Free PSA: Total PSA

[Stephanopolous]

Hello, currently doing a urology rotation for my surgical elective. I was discussing the use of PSA with my attending and I've been trying to look up the following question:

Why is a high free PSA favorable in the evaluation of possible prostate cancer (what is it about high free PSA that makes this the case)?

I've been reviewing articles and reading our urology textbook (Smith & Tanagho 18e) but so far all that I can come up with is that if the %free PSA is high that means the bound PSA (active) % is low, which overall is consistent with what is found in men WITHOUT prostate cancer. I am deducing that since a prostatic neoplasm is actively producing PSA that it would be producing the form that is found bound to protein, vs the unbound, inactive form.

They suggest a % free PSA >25% is favorable as opposed to less than that. I just want to make sure I'm not missing anything before I discuss this with him again.

I greatly appreciate any insight! Thanks in advance.

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[cpants]

The higher the %free PSA the higher the likelihood that a PSA elevation is benign (ie. due to BPH). It's not really clear to me why this is the case but it is confirmed in multiple studies.

This is helpful information when the total PSA is range 4-10, a common clinical scenario. Total PSA higher than 10 more concerning for CA regardless of free PSA. Total PSA lower than 4, free PSA not validated. There are nice tables out there regarding probability of cancer detection based on free PSA when total is in the 4-10 range. <10% very concerning for malignancy (>50% malignancy on bx). >25% very reassuring (less than 10% risk malignancy on biopsy).

There other subtypes of PSA as well which are the basis for other tests like 4KScore, Prostate Health Index, etc. which can similarly help guide decisions for biopsy.

 

[Stephanopolous]

Thanks so much for your response. I did more research on it and the only reasoning I could find behind it is that the free PSA is metabolically inactive so less likely to be the form found in high amounts in a neoplastic process.