The free PSA test in prostate cancer risk assessment: an update

The potential of the percentage of free (unbound) PSA to total PSA  (usually abbreviated to %fPSA) as a measure to assist in the analysis of risk for prostate cancer has been known for years. However, researchers at the Cleveland Clinic thought it might be a good idea to check on that potential in an era of 10- and 12-core biopsies (compared the sextant biopsies customary in the early to mid 1990s).

Lee et al. have assessed data from 1,077 men who had had their %fPSA measured (as well as their total serum PSA) and who had undergone an initial extended prostate biopsy.

The men were divided into two groups based on their total serum PSA levels:

  • Group A was made up of the men with a total serum PSA level >4.0 ng/ml.
  • Group B included only men with a total PSA level ≤ 4.0 ng/ml.

The results of the analysis showed that:

  • Cancer was detected in 453/1,077 patients (42.1 percent).
  • The average (mean) PSA level among all patients was 7.6 ng/ml.
  • The average (mean) %fPSA was 18.0 percent.
  • The ability of %fPSA to predict prostate cancer on initial extended biopsy was significantly better in Group B than in Group A.
  • For men in Group B, a %fPSA level of 11 percent or less was 85 percent specific for a positive biopsy result.
  • For men in Group A, a %fPSA level of 10 percent or less was 85 percent specific for a positive biopsy result.

Lee et al. conclude that the performance of %fPSA in predicting the presence of prostate cancer is not altered when an extended biopsy scheme was used compared to the older sextant biopsy. They are careful to note that a %fPSA level higher than 10 or 11 percent can not be used to rule out the possibility of a biopsy result that is positive for prostate cancer. However, they also note that a low %fPSA value is likely to be particularly useful in predicting prostate cancer — especially in men who may have a PSA level < 4 ng/ml and no indication of potentially cancerous tissue on digital rectal examination.

22 Responses

  1. My free PSA was 8% with a total PSA of 3.6. I had 11/12 positive cores with a Gleason score 7. Post-RALP my patologic stage was T3N0.

    It shows the importance of free PSA when the total PSA is below 4 ng/ml.

  2. PSA 3.66; free PSA 0.79 … 21.6% … 78 years old … diagnosed with severe BPH last month. What does it say?

    J. Chamberlain

  3. Dear Jack:

    It appears to suggest that you have severe BPH, as diagnosed.

  4. My father has a %free PSA of 11 and regular PSA of 5.5 ng/ml. Any insight on translating these results? Biopsy is scheduled because his doctor said he was in the higher risk category (he’s 66) but did not differentiate on whether it was for BPH or cancer.

  5. Dear Jennifer:

    The combination of a relatively low %free PSA and a total PSA > 5 ng/ml does suggest that your father may have some cancer in his prostate … but then so do most men of 66 years of age. If he does have cancer in his prostate, the real question is going to be whether this is clinically significant and is going to cause him any problems later in life. The biopsy will help him to decide this.

    However, when he gets the biopsy result (which could also show no sign of cancer at all), you would be wise to try to persuade him to get some good advice before he decides to “do something” about it — if the result is positive for cancer. Many men of your father’s age are diagnosed with low-risk prostate cancer that can be monitored safely for years and may never need treatment at all.

  6. Hi.

    Thank you so much for taking questions. The relationship between prostate cancer and PSA/%Free PSA is extremely confusing.

    My 50-year-old husband has had two MRI-guided biopsies (1 year apart). He just had another blood test. His PSA is 6.2 and his %Free PSA is 16%. His PSA has been as high as 8.1 ng/ml — but his %Free PSA has never been as low as 16%. Would you please tell me what this may mean with regards to his chance of having cancer?

  7. Dear Francine:

    I am not sure that anyone can tell you and your husband with any degree of certainty what his %Free PSA data “mean” in relation to his risk for prostate cancer. The only two things we know for certain based on what you have written above are:

    (1) His PSA is higher than it really should be for a 50-year-old in otherwise normal health.
    (2) Two sophisticated biopsies (MRI guided) have found no sign of cancer.
    (3) His latest %Free PSA level is lower than one might like it to be.

