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Understanding PSA and Free PSA

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Understanding the Difference between PSA and Free PSA

Many individuals often wonder about the difference between PSA and free PSA tests and whether they need to undergo both. The answer to this question varies depending on your specific circumstances, which is why it generates so much debate and confusion.

PSA and Free PSA

PSA, or prostate-specific antigen, is a protein produced by the cells of the prostate gland. It circulates in the body in two forms: bound to other proteins or on its own. When PSA travels alone, it is referred to as free PSA. The free-PSA test measures the percentage of unbound PSA, while the PSA test measures the total levels of both free and bound PSA in the bloodstream.

Elevated levels of PSA can indicate the presence of prostate cancer, but it can also be caused by other conditions such as an enlarged prostate, prostatitis, or advancing age. Surprisingly, research has shown that approximately 75% of men with elevated PSA levels do not have prostate cancer.

Determining Cancer Risk

Traditionally, physicians perform a biopsy to determine whether a man with elevated PSA levels has prostate cancer or another benign condition. However, in an effort to avoid subjecting everyone to a biopsy, some urologists employ the measurement of free PSA for patients with PSA levels between 4 ng/ml and 10 ng/ml – a range often referred to as the "gray area."

Studies have revealed that men with a total PSA in this gray area and a free PSA greater than 25% are more likely to have a benign condition rather than prostate cancer, making a biopsy unnecessary. On the other hand, if the free PSA is below 10%, it is advisable to proceed with a biopsy as the likelihood of prostate cancer is higher.

In certain cases, individuals may have a PSA level within the normal range, but that doesn't entirely rule out the possibility of cancer. A combination of a low PSA level and a low percentage of free PSA could potentially warrant a biopsy. This is why some doctors opt to order both the PSA and free-PSA tests simultaneously.

While the free-PSA test is not indispensable, its results can influence the decision on whether to proceed with a biopsy when combined with other diagnostic tests. In the future, additional tests may emerge that can help determine whether changes in PSA levels are indicative of cancerous tissue or benign causes.

William H. McDaniel, MD

Dr. Robert H. Shmerling is the former clinical chief of the division of rheumatology at Beth Israel Deaconess Medical Center (BIDMC), and is a current member of the corresponding faculty in medicine at Harvard Medical School.

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