Prostate cancer is the most common non-dermatological malignancy among British men. Almost 25 000 men were diagnosed with prostate cancer in the UK in 1999 and nearly 10 000 died from the disease in 2001. Prostate cancer is therefore responsible for about 6% of all male cancer deaths. The incidence increases with age; indeed men approaching 80 years have a more than 100-fold increased risk of prostate cancer compared with those approaching 50 years.
Men with suspected or confirmed prostate cancer are offered a wide variety of biochemical, histological and radiological investigations to diagnose, stage and grade the disease. Accurate staging and grading enables the urologist to optimize treatment for the individual patient. This Chapter describes the investigations undertaken during the patient journey associated with prostate cancer.
In most developed countries, the most common mode of presentation of prostate cancer is that of an asymptomatic man with a raised serum prostate-specific antigen (PSA), detected at opportunistic testing. There has been considerable debate about the potential merits of a PSA-based screening programme, but there is little evidence at present to suggest that screening meets the World Health Organization (WHO) criteria for screening. Two large, multicentre trials of prostate cancer screening, based on serum PSA assay and digital rectal examination, and involving more than 100 000 men, are in progress; results are not expected until 2008. Asymptomatic men may also present as a result of diligent use of the digital rectal examination in the primary or secondary care setting; this is the primary means of diagnosing the large number of cancers in men whose serum PSA lies within the age-specific 'normal' range.
Symptomatic men may present with symptoms from either the primary prostate cancer or from metastases. Local symptoms include those of bladder outlet and ureteric obstruction, haemospermia, impotence and reduced ejaculatory volumes. Investigation of lower urinary tract symptoms and erectile dysfunction is discussed elsewhere in this book and will not be discussed further here; it is important, however, that prostate malignancy is not forgotten as a potential cause.
PSA is a 28.5 kDa glycoprotein containing 237 amino acids; the mature protein is cleaved from a 261 amino acid precursor molecule. It is a serine protease belonging to the kallikrein protease family and is also classified as human kallikrein 3 (hK3). Transcription of the PSA gene is under the control of an androgen-responsive element (ARE) within its promoter; expression therefore increases when prostate cells are treated with androgens or become more sensitive to androgens. High-level expression of PSA is exclusive to the prostate epithelium; lower levels of expression are seen in the placenta, some breast carcinomas and the male peri-anal glands.
Healthy prostate glands sequester PSA in an inactive state within the glandular lumina, where it may be activated on cleavage by human kallikrein 2 (hK2). PSA ...