Prostate cancer is the most commonly diagnosed non-skin cancer in developed countries, second only to lung cancer in terms of male cancer deaths. It is a heterogeneous disease and nearly 10,000 men in the UK died from it in 2002.
Incidence is increasing. This appears to be a result of the aging population and the use of prostate-specific antigen (PSA) as a screening tool.
Use of the tumour marker PSA has led to the detection of many more early-stage cancers. However, it has been estimated that anything from 29 per cent to 80 per cent of PSA-screen-detected cancers would, even without treatment, never become symptomatic and this represents a huge overdiagnosis of the disease.
PSA cannot distinguish between indolent slow-growing tumours that pose no risk and those that are dangerous and aggressive.
PSA is organ specific, not tumour specific. It can be raised for other reasons, including benign prostatic hyperplasia, prostate biopsy and ejaculation.
Around 25 per cent of men with a PSA of 4–10ng/ml will be found to have cancer, increasing to 35 per cent with a second round of biopsies. With PSA values of 10–20ng/ml the pickup rate is over 60 per cent.
Up to 20 per cent of patients with prostate cancer do not have elevated levels of PSA and would therefore be overlooked (hence the importance of digital rectal examination as an adjunct to any PSA test).
Prostate cancer is the only human cancer that although curable, often does not need to be cured. The treatment can be more harmful than the disease.
Some prostate cancers develop slowly and may never cause problems (50 per cent of men aged 80 have prostate cancer on autopsy studies, but only 4per cent die of it), however, others evolve rapidly and are fatal within a few years.
Radical treatment is generally not justified for patients with a PSA concentration over 20ng/ml, as the tumour will often extend beyond the prostatic capsule with micro-metastases or lymph node deposits that cannot be detected by current imaging techniques. The Gleason score (grade of tumour) and the life expectancy of the patient also influence the final decision.
There are three main treatments at present — radical prostatectomy, radical radiotherapy and brachytherapy. A fourth treatment, cryosurgery, which is freeze/thawing to destroy tissue, is gaining popularity.
Radical treatment offers the potential for cure, but can also have serious side-effects, including post-operative pain, hospitalisation, radiation proctitis and varying levels of impotence and to lesser extent incontinence.
With active surveillance (watchful waiting), men have to live with the knowledge that they have an untreated cancer which may progress and potentially, if not switched to a radical treatment in time, may be fatal.
3. Prevention and screening
The Prostate Cancer Prevention Trial, involving over 18,000 men, was published in 2003. It investigated whether the use of finasteride, a 5-alpha-reductase inhibitor that prevents the conversion of testosterone to dihydrotestosterone, would prevent prostate cancer. The trial was stopped early at seven years when finasteride achieved a 24.8 per cent reduction in prevalence compared with placebo.
However, we not advocating that all patients should now start taking finasteride. There was a high rate of cancer detection in both groups more in keeping with autopsy study rates than previous screening studies.
There was a greater proportion of poorly differentiated cancers among the finasteride group, suggesting that reducing the number of cancers overall contributes to a greater proportion of higher grade, more aggressive cancers with worse prognosis.
However, further analysis of this study has suggested that the finding of areas of worse Gleason grade merely reflects greater accuracy of sampling from a smaller gland.
At present, PSA testing for prostate cancer does not fulfil Wilson’s criteria for screening. Only a minority of screen-detected cancers spread beyond the gland to cause disease. Curative treatments can have major side-effects.
A recent report found that PSA screening causes overdiagnosis of rates of prostate cancer. In addition, most of the prostate cancers detected via PSA testing in recent years would have presented clinically anyway.
When considering prostate cancer screening there are men who present clinically; men with aggressive, rapidly advancing cancer for whom screening will not improve their outcome; men whose screen-detected disease represents an overdiagnosis who will become subject to unnecessary treatment; and men whose screen-detected disease represents a threat to their life expectancy.
It is this last group who benefit and unfortunately we do not have the means accurately to identify them.
NHS prostate cancer screening
The NHS prostate cancer screening policy recommends that when a patient requests a PSA test, he should be given full information about the advantages and disadvantages of testing.
The NHS will not be inviting men for PSA testing, however, the government policy states that ‘any man considering a PSA test will be given detailed information to enable him to make an informed choice about whether to proceed with a test or not’. This implies that asymptomatic men may have the test if they want.
To add to this confusion, the British Association of Urological Surgeons issued guidelines on the primary care management of lower urinary tract symptoms (LUTS) in 2004. Part of the work up of every patient with LUTS is a PSA test, not to screen for cancer but rather to determine whether a 5-alpha reductase inhibitor is indicated. Once the GP has that PSA result, if it is elevated, they will have a duty to refer that patient on. It seems likely that PSA screening is on the way whether the case for it is proven or not.
Proof of the ability of PSA testing to reduce mortality will be provided by trials currently under way. In the interim, doctors must act on the information that is currently available in the best interests of their patients.