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Refining PSA as a serum marker for diagnosis and for monitoring therapy of prostate cancer patients

PSA is a neutral kinase (34kd molecular weight). It occurs in highest concentration in the lumen of prostatic ducts (1000-10,000 X that in the serum). One physiological function is lyse the seminal coagulum thereby helping sperm motility. Three forms are found in the serum viz. ‘Free’ (average half-life of T1/2 of 1.5 hours), ‘Bound’ (average T1/2= 3 days) and ‘Total’ (average T1/2 = 2.6 days). The majority of PSA in the serum is bound to serum proteins.
 
A number of diseases cause the serum PSA to rise (e.g. cancer, benign prostatic hypertrophy, infection of the prostate and infarction of the prostate). The definition of the normal serum range for PSA is therefore quite difficult to define particularly as benign prostatic hypertrophy is very common – indeed is part of the normal ageing process. However, in general, the rise in PSA in benign prostatic hypertrophy is less than in cancer.
 
Men with a serum/blood PSA of greater than 4 ng/ml are investigated, although in the elderly this figure might be extended up to a figure of 6-7 ng/ml. A number of efforts have been made to try to refine the PSA performance as a diagnostic tool for detecting early prostate cancer. Thus age specific ‘cut-offs’ have been published to try to find the upper end of the normal range for men of different age groups. PSA density (relating the serum value of PSA to the size or volume of the prostate gland – thus, a man with a large prostate tends to have a higher serum value) has been studied to individualise the normal upper range limit of the serum PSA.
 
PSA velocity refers to the speed with which an individual’s serum PSA rises, as this tends to be faster in men harbouring a prostate cancer than in individuals with benign prostate disease. Lastly, the free:total PSA ratio has been found to be useful in patients, as the ratio tends to be low in cancer patients; this has proved to be a useful discriminator in men with a marginally raised serum total PSA.