    However, none of these things, taken alone or together, give one any degree of certainty about your husband’s personal risk for prostate cancer.

    The fact that the two biopsies have both been negative is suggestive that the changes in his PSA over time might be caused by something other than cancer, e.g., a urinary tract infection, chronic prostatic inflammation (a specific form of prostatitis), or a combination of one or both of these with some benign prostatic hyperplasia (BPH).

    He needs to talk to his doctors, but I (just an educated layman) would not encourage another biopsy at this time unless there is some much more concrete evidence of an increased risk for aggresssive disease.

  8. Don’t know if sitemaster is still active.

    White male 62 years old. PSA > 6 for 6 years; up-and-down pattern with very marked increase over that period. Negative biopsy in 2008. I have an enlarged prostate. My PSA jumped from 6 to 12 over a 12-month period (March 2011 to March 2012).

    After 2.5 months on finasteride, Flowmax and antibiotic therapy, the urologist ordered PSA and fPSA tests this week. PSA down to 9; fPSA 9 (first time assay on latter).

    They are very concerned and want me to have another biopsy. I am not concerned about garden-variety prostate cancer, but I’m wondering if the fPSA is correlated with more aggressive cancer. All sources I have seen online and in library, say 85-95% probability that I have some form of cancer, but that the ratio of non-fatal to aggressive forms is basically 80/20.

    All sources say straight-forwardly that biopsy is in order. I’m under VA care, which has been very good.

    What do you think?

  9. Rob:

    It would be easier to discuss this in more detail if you joined our social network. However:

    (1) In principle I think a biopsy is in order. There is no way to differentiate between risk for aggressive and indolent forms of prostate cancer without a biopsy, and you still may not have prostate cancer at all. Neither the PSA test nor the fPSA test are prostate cancer specific tests.

    (2) Depending on the results of the rebiopsy, you would be in a better position to make decisions about any need for treatment, which is a quite separate issue.

  10. Jeff B. 53 yr old male. PSA (total) tests yearly through 2010 … all levels <0.8. PSA test in April 2012 … total PSA of 4.8. PSA test in July 2012 … total PSA 3.7, %Free PSA 11%.

    Would appreciate your thoughts and whether a biopsy is warranted. Also — any real risks associated with a biopsy. Will be seeing urologist next week.


  11. Jeff:

    It would be best if you joined our social network, which was designed for this sort of discussion, but basically “Yes, at your age a biopsy would be wise.” The biggest risk is from the chance of infection, which can be best avoided by asking your urologist to give you a rectal swab and get it cultured, just in case you carry unusual organisms (bacteria) that are less responsive to the normal antibiotics used for prophylaxis prior to a biopsy.

  12. I am 66 years of age and have had four biopsies over the past 10 years. Previously, I was diagnosed with PIN with a PSA level of 5.2; no medication or other treatment was prescribed. Another recent blood test reflected a PSA of 6.10 and a %free PSA of 16%. Should I have another biopsy? What are the statistics of a standard 12-sample biopsy showing something other than PIN for my age group?

  13. Dear Bill:

    For men in their mid-60s as a whole, the chances of a finding of some prostate cancer (clinically significant or not) if they have a second biopsy after a prior finding of PIN are fairly high, but the real issue here is not “men in your age group.” The real issue is your personal risk.

    With a small increase in your PSA, and with a prior diagnosis of PIN, the chances of you having clinically significant prostate cancer (i.e., a cancer that would ever affect you in your remaining lifetime) would seem to be very small — after your four previous negative biopsies. However, you should really discuss this with your doctors.

  14. I am 50 years of age and recently started treatment. Before treatment my PSA was 4.1 and my free PSA was 20%. After 6 months on treatment my PSA is 4.8 and my free PSA is 16%. Would treatment cause this shift? Thanks.

  15. Dear Brad:

    We would need a lot more information to answer this question, and we normally do this through our social network where we can do this without exposing all your clinical data to public scrutiny. So … If you would join our social network and add relevant data there (including HOW you are being treated), we will see what we can do to be of assistance.

