What is Prostate Specific Antigen (PSA)?
Prostate Specific Antigen (PSA) is a protein enzyme produced by the cells within the prostate gland and secreted into seminal fluid. During intercourse the sperm from the testicles, seminal fluid from the prostate and a gel-like secretion from the seminal vesicals is secreted into the part of the urethra inside the prostate. This material forms semen and is ejaculated during sexual climax. PSA is intended to be in the prostate seminal fluid and is therefore found in the blood in very small concentrations. There is no normal mechanism for PSA to get into the blood. Diseases of the prostate that alter the relationship between the glands and the blood vessels allow more PSA to be absorbed into circulation. There has been much research on the topic of what is a 'normal' PSA blood concentration and at what PSA blood concentration should trigger an evaluation of the prostate. Initially a concentration of less than 4.0ng/ml was considered to be normal. Then the concept of 'age-adjusted PSA ranges' was put forth as the prostate changes with age. The effects of aging are thought to result in higher levels of PSA in the blood in the absence of prostate cancer. Following a large observational study of PSA over many years followed by prostate biopsy of all observed men, much was learned about PSA. The most recent studies have produced compelling data to support a more complicated approach to evaluating PSA as it relates to a man’s risk of having prostate cancer. In general, the lower PSA the better, with no real threshold for 'normal,' although a baseline PSA should be less than 2.5ng/ml. Men with small prostates in their 40’s should have a PSA under 1.0 – 1.5. Older men with larger prostates can have higher PSA levels in the absence of cancer.
Free and total PSA:
PSA is present in the blood in two most common forms; 1) free, and 2) bound or complexed to another large protein. The amount of 'free' PSA can be measured as can the amount that is 'complexed' to another protein. There is an inverse correlation between the percent of PSA that is 'free' and the risk of having prostate cancer if the total PSA is between 3 and 10. For example, if your total PSA is 4.0 ng/ml and the percent free PSA (also referred to as the free-to-total PSA) is 8% you have a higher risk of having prostate cancer than if the percent free PSA is 28%. The free/total PSA ratio is helpful in deciding which men to re-biopsy after an initial benign biopsy presenting with a persistently elevated PSA. Free/total PSA ratios are not generally used in screening. Men with a normal, small prostate should have a very low PSA. Prostate inflammation, enlargement, recent surgery and cancer can cause the blood PSA to be increased. If the PSA or prostate exam is abnormal, further evaluation with prostate ultrasound and biopsy is recommended.
PSA velocity is a measure of the rate of rise of the PSA over time. For total PSA over 4, an annual increase of more than 0.75ng/ml and for a PSA less than 4, an annual increase of 0.4ng/ml is considered too much. Rapid rates of increase for PSAs in the 0 – 2.5 range are the most sensitive tool for early detection of prostate cancer. If the PSA is low and is rising, a rate of rise more than about 10 – 20%/year is too fast and evaluation should be considered. Men found to have prostate cancer with sudden increases in this range have the highest chance for cure when treated with radical prostatectomy.
Early Detection of Prostate Cancer:
The goal of early detection of prostate cancer is to find curable cancers in men with a significant life expectancy to benefit from treatment of prostate cancer. Annual PSA testing and digital rectal examination (DRE) has improved the ability to detect early, organ confined prostate cancer. Once a prostate cancer is diagnosed, many issues are taken into consideration before deciding on a management plan. See clinically localized prostate cancer for details of the management of newly diagnosed prostate cancer.