A recommendation to re-think Gleason grading


Jonathon Epstein, MD, at Johns Hopkins is widely considered to be one of the pre-eminent prostate cancer pathologists in the world today, so it is worth listening when he says that the Gleason grading system needs revision.

In a paper by Trock et al. from Dr. Epstein’s laboratory, the authors describe, in detail, their re-evaluation of pathological data from 3,230 men who had a radical prostatectomy at Johns Hopkins between 2000 and 2005. Their primary goal was to obtain a better appreciation of the relationship between the tertiary Gleason component in radical prostatectomy specimens and subsequent biochemical recurrence of prostate cancer. To do this, they defined the tertiary Gleason component as Gleason grade pattern 4 or 5 for patients with a normal Gleason score of 6 and Gleason grade pattern 5 for patients with a normal Gleason score of 7 or 8.

The results of their re-evaluation of the accumulated data show that:

  • The probability of biochemical recurrence of cancers with tertiary Gleason components were nearly all intermediate between those of cancer without a tertiary Gleason component in the same Gleason score category and cancer in the next higher Gleason score category.
  • The exception was that patients with a Gleason score of 4 + 3 = 7 and a tertiary Gleason component of 5 behaved like patients with a Gleason score of 8.
  • The tertiary Gleason component independently predicted recurrence when factoring in radical prostatectomy Gleason score, radical prostatectomy stage, and prostate specific antigen.
  • The magnitude of the impact of the tertiary Gleason component on recurrence did not differ by Gleason score category.

The authors then go on to make suggestions regarding the use of the Gleason scoring system (although they limit their recommendation to pathological use of the modified scoring system, i.e., after a radical prostatectomy). Specifically, they suggest that the new post-surgical options should be as follows:

  • Gleason score of 6, based on primary and secondary Gleason grades of 3, with no sign of a tertiary Gleason component (i.e., Gleason 3 + 3 + 0 = 6)
  • Gleason score of 6.5, based on primary and secondary Gleason grades of 3 together with a tertiary Gleason component of 4 or 5 (i.e., Gleason 3 + 3 + 4/5 = 6.5)
  • Gleason score of 7, based on a primary Gleason grade of 3, a secondary Gleason grade of 4, and no sign of a tertiary Gleason component (i.e., Gleason 3 + 4 + 0 = 7)
  • Gleason score of 7.25, based on a primary Gleason grade of 3, a secondary Gleason grade of 4, together with a tertiary Gleason component of 5 (i.e., Gleason 3 + 4 + 5 = 7.25)
  • Gleason score of 7.5, based on a primary Gleason grade of 4, a secondary Gleason grade of 3, and no sign of a tertiary Gleason component (i.e., Gleason 3 + 4 + 0 = 7.5)
  • Gleason score of 8, based on either a primary Gleason grade of 4, a secondary Gleason grade of 3, together with a tertiary Gleason component of 5 (i.e., Gleason 4 + 3 + 5 = 8) or a primary Gleason grade of 4, a secondary Gleason grade of 4, and no sign of a tertiary Gleason component (i.e., Gleason 4 + 4 + 0 = 8)
  • Gleason score of 9, based on either a primary Gleason grade of 4 and a secondary Gleason grade of 5 (i.e., Gleason 4 + 5 = 9) or a primary Gleason grade of  5 and a secondary Gleason grade of 4 (i.e., Gleason 5 + 4 = 9)
  • Gleason score of 10, based on primary and secondary Gleason grades of 5 (i.e., Gleason 5 + 5 = 10)

They point out that, although the tertiary Gleason component is now often included in pathology reports, it’s use has not yet been routinely incorporated into predictive nomograms, research studies, and patient counseling. It is clear that this group of pathologists believe that it should be!

Interestingly, in another recent paper from the same laboratory, Miyamoto et al. have published data suggesting that patients with truly organ-confined prostate cancer who receive an accurate pathologic evaluation of true Gleason score 6 (with no sign of tertiary Gleason pattern 4 or 5) can be told that their risk of progression after radical prostatectomy is very rare (of the order of 0.4 percent or 4 cases per 1,000). Just click here to read the detailed comments on this paper.

4 Responses

  1. OK. I don’t understand what is being said here: “The probability of biochemical recurrence of cancers with tertiary Gleason components were nearly all intermediate between those of cancer without a tertiary Gleason component in the same Gleason score category and cancer in the next higher Gleason score category. ” Could you please explain?

  2. Chris:

    Basically, what Dr. Epstein and his colleagues are saying is that, in general, if you have Gleason 3 + 3 = 6 disease and a tertiary area of Gleason grade 4 or 5, then your risk of progressive disease is higher than if you had only the Gleason 3 + 3 = 6 disease and no tertiary Gleason grade 4 or 5 , but it is not as high in risk as if you had Gleason 7 disease.

    The same rationale holds true for men who have Gleason 3 + 4 disease and a tertiary of Gleason 5, but not for men who have Gleason 4 + 3 disease and a tertiary of Gleason 5, because they might as well have had Gleason 4 + 4 = 8.

    In other words, a tertiary Gleason grade of 4 or 5 tends to increase your risk upwards towards the next highest standard Gleason score. Does that help?

  3. Yes. I understood the article. That specific text did not make any sense.

  4. Oh. Sorry. … That sentence is just “science speak.” Read enough medical and scientific journals and it starts to make perfect sense, even though there may be simpler ways to say almost exactly the same thing.

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