the size of the prostate has been known about for centuries, but it was in the 1940ís that this became standard practice for men with prostate cancer. IN essence, over 80% of men with metastatic disease will show a dramatic response to hormonal therapy. This may be in the form of surgical or medical castration, or the use of androgen blocking agents. Unfortunately the majority of men will progress, after a mean period of around 15 months.
Until recently there was no consensus as to whether hormonal treatment was best started at the diagnosis or when the patient presented with symptoms. A recent UK MRC study suggests that early treatment of metastatic disease, while not increasing survival, reduces the risk of complications such as spinal cord compression and retention of urine, improving the patientsí quality of life.
Most urologists would therefore recommend early treatment when metastatic disease is diagnosed rather than awaiting symptoms.
Given the choice between surgical castration and medical treatment, most patients will opt for the latter and this is also of interest where operatinglists are at a premium. The first choice for most UK urologists is the use of LHRH ananlgues such as Goserelin (Zoladex) or Leuprorelin (Prostap). Both these drugs work by blocking the stimulatory sites for luteinising hormone in the pituitary, resluting in an aboloition of testicular stimulation and low levels of testosterone. Each is available in one or three month depot preparations.
The question of "Maximal Androgen Blockade" has been acively debated in recent years: associating an antiandrogen and surgical or medical castration has theoretical benefits in terms of reducing to the lowest level possible and allowing minimal androgenic stimlulation by circulating adrenal androgens. Large studies have however faiiled to show a conclusive beneift.
While antiandrogen monotherapy appears equivalent to either LHRH analogue treatment or orchidectomy, the majority of clinicians and patients seem happiest with a depot LHRH analogue injection, largely due to the ease of administration and good compliance that is asssured.
As mentioned above, all men with metastatic disease will suffer from hormone refractory prostate cancer if they survive long enough. This will usually manifest itself by either rising PSA (preclinical), bone pain, ureteric obstruction or anaemia.
While no treatments are curative in this situation, a number of studies are underway to assess new treatments.
No treatment has been shown to be superior for this group of patients in terms of survival, although second line hormonal manipulation may give a dramatic response: I usually use the female sex hormone Di-ethyl stilboestrol (DES) in combination with asprin.
A number of studies are being run in patients with relapsed disease: these are changing frequently and the link to prostate cancer trials (under construction) should be looked at for more information
Thus, while there are new treatments being developed all the time, palliation remains important and for this a multidisciplinary approach involving urologist, GP, Palliative care team and radiotherapist is essential.
It is important for patients to realise that, even though their disease may not be curable, symptom control is usually very effective and that a good team will allow management of even the last stages of prostate cancer in a comfortable and dignified manner.
Copyright (c) 1999-2001 GH Muir. All rights reserved.