Low PSA + Gleason 8 to 10 disease predictive of higher risk, worse survival

It has been hypothesized for some time that men diagnosed with a low PSA level (i.e., < 4.0 ng/ml) but a high Gleason score (of 8, 9, or 10) are at elevated risk for more advanced disease and a shorter survival time than some others.

Falchook et al. set out to test this hypothesis, and the results of their study have now been published in Urologic Oncology.

The authors used data from the National Cancer Data Base to conduct a retrospective analysis. Their study included all men in the database diagnosed with adenocarcinoma of the prostate and a Gleason score of 8, 9, or 10 between 2004 and 2007. They divided the patients into four subsets by PSA levels at diagnosis:

  • 0.1 to 3.9 ng/ml
  • 4.0 to 9.9 ng/ml
  • 10.0 to 19.9 ng/ml, and
  • ≥ 20.0 ng/ml

Here are the key study findings:

  • The database included 37,283 eligible patients.
  • Compared to patients with PSA levels of 4.0 to 9.9 ng/ml, those with PSA levels of < 4.0 ng/ml were more likely to present with
    • Clinical stage T3-4 disease (10 vs. 15 percent, P < 0.001)
    • Node-positive disease (2 vs. 4 percent, P < 0.001)
    • Distant metastasis (3 vs. 5 percent, P < 0.001)
  • Among patients treated by radical prostatectomy, lower PSA levels were not associated with
    • Increased likelihood of pathologic stage T3-4 disease
    • Increased likelihood of node-positive disease
  • Six-year overall survival rates were
    • 89.1 percent for men with PSA levels of 0.1 to 3.9 ng/ml treated by radical prostatectomy
    • 75.8 percent for men with PSA levels of 0.1 to 3.9 ng/ml treated by radiation therapy
    • 91.0 percent for men with PSA levels of 4.0 to 9.9 ng/ml treated by radical prostatectomy
    • 81.0 percent for men with PSA levels of 4.0 to 9.9 ng/ml treated by radiation therapy
  • Overall survival rates of men with PSA levels of 0.1 to 3.9 ng/ml were similar to those of men with PSA levels of 10 to 19.9 ng/ml (on multivariate analysis).

Falchook et al. conclude that:

Patients with Gleason 8 to 10 cancer and PSA levels of < 4.0 ng/ml have more aggressive disease than those with PSA levels of 4.0 to 9.9 ng/ml; these low PSA cancers behave more like those [of patients] with PSA levels of 10 to 19.9 ng/ml.

What is not clear, however, is exactly why these men with low PSA levels and high Gleason scores appear to have a biologically different type of prostate cancer than men with more normal PSA levels at diagnosis (in the 4.0 to 9.9 ng/ml range). It has been suggested that this may be a consequence of some type of cellular de-differentiation, but additional research will be needed to help us resolve this question.

4 Responses

  1. This disease is crazy. Reminds me a bit as being like the card game of Hearts where you don’t want the Queen of Spades and you don’t want any hearts (especially the higher value ones) … unless you go for all the hearts, because then you do want the Queen of Spades.

    So if you’re a Gleason 9, you want to have a PSA between 4 and 10. Mine was 4.03 when diagnosed with a G9. …

    Everyone is different, but one observation I have made in my own case is that just because you fall in the Gleason 8/9/10 camp with a low PSA, it does not mean that your prostate cancer is more or less sensitive to hormone therapy. I have a very low PSA, but it seems to respond to hormone therapy and I have been doing IHT for 6 years.

    I would suggest to anyone that has a low PSA and a high Gleason score that you take PSAs with a grain of salt. I would get periodic scans (and possibly use other markers) just to make sure that PSAs aren’t giving you a false sense of security.

  2. Is there not a logical fallacy in this study’s conception? Because 4.0 ng/ml then, as now, was generally set as the “trigger” point in prostate cancer screening, most individuals who did not meet that criterion would not be referred for further testing (normally a needle biopsy). Their prostate cancer, if they had it, would continue to develop undetected until they presented later with, for example, urination problems or DRE indications or bleeding. Then, of course, their cancer would be further in progression than if it had been detected earlier. (Urologists and pathologists knew, all along, that PSA levels never represented a precise measurement of tumor growth.)

    The study results therefore seem to be telling us not very much of anything.

  3. Dear Ken:

    A PSA level of 4 ng/ml hasn’t been a “trigger point” for a biopsy since the mid 1990s, so I don’t think that there is a logical fallacy here at all.

    Now I do understand that there has been vast inconsistency in the primary care community about (a) whether men should get a PSA test at all and (b) who got referred to a urologist for follow-up based on what PSA values and other relevant findings. However, I don’t think that negates the actual findings of the study.

  4. Ken,

    Did you go thru surgery and/or salvage radiation before hormone therapy?

    I just went thru RP surgery with a PSA of 5.7, Gleason of 9, and positive margins, with seminal invasion. … 60 days after surgery my PSA is now elevated at 0.8; in talks with radiation oncologist and considering Hormone treatment therapy as part of salvage radiation.

    I don’t know where to go from here … but critical to success of salvage radiation is the PSA level. My understanding is radiation is most effective with my type of aggressive cancer before PSA is elevated above 2.0.

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