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Clinical implications of changing definitions within the Gleason grading system

Abstract

Remarkably, more than 40 years after the inception of the Gleason grading system, it remains one of the most powerful prognostic predictors in prostate cancer. Gleason's original grading system, however, has undergone significant revision over the years, first by Gleason and his colleagues, and most recently at the 2005 International Society of Urological Pathology Consensus Conference. The consensus conference and subsequent articles proposing further modifications have helped pathologists to adapt the Gleason grading system to current urologic practice in a uniform manner. The changing definitions of Gleason pattern 3 and 4 prostatic adenocarcinoma have tended to narrow the scope of pattern 3 carcinoma and widen the scope of pattern 4 carcinoma. These modifications have had an important role in improving the inter-observer reproducibility of the Gleason system. Whether these changes have a significant impact on the clinical treatment of prostate cancer remains to be seen. However, as many of these modifications are supported only by a few studies, long-term follow-up studies with clinical end points are essential to validate these recommendations.

Key Points

  • After more than 40 years, the Gleason grading system remains one of the most powerful prognostic factors in prostate cancer, partly because it has undergone significant revision over time

  • The most recent revisions to the Gleason system were codified at the 2005 International Society of Urological Pathology Consensus Conference

  • In general, the changes to Gleason patterns 3 and 4 have widened the spectrum of architectural patterns that comprise pattern 4, and narrowed the definition of pattern 3

  • The most immediate result of these changes has been improved inter-observer reproducibility among pathologists and improved correlation between the Gleason scores of needle biopsy and corresponding radical prostatectomy specimens

  • An additional important consequence of the Gleason modifications has been grade migration or upgrading, which makes it increasingly difficult to compare patient outcomes in prostate cancer over time

  • As many recent modifications to the Gleason system are empirical and supported by only a few studies, long-term follow-up studies using clinical end points are necessary to validate these recommendations

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Figure 1: Comparison of the original Gleason and International Society of Urological Pathology (ISUP) 2005 modified systems for pattern 3 and pattern 4 carcinoma.
Figure 2: Cribriform prostatic adenocarcinoma with a slightly irregular edge (arrow).
Figure 3: A central distinction to the 2005 International Society for Urological Pathology modified Gleason grading scheme.
Figure 4: A small cribriform gland that represents pattern 4 carcinoma according to most urologic pathology experts.
Figure 5: A prostatic carcinoma with glomerulations.

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Correspondence to Jonathan I. Epstein.

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Lotan, T., Epstein, J. Clinical implications of changing definitions within the Gleason grading system. Nat Rev Urol 7, 136–142 (2010). https://doi.org/10.1038/nrurol.2010.9

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