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      Grading of prostate cancer: a work in progress

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          Abstract

          Grading of prostate cancer has evolved substantially over time, not least because of major changes in diagnostic approach and concomitant shifts from late‐ to early‐stage detection since the adoption of PSA testing from the late 1980s. After the conception of the architecture‐based nine‐tier Gleason grading system more than 50 years ago, several changes were made in order to increase its prognostic impact, to reduce interobserver variation and to improve concordance between prostate needle biopsy and radical prostatectomy grading. This eventually resulted in the current five‐tier grading system, with a much more detailed description of the individual architectural patterns constituting the remaining three Gleason patterns (i.e. grades 3–5). Nevertheless, there is room for improvement. For instance, distinction of common grade 4 subpatterns such as ill‐formed and fused glands from the grade 3 pattern is challenging, blurring the division between low‐risk patients who could be eligible for deferred therapy and those who need curative therapy. The last few years have witnessed the publication of several studies on the prognostic impact of individual architectural subpatterns showing that, in particular, the cribriform pattern exceeded the prognostic impact of other grade 4 subpatterns. This review provides an overview of the changes in prostate cancer grading over time and provides a thorough description of the various Gleason subpatterns, the current evidence of their prognostic impact and areas of contention. Potential practical ways for improvements of the current grading system are also put forward.

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          Most cited references89

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          The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma.

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            Classification of prostatic carcinomas.

            D Gleason (1966)
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              An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011.

              To update the 2007 Partin tables in a contemporary patient population. The study population consisted of 5,629 consecutive men who underwent RP and staging lymphadenectomy at the Johns Hopkins Hospital between January 1, 2006 and July 30, 2011 and met inclusion criteria. Polychotomous logistic regression analysis was used to predict the probability of each pathologic stage category: organ-confined disease (OC), extraprostatic extension (EPE), seminal vesicle involvement (SV+), or lymph node involvement (LN+) based on preoperative criteria. Preoperative variables included biopsy Gleason score (6, 3+4, 4+3, 8, and 9-10), serum PSA (0-2.5, 2.6-4.0, 4.1-6.0, 6.1-10.0, greater than 10.0 ng/mL), and clinical stage (T1c, T2c, and T2b/T2c). Bootstrap re-sampling with 1000 replications was performed to estimate 95% confidence intervals for predicted probabilities of each pathologic state. The median PSA was 4.9 ng/mL, 63% had Gleason 6 disease, and 78% of men had T1c disease. 73% of patients had OC disease, 23% had EPE, 3% had SV+ but not LN+, and 1% had LN+ disease. Compared to the previous Partin nomogram, there was no change in the distribution of pathologic state. The risk of LN+ disease was significantly higher for tumours with biopsy Gleason 9-10 than Gleason 8 (O.R. 3.2, 95% CI 1.3-7.6). The c-indexes for EPE vs. OC, SV+ vs. OC, and LN+ vs. OC were 0.702, 0.853, and 0.917, respectively. Men with biopsy Gleason 4+3 and Gleason 8 had similar predicted probabilities for all pathologic stages. Most men presenting with Gleason 6 disease or Gleason 3+4 disease have <2% risk of harboring LN+ disease and may have lymphadenectomy omitted at RP. The distribution of pathologic stages did not change at our institution between 2000-2005 and 2006-2011. The updated Partin nomogram takes into account the updated Gleason scoring system and may be more accurate for contemporary patients diagnosed with prostate cancer. © 2012 BJU International.
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                Author and article information

                Contributors
                theo.vdkwast@uhn.on.ca
                Journal
                Histopathology
                Histopathology
                10.1111/(ISSN)1365-2559
                HIS
                Histopathology
                John Wiley and Sons Inc. (Hoboken )
                0309-0167
                1365-2559
                18 December 2018
                January 2019
                : 74
                : 1 , Annual Review Issue ( doiID: 10.1111/his.2019.74.issue-1 )
                : 146-160
                Affiliations
                [ 1 ] Department of Pathology Erasmus MC Rotterdam the Netherlands
                [ 2 ] Department of Pathology Laboratory Medicine Program University Health Network Toronto ON Canada
                Author notes
                [*] [* ]Address for correspondence: T van der Kwast, Department of Pathology, Toronto General Hospital, 11th floor, 200 Elizabeth Street, Toronto M5G 2C5, Canada. e‐mail: theo.vdkwast@ 123456uhn.on.ca
                Article
                HIS13767
                10.1111/his.13767
                7380027
                30565302
                617dd280-0dd3-451d-a18e-01605f0a72ec
                © 2018 The Authors. Histopathology Published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 24 August 2018
                : 06 October 2018
                Page count
                Figures: 5, Tables: 1, Pages: 15, Words: 9950
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                January 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.5 mode:remove_FC converted:24.07.2020

                Pathology
                gleason pattern,grading,prognostic biomarker,prostate cancer,tumour architecture
                Pathology
                gleason pattern, grading, prognostic biomarker, prostate cancer, tumour architecture

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