The new ISUP 2014/WHO 2016 prostate cancer grade group system: first résumé 5 years after introduction and systemic review of the literature



To systematically and comprehensively review and summarize the most recent literature assessing the value of the new grading system introduced by the International Society of Urological Pathology (ISUP) in 2014 and accepted by the World Health Organization (WHO) in 2016.


A systematic literature search in the PubMed database was performed up to November 2018. Overall, 15 studies in the period from 2016 to 2018 evaluating the new grading system have been selected for evidence synthesis.


The main goals of the new ISUP 2014/WHO 2016 grading system were to establish (I) a more accurate and simplified grade stratification, (II) less overtreatment of indolent prostate cancer as well as (III) an improved patient communication. The majority of the studies chose biochemical recurrence as an endpoint for evaluation and statistically assigns the new ISUP 2014/WHO 2016 grading system a higher prognostic accuracy than the former Gleason grading. However, in only a subset of studies it was clearly evident that the historical samples were not only re-grouped according to the new grade groups but also re-graded according to the new histomorphological 2014 ISUP criteria.


The vast majority of the studies support an improved prognostic accuracy of the ISUP 2014/WHO 2016 grade groups and endorse its worldwide application.

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  1. 1.

    Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, Fossati N, Gross T, Henry AM, Joniau S, Lam TB, Mason MD, Matveev VB, Moldovan PC, van den Bergh RCN, Van den Broeck T, van der Poel HG, van der Kwast TH, Rouviere O, Schoots IG, Wiegel T, Cornford P (2017) EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol 71(4):618–629.

    Article  PubMed  Google Scholar 

  2. 2.

    Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, Henry AM, Joniau S, Lam TB, Mason MD, van der Poel HG, van der Kwast TH, Rouviere O, Wiegel T, Mottet N (2017) EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol 71(4):630–642.

    Article  PubMed  Google Scholar 

  3. 3.

    Montironi R, Cheng L, Lopez-Beltran A, Scarpelli M, Mazzucchelli R, Mikuz G, Kirkali Z, Montorsi F (2010) Original Gleason system versus 2005 ISUP modified Gleason system: the importance of indicating which system is used in the patient’s pathology and clinical reports. Eur Urol 58(3):369–373.

    Article  PubMed  Google Scholar 

  4. 4.

    Brookman-May S, May M, Wieland WF, Lebentrau S, Gunia S, Koch S, Gilfrich C, Roigas J, Hoschke B, Burger M (2012) Should we abstain from Gleason score 2-4 in the diagnosis of prostate cancer? Results of a German multicentre study. World J Urol 30(1):97–103.

    Article  PubMed  Google Scholar 

  5. 5.

    Epstein JI, Amin MB, Reuter VE, Humphrey PA (2017) Contemporary gleason grading of prostatic carcinoma: an update with discussion on practical issues to implement the 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol 41(4):e1–e7.

    Article  PubMed  Google Scholar 

  6. 6.

    Pierorazio PM, Walsh PC, Partin AW, Epstein JI (2013) Prognostic Gleason grade grouping: data based on the modified Gleason scoring system. BJU Int 111(5):753–760.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE (2016) The 2016 WHO classification of tumours of the urinary system and male genital organs—part B: prostate and bladder tumours. Eur Urol 70(1):106–119.

    Article  PubMed  Google Scholar 

  8. 8.

    Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097.

    Article  Google Scholar 

  9. 9.

    Offermann A, Hohensteiner S, Kuempers C, Ribbat-Idel J, Schneider F, Becker F, Hupe MC, Duensing S, Merseburger AS, Kirfel J, Reischl M, Lubczyk V, Kuefer R, Perner S (2017) Prognostic value of the new prostate cancer international society of urological pathology grade groups. Front Med 4:157.

    Article  Google Scholar 

  10. 10.

    Grogan J, Gupta R, Mahon KL, Stricker PD, Haynes AM, Delprado W, Turner J, Horvath LG, Kench JG (2017) Predictive value of the 2014 International Society of Urological Pathology grading system for prostate cancer in patients undergoing radical prostatectomy with long-term follow-up. BJU Int 120(5):651–658.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Wissing M, Brimo F, Chevalier S, Scarlata E, McKercher G, O’Flaherty A, Aprikian S, Thibodeau V, Saad F, Carmel M, Lacombe L, Tetu B, Ekindi-Ndongo N, Latour M, Trudel D, Aprikian A (2018) Optimization of the 2014 Gleason grade grouping in a Canadian cohort of patients with localized prostate cancer. BJU Int.

    Article  PubMed  Google Scholar 

  12. 12.

    Alenda O, Ploussard G, Mouracade P, Xylinas E, de la Taille A, Allory Y, Vordos D, Hoznek A, Abbou CC, Salomon L (2011) Impact of the primary Gleason pattern on biochemical recurrence-free survival after radical prostatectