The evolution of Gleason grading of prostate cancer

One of the most important prognostic indicators of prostate cancer is tumour grading and the system that has been accepted worldwide for more than half a century was that developed by Donald Gleason. From the time of the publication of Gleason’s original report, the prognostic significance of Gleason scores (GS) has been confirmed. This system was established in the pre-prostate specific antigen (PSA) era when the diagnosis and management of prostate cancer were quite different from current practice. While Gleason grading fulfilled the role of a powerful prognostic indicator for many years, it became evident that, for the grading system to remain relevant in modern practice, certain modifications were required. The initial changes were made by Dr Gleason himself and in 2005, the International Society of  Urological Pathology (ISUP), introduced significant improvements through a consensus conference attended by 52 International Urological Pathology experts. Since the 2005 ISUP conference Gleason scores 2-5 have effectively been abandoned for needle biopsies and as a consequence the lowest score found on a needle biopsy is now 6. The ISUP, through a further consensus conference in 2014,introduced ISUP grading consisting of 5 grades: Grade 1 (GS 3+3), grade 2 (GS 3+4), grade 3 (GS 4+3), grade 4 (4+4, 3+5, 5+3) and grade 5 (GS 9-10). Other changes introduced were to consider all cribriform cancers and tumours with glomerular patterns as grade 4, and to grade mucinous adenocarcinoma based on the underlying architecture. Given the significant new information in the literature, primarily relating to the prognostic significance of percentage of grade 4, it is likely that ISUP grading will evolve further.