Clinical risk reduction: Prostate cancer

Most sufferers die with it rather than from it – but prostate cancer still poses a significant challenge to clinicians. Here Professor Krishna Sethia explores some of the diagnostic pitfalls

PROSTATE cancer is the commonest tumour in men with over 35,000 new diagnoses and 10,000 deaths each year in the UK. The lifetime risk of a man developing prostate cancer is approximately 20 per cent and this risk is increased significantly if there is a first-degree relative who developed the disease under the age of 70. Despite this, the chance of a man dying of prostate cancer is only 2.8 per cent as the disease is often slow to progress. The majority of patients are elderly at presentation and often have significant comorbidities which result in death before the prostate tumour has escaped control. These facts, combined with uncertainties about the role of radical treatment in many patients with localised disease, create significant problems in advising and managing men with early cancers.

Diagnosis

Over 90 per cent of cases of prostate cancer in the Western world are now diagnosed on account of a raised serum prostate specific antigen (PSA), an abnormal digital rectal examination (DRE) or both.

PSA is a glycoprotein produced only by prostate acinar cells. The serum PSA should be <3.0 ng/ml in men under the age of 60, < 4.0 aged 60-70 and < 6.0-6.5 in men aged over 70. A small rise in PSA may be seen after DRE or ejaculation. A more obvious rise can also occur in conditions other than cancer, most notably benign prostatic hyperplasia (BPH), inflammation and retention.

When there is evidence that a PSA elevation could be due to a benign cause, it is reasonable to repeat the test after 4-6 weeks rather than make an immediate specialist referral. If there are symptoms of prostatitis, a course of antibiotics may be indicated and the PSA should fall rapidly as symptoms improve. If the PSA level does then fall significantly, further monitoring is reasonable for a similar period, but if it has not returned to the normal range within three months the patient should be referred for specialist assessment. It should also be remembered that PSA levels are lowered by approximately 50 per cent in patients on 5α-reductase inhibitors – the threshold for referral of these patients should be correspondingly reduced.

Failure to refer on account of an abnormal PSA level is one of the commonest causes of litigation in men with prostate cancer.

Approximately 20 per cent of men with prostate cancer have a normal PSA but the majority will have an abnormal DRE. Thus although DRE alone is a poor predictor of prostate cancer it is a mandatory part of the assessment if cancer is to be excluded.

It is well-recognised that men can develop significant cancers without symptoms attributable to prostatic enlargement. However, the rapid onset of symptoms of bladder outflow obstruction, concomitant back pain or unexplained weight loss raise the possibility of prostate malignancy. These men should have both a PSA checked and DRE performed and be referred for specialist assessment if any abnormality is found.

Screening

Screening for prostate cancer has been a controversial subject for over 20 years. Current evidence suggests that screening of populations does reduce the death rate from the disease by about 20 per cent but, surprisingly, overall survival is not affected. A major concern is the number of men who may undergo unnecessary investigation or receive treatment for cancers detected by screening which would never have caused them any harm. Recent publications show that for every death prevented, 780 men are screened and between 20 and 30 of these will undergo radical treatment. Apart from the anxiety and risk of significant harm that this creates there is a huge financial cost to the system. Despite this, patients often ask to be screened and although this is not standard policy in the UK it is considered appropriate to share information about the risks and benefits of screening and allow the patient to make his own decision. Useful patient information can be found at: http://www.cancerscreening.nhs.uk/ prostate/prostate-patient-info-sheet.pdf

Investigation and management

In men with a 10-year or greater life expectancy, radical treatment may improve prognosis – it is therefore important that these patients are referred for a specialist opinion under the two-week suspected cancer pathway. Patients with a shorter life- expectancy will usually not benefit from aggressive treatment but with the advent of new treatments, and given a natural degree of patient anxiety, the default position should be to refer these patients similarly. Having said that, there is a group of patients, typically the very elderly and frail, where the only intervention that may or may not be indicated is hormonal manipulation. There is no absolute need to refer these patients to hospital but it is sensible to discuss individual cases with local urologists if there is any doubt.

The diagnosis of prostate cancer is usually made on the basis of a transrectal ultrasound scan and biopsies. Current evidence is that the traditional sextant biopsies miss many tumours and therefore at least 10 biopsies should be taken. Given that this creates a significant risk of systemic infection (and that there is even a very small mortality associated with biopsies as a result) the patient must be fully informed of the risks and the procedure must be covered with appropriate antibiotics. Negative biopsies do not absolutely exclude cancers so under these circumstances it is important that a PSA test is repeated after 3-4 months. If the level remains high further, more extensive biopsies may be indicated. If a patient becomes pyrexial and/or systemically unwell following biopsy they must be aggressively treated with appropriate antibiotics and other supportive measures. If there is any doubt about clinical progress the patient should be admitted to hospital as an emergency.

Whilst there are several available management options for localised prostate cancer there is scant scientific evidence of the superiority of any particular approach. It is therefore essential that the specialist gives a clear explanation both of this full range of management possibilities and of the advantages and risks of specific procedures, which must be explained clearly to patients at all stages of their pathway. Investigation and treatment recommendations should be made by the urological MDT but it is the responsibility of the consultant urologist to ensure that patient preferences have been given due weight in deciding on a particular management plan.

In this context, patient information leaflets can be extremely valuable and their issue should be documented in the clinical notes to support evidence that the patient has been appropriately counselled. Similarly, when treatment is planned it is important that consent is accurately documented and includes precise evidence of the information that the patient has been provided. Given that many treatments carry a significant risk of serious side-effects, it is important to be able to demonstrate that patients have received sound advice if potential litigation is to be successfully defended.

Follow-up

Once a patient has received radical treatment or is established on hormone manipulation, they may (by local agreement) be discharged back to primary care. When this happens it is important that general practitioners have clear instructions about indications for re-referral. These would normally include development of new symptoms or signs possibly attributable to the cancer (e.g. obstructive voiding, bone pain, reduced renal function) or a rise in PSA above a previously agreed value. Rarely a patient may develop difficulty in walking with or without back pain – this is a clinical emergency as it may indicate spinal cord compression and require urgent surgical or oncological intervention if paraplegia is to be avoided.

Professor Krishna Sethia is a consultant urologist and medical director at Norfolk and Norwich University Hospitals and an honorary professor at the University of East Anglia