An update on Gleason grading system today

A review by Epstein in an upcoming issue of the Journal of Urology gives a detailed perspective on the current use of the Gleason grading system, with specific emphasis on the “removal” of Gleason patterns 1 and 2 in evaluating overall Gleason scores of biopsy samples and the value of “tertiary” Gleason pattern data.

Dr. Epstein, who is one of the acknowledged authorities on the analysis and interpretation of prostate histopathology findings, has provided an excellent overview of the way in which the pathology community is currently advised to report their findings to clinicians. His guidance follows the  recommendations of the International Society of Urological Pathologists, issued in 2005 — which can be found in full on line.

We can summarize the key points of the ISUP concensus as follows:

  • Gleason scores (or sums) of 2-4 should “rarely if ever” be diagnosed on the basis of a needle biopsy (but they can still be diagnosed from “chips” resulting from a transurethral resection of the prostate — a TURP).
  • Some prostate cancers (e.g, those with poorly formed glands) that would originally have been classified as a Gleason  pattern 3 cancer should now be classified as Gleason pattern 4.
  • All “cribriform” prostate cancer should be classified as Gleason pattern 4 disease. (“Cribriform” cancers have a sieve-like appearance, as though they are pierced with a pattern of small holes.)
  • Pathologists should report carefully on the presence of tertiary Gleason pattern 4 and 5 cancers in all specimens (from needle biopsies, TURP “chips,” and radical prostatectomies). However, the value of this information in making clinical decisions is still controversial with respect to tertiary pattern data from radical prostatectomy specimens.

Additional points made by Epstein in this article are as follows:

  • Patients need to be advised and to understand, when told that they have Gleason 6 disease, based on a biopsy or a radical prostatectomy specimen, that to all intents and purposes they have been diagnosed with the lowest grade of prostate cancer.
  • When biopsy cores show differing grades of prostate cancer, the pathologist should report the Gleason patterns for each core individually, and the highest individual Gleason grade should be used in making decisions about treatment — regardless of the percentage of the involvement of that grade overall. (In other words if the patient has one core with Gleason 3 + 3 = 6 disease in 60 percent of the core; a second core showing Gleason 3 + 3 = 6 disease in 48 percent of the core; and a third positive core showing Gleason 3 + 4 = 7 disease in just 5 percent of the core, he should still be managed as though he has Gleason 3 + 4 = 7 disease.)
  • The 2005 ISUP guidelines have led to “disease upgrading.” A report issued in 2006 suggested use of the pre-2005 Gleason recommendations compared to the newer recommendations led to a reduction in Gleason 6 pathology from 48.4 percent in one series of patients to 22.0 percent and an increase in Gleason 7 pathology from 25.5 percent to 67.9 percent. However, a second series suggested that the change was less significant (Gleason 6 going down from 68 percent to 49 percent and Gleason 7 going up from 26 to 39 percent).
  • On the basis of the updated Gleason system, organ-confined, Gleason score 6, margin-negative prostate cancer is “virtually 100 percent curable.”
  • The modified Gleason system appears to better predict progression-free survival after radical prostatectomy than the original Gleason system did.

The Gleason grading system is not a perfect system — for many reasons. Additional modifications to the system can probably be expected in the future. As we have previously reported, for example, Dr. Epstein and his colleagues have already made suggestions about a further modification that would allow for systematic inclusion of data from tertiary Gleason patterns 4 and 5 in  assigning Gleason scores.

One final comment. Readers need to appreciate that just because organ-confined, Gleason score 6, margin-negative prostate cancer is “virtually 100 percent curable,” should not be taken to mean that every patient with Gleason 6 disease needs surgery or radiation or some other form of immediate intervention. Another recent report clearly states that “approximately 40% of patients aged 65 and older who begin active surveillance will die of other causes before their cancer progresses to require definitive treatment.” The “New” Prostate Cancer InfoLink is in little doubt that controversies regarding this issue will continue unabated.

8 Responses

  1. This is extremely comforting news to those of us who are Gleason 6. This is why I had my RP at Johns Hopkins to begin with. I know where I stand in their stats.

  2. I think you are not wrong when you say The “New” Prostate Cancer InfoLink is in little doubt that controversies regarding this issue will continue unabated.

    I see that ASTRO got in quickly on the ICER review saying: However, we are concerned that the Evidence Review Group may have given too much weight to the limited data on AS.

    It is not hard to imagine what the surgeons aka urologists will have to say!!

  3. Mike, – The first of your summary of points of the Epstein Paper is stated inaccurately, YOU State: “Gleason patterns 2-4 should “rarely if ever” be diagnosed on the basis of a needle biopsy (but they can still be diagnosed from “chips” resulting from a transurethral resection of the prostate — a TURP).”

    The CORRECT wording should be Gleason “SCORES” of 2-4, etc., etc.
    (which can be verified by quickly checking the referenced abstract)

    Gleason “patterns” are synonomous with Gleason “GRADES”, which run from 1-5, the Primary and Secondary of which are added together to get the traditional Gleason SCORE, which runs from 2 through 10.

    Correcting this error is important, so that less knowledgeable readers are not unintentionally misled into confusing these terms, that are so important to understanding the meaning of Prostate Cancer (PCa) language.

    While I am at it, for those unfamiliar with the meaning of the term “tertiary”, it represents “the 3rd in a series”. Since traditional Gleason SCORES have represented the SUM of the 2 most prevalent Gleason GRADES or “patterns” present, the tertiary Grade or pattern is the 3rd most prevalent present in the examined tissue.- (aka) az4peaks

  4. Thank you John. I have made the first correction, which you kindly pointed out.

  5. Mike,

    Did these guidelines get adopted in 2005 by most institutions? Is is common practice for pathologists to adopt these guidelines when issued?

  6. Yes and yes — although it may take a little while before the majority of institutions would claim to be fully compliant with this type of new guidance.

  7. Can a Gleason score of 6 subsequently go down if PSA number does?

  8. Dear Monica:

    If prostate cancer is actually present, a Gleason score of 3 + 3 = 6 is now the lowest diagnosable grade of prostate cancer based on a positive biopsy result, so no, the Gleason score cannot actually go down if it was initially a 6. However, it is far from unknown for a small, low-risk, organ-confined tumor to simply die away and vanish over time, leaving the patient with no cancer and (effectively) a Gleason score of zero.

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