· Prostate cancer is the third commonest cancer death in men after lung and large bowel, with a mortality rate of about 34 per 100,000. For a 50-year-old with a life expectancy of 25 more years, the lifetime risk of microscopic prostate cancer is about 42 per cent, the risk of clinically evident prostate cancer is 10 per cent, and that of fatal prostate cancer is 3 per cent.
· Some 5 per cent of those with prostate cancer have a family history and there is a modestly elevated lifetime risk for male carriers of BRCA1 and BRCA2 mutations.
· Other risk factors include age and black race. In the USA, black men have about a 60 per cent higher incidence rate than white men.
· With no treatment, 15-year disease specific survival ranges from 95 per cent for well differentiated to 30 per cent for poorly differentiated cancers.
· The two screening tools available to GPs are digital rectal examination and prostate specific antigen (PSA) testing. The former is highly user-dependent while the latter is neither very sensitive nor specific.
· The presence of benign prostatic hyperplasia (BPH) and prostatitis can raise PSA levels and thus produce false positive results.
· Only around a quarter of asymptomatic men with an abnormally high PSA will be shown to have prostate cancer on biopsy.
· Biopsy is an uncomfortable procedure with a significant false negative rate.
· The accuracy of the PSA test may be improved by using age-specific cut-off values, the ratio of free to bound PSA, ratio of PSA serum concentration to gland volume, and rates of change in levels over time.
· Although there is an established screening programme for asymptomatic men in the USA, no such programme exists in the UK as to date there is no convincing evidence of any overall benefit.
Management of local disease
· Treatment options include radical prostatectomy, radiotherapy or watchful waiting with monitoring of serial PSA.
· Radical prostatectomy has an overall mortality of 0.5 to 1 per cent, rising to over 2 per cent in men aged 75 and above. Sexual dysfunction occurs in up to 80 per cent, and urinary incontinence requiring pads or clamps in up to 30 per cent.
· Radiotherapy is associated with a 23-32 per cent risk of impotence, 7 per cent risk of permanent urinary incontinence, and a 10 per cent risk of ongoing bowel dysfunction.
· The key decision is which treatment is likely to produce the greatest number of quality years for any given patient this will obviously vary. Treatment of younger patients and older fit men is likely to be aggressive, even if the tumour is well differentiated.
· Pound CR et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999;281:1591-7
Retrospective analysis of a large surgical series in men with clinically localised prostate cancer found that the median time from the increase in PSA concentration to the development of metastatic disease was eight years. Once men developed metastatic disease, the median actuarial time to death was less than five years.
· Brawley OW. Prostate carcinoma incidence and patient mortality. Cancer 1997;80:1857-63
In the USA, population-based studies found that death rates from prostate cancer have declined by only about 1 per 100,000 men since 1992, despite widespread testing for PSA and increased rates of radical prostatectomy and radiotherapy.
· Iversen P et al. Radical prostatectomy versus expectant treatment for early carcinoma of the prostate: 23-year follow-up of a prospective randomised study. Scand J Urol Nephrol Suppl 1995;172(suppl):65-72
Randomised controlled trail of 142 men with clinically localised prostate cancer compared radical prostatectomy and watchful waiting. After a median follow-up of 23 years it found longer survival with prostatectomy butthe difference was not significant (median survival 10.6 years with prostatectomy and eight years with watchful waiting).
· Paulson DF et al and the Uro-oncology Research Group. Radical surgery versus radiotherapy for adenocarcinoma of the prostate. J Urol 1982;128:502-4
Randomised controlled trial of 97 men with clinically localised prostate cancer compared radical prostatectomy and external beam radiation. Men receiving prostatectomy had reduced risk of metastases (9.8 per cent versus 30.4 per cent, relative risk ratio 68 per cent; number needed to treat: five).
· Shipley WU et al. Radiation therapy for clinically localised prostate cancer. A multi-institutional pooled analysis. JAMA 1999;281:1598-1604
Estimated five-year rates of no biochemical recurrence according to pre-treatment PSA concentrations and histological degree of differentiation. Rates ranged from 81 per cent for PSA levels less than 10ng/ml to 29 per cent for levels of 20ng/ml or more and poor differentiation on histology (Gleason score 7-10).
· Wilt T, Brawer M. Prostate cancer: non-metastatic. In: Clinical Evidence 2001;5:620-9
Dr Mark Wallace offers the key evidence on this important exam topic