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International Society of Urological Pathology (ISUP) Grading of Prostate Cancer: Author's Reply.

In Reply: Egevad and colleagues in their letter refer to the new prostate cancer grading system as the 5-tiered ISUP Grading System. However, the new grading system was first described in 2013 at The Johns Hopkins Hospital where I was the senior author and was verified by a large multi-institutional study that I led, both before the 2014 consensus conference. The new system uses the terms Grade Groups 1-5. The data from these 2 studies and the rationale and evidence in support of the new grading system were presented to the attendees of the 2014 conference where 90% voted to accept the new grading system. Although the 2005 and 2014 ISUP consensus conferences, which I both chaired or co-chaired, were instrumental in many of the grade changes that are incorporated within the new grading system, the ISUP conferences did not come up with the concept, nor did they do the research that led to the new 5 Grade Groups grading system. To therefore rename the grading system solely as the ISUP Grading System is misleading and inaccurate. The term ISUP Grade 1-5 conflicts with the paper first describing the new grading system,1 the subsequent multi-institutional verification study, the proceedings from the 2014 ISUP consensus conference published in AJSP in 2016,4 and the 2016 Edition of the World Health Organization of the Pathology and Genetics: Tumours of the Urinary System and Male Genital Organs, all which refer to the new grading system simply as Grade Groups 1-5. Egevad and colleagues claim that this terminology “runs contrary to the decision made by the organizing committee before the 2014 ISUP conference.” As one of the cochairs of the organizing committee, there was no such discussion or decision on this issue before the conference. Egevad and colleagues also criticize the terminology “Grade Groups” as they consider it to be “score-based.” This criticism reflects a lack of understanding of the new grading system, considering it merely as a translation of Gleason scores into new Grade Groups. As noted in the Letter to the Editor relating to the photomontage, because of significant differences in criteria and reporting compared with the Gleason’s original grading system, the current Gleason system is in practice very different from the original Gleason system. To distinguish the new Grade Groups from the various modifications of the Gleason grading system and eventually replace it, the definition of the Grade Groups are based on histologic patterns (Table 1) and are accurate to report as Grades 1-5. Currently, the Grade Groups are used side-by-side with Gleason scores to familiarize users with the new grading system but eventually will be a stand-alone system. Egevad and colleagues complain that the illustrations did not receive the approval of the consensus conference, nor was it discussed with the consensus conference-organizing committee. Nowhere in my Letter to the Editor did I imply in any way that the photomontage had the “imprimatur” of ISUP. Does every opinion or work that is published concerning prostate cancer need to have the formal approval of the ISUP or some consensus committee? Using this logic, I should not have illustrated and graded figures in my book on Gleason grading without ISUP’s official approval of each image’s grade. The same would apply for any other author publishing in the field of prostate cancer. The photomontage was based on the principles of the new grading system and the 2005 and 2014 conferences, reflecting my opinion based on my extensive experience in grading prostate cancer. Egevad and colleagues take issue with the photomontage’s “abandonment of the 2 lowest Gleason patterns.” The photomontage reflects the new grading system and not the Gleason grading system. In the new Grade Group System, there is no distinction between Gleason patterns 1-2 and Gleason pattern 3, with Grade Group 1 defined as “only individual discrete well-formed glands.” The reporting of Gleason scores 2-5 has virtually disappeared from current clinical practice. In Gleason’s original data, Gleason scores 2-5 were seen in 27.9% of cases. Pathologists were rendering a diagnosis of Gleason scores 2-4 in 22% to 24% of cases in the early 1990s compared with 1.6% to 2.4% a decade later.8–10 Helpap et al11 demonstrated that, from 1996 to 2000 to 2005, reported Gleason scores 2-4 decreased from 2.7% to 0% and reported Gleason score 5 decreased from 12.2% to 0.3%. Egevad and colleagues cling to certain outmoded vestiges of the Gleason system rather than embrace the new system in which there is no need to distinguish Gleason patterns 1-3.