  16. After reading these comments and the remarkably clear, concise, and accurate replies, one important issue that occurs to me is that it is not only the biopsy and quality that is important but, perhaps more importantly, the quality of the pathology report. I feel that most patients should have two quality readings, for while pathologists all like to think they are right, their readings are as much an art as a science, and there are a wide array of “artists” out there. Additionally, patients should always have copies of these seminal reports, and the descriptive notations should be detailed (percent of cancer in each core, length of core, Gleason scores and variations among scores, other tumor markers, and so forth). My experience as a clinician is that few pathologists are ever this detailed. Patients should seek recommendations for a second, referral of their biopsy slides to a source noted for his/her high quality interpretations.

    [PCa since 2004, Gleason 4,5, initial PSA 32.52, PSA < 0.01 since late 2005 after therapies.]

  17. Hello,

    Please advise. My father is 69 years old, %Free PSA is 13%; free PSA is 0.16 ng/ml; total PSA is 1.25 ng/ml. He was also taking a herbal mix for the past 2 years — but stopped taking it 10 days before doing the test. Please advise whether he needs to do BPH and whether there are any tests that he needs to do.

    Thank you,

  18. Dear Nesreen:

    Although your father’s %free PSA is relatively low, I can see no specific reason from the data that you have provided why he would need to do anything at all if he is otherwise healthy. However, you have given us very little information to go on. Is he healthy? How old is he? Does he have any signs, symptoms, or history of lower urinary tract problems? What has his doctor said to him?

    If you want to continue this conversation, it would be best if you could join our social network so that we could continue it there rather than here.

  19. I am a white man of age 65. In January 2012 I had my PSA tested for the first time and it was 4.2. My %free PSA at thatb time is unknown to me. I was seen by a urologist and he told that my prostate is moderately enlarged but smooth and he did not see any problem. Next PSA was in August 2013 and it was 7.7 and my %free PSA was 12%. I went to another urologist who told me that my prostate was enlarged, smooth but it was not symmetric. A PCA3 urine test was taken in the office; additionally, he recommended that I have an MRI of the pelvis with and without contrast and then he will make a decision about biopsy. I want to know if, according to what we know now, I have a big chance to have a prostate cancer?

    Thank you!

  20. Dear Joseph:

    Based on the information that you have provided above, if we assume that your rectal exam is classified as “abnormal” because of the shape of your prostate, the PCPT risk calculator projects that you have a 15% chance of high-grade prostate cancer, a 19% chance of low-grade cancer, and a 66% chance that the biopsy is negative for cancer.

    If we assume that your prostate cancer is actually “normal” (as opposed to “abnormal”) because the rectal exam is a highly opinion-based diagnostic procedure (unless there is very significant evidence of abnormality), then your risk goes down to a 10% chance of high-grade prostate cancer, a 21% chance of low-grade cancer, and a 69% chance that the biopsy is negative for cancer.

  21. My husband (age 65) has a family history of prostrate cancer: his father and his brother, as well as his mother’s brother. His numbers are below and what does this mean — especially knowing his family history? He has a tendency to ignore test results. which is the reason for my inquiry.

    Thank you

    Free PSA 1.0
    Total PSA 4.3
    %Free PSA 23

  22. Dear Paula:

    All that I can tell you is that your husband does have a significant level of risk for a diagnosis of prostate cancer based on his family history and his recent PSA level of 4.3 ng/ml. It is utterly impossible to tell you any more than that without further tests being carried out.

    Things that might be very relevant include whether he is also showing signs of an enlarged prostate (benign prostatic hyperplasia) and the precise nature of the forms of prostate cancer identified in the three relatives you mention. It is possible that — even though your husband is at an above-average risk for prostate cancer — it is a risk for clinically insignificant (as opposed to clinically serious) prostate cancer.

    There are several possible tests that could be given to your husband to determine whether it would be a good idea for his to have a prostate biopsy. These include things like the Prostate Health Index or phi test and the 4KScore test as well as germline DNA testing and others.

    However, if I was your husband, I would go and see a prostate cancer specialist at a major academic medical center to discuss my risk level and what I could do about it (if that is easily possible).

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