What Gleason scores are telling us today

It has been known for a while that interpretation of pathological data, and the assignment and assignment of Gleason scores, today has changed from the way that such data were being interpreted 10 to 15 years ago.

A research team at Duke University set out to compare Gleason scores originally assigned in the mid 1990s with current pathologic evaluation of the same prostatectomy slides, and to assess the effect of the change in interpretation on outcome in patients undergoing surgical treatment of prostate cancer.

Tsivian et al. reviewed the records of 204 consecutive patients who underwent a radical prostatectomy for what was shown to be pT2 or pT3 prostate cancer at Duke between 1995 and 1997. Based on the original pathology slides — but with no knowledge of the original Gleason scores — new Gleason scores were reassigned for each of these patients by a single uropathologist in 2008. The two sets of Gleason scores were then compared, and the original and the re-evaluated scores were assessed for predictive potential in survival regression models.

The results of this study showed the following:

  • The distribution of the Gleason scores differed significantly between the original mid 1990s evaluation and the 2008 evaluation, with the average re-evaluated Gleason score being slightly higher than the original one (6.14 vs 6.39, P < 0.001).
  • The patient’s Gleason score was upgraded in 63/204 cases (30.9 percent) and downgraded in 25/204 cases (12.3 percent) at re-evaluation.
  • The original Gleason score was predictive of PSA recurrence, whereas the newly assigned Gleason score was not.
  • Grouping reassigned Gleason scores into risk groups (low < 7, moderate = 7, and high > 7) yielded a better PSA recurrence definition.
  • Survival curves based on the original Gleason scores could not distinguish between moderate- and high-risk groups of patients.
  • Survival curves based on the re-evaluated Gleason scores showed statistically significant differences between all risk groups.

The authors conclude that interpretation of the slides by pathologists has played a significant role in the Gleason score “shift” over the past 15 years. They further state that contemporary Gleason scores are still a useful prognostic factor for PSA recurrence when they are considered as falling into one of the three standard risk categories.

What The “New” Prostate Cancer InfoLink finds somewhat more puzzling is that a single Gleason score value may not be as important today as it was 15 years ago. This seems particularly puzzling since more patients in this study were upgraded from their original Gleason score than were downgraded. One might reasonably expect this to increase the probability that a single Gleason score would be prognostically valuable.

The other thing that would seem to be open to some question in this study is whether, if a different uropathologist had carried out the reassessment process, one would have seen the same result. It has long been known that there is variation in how different pathologists interpret and assign Gleason scores based on their opinions and their experience. No doubt there will be other and similar studies conducted that may address this issue. It would be very interesting to see if the same result was obtained if Duke sent all these slides to a couple of other uropathologists for two more independent assessments.

5 Responses

  1. This makes one wonder if the real issue is the presence of any Gleason grade 4 cancer. Have grade 4 prostate cancer cells undergone an additional mutation that makes them decidedly more dangerous?

    Will Gleason grade 3 eventually go the way of Gleason grades 1 and 2?

    Should we reconsider what Dr. Jonathan Oppenheimer had to say.

  2. The presence or absence of Gleason grade 4 cancer has long been recognized as one of the critical factors in assignment of risk for progression, but it would be very unwise to consider that it might be the only critical risk factor, for a huge variety of reasons.

    And with respect to Oppenheimer’s opinion, please remember that these were patients who had been treated … not just low-risk patients who might or might not need treatment (dependent, for example, on their age and other factors).

  3. Dr. Tsivian has kindly provided me with some off-line comments about the issue of whether different results might have been observed if the same slides had been reviewed by more than one uropathologist.

    The Duke study group did consider this, but they decided that the logistical complexity and the amount of time need to do this were “disproportionate compared to the potential advantages.”

    In addition, although this is not evident from the abstract of the paper, Dr. Tsivian informed me that “we included a contemporary cohort to minimize variability in grading.” Pesumably this information appears in the full report on this study.

    Finally, Dr. Tsivian believeds that, based on the current literature, “it seems that academic uro-pathologists (at least in the US) do not differ much in assigning Gleason scores” today.

  4. It sounds like it is only the Gleason score that is predictive of PSA recurrence. What about the PSA level prior to any treatment.

    Do two cases with identical Gleason scores but with different PSA values (say 5.0 and 15.0) prior to a treatment give the same PSA recurrence probablity ?

    I would think not.

    Fuat INCE

  5. Dear Mr. Ince:

    You are quite correct. Gleason scores are only ONE factor in the initial patient risk assessment. The other really important ones include: PSA level at the time of diagnosis; number of positive biopsy cores out of the total number taken; clinical stage of the cancer; and age of the patient. And we are just beginning to understand the significance of certain genetic and other more detailed fac tors.

    D’Amico and colleagues, some years ago, were able to show that it was possible to accurately categorize patients with localized disease into three risk groups at the time of diagnosis (low risk, intermediate risk, and high risk), based on their Gleason score, their PSA level, and their clinical stage.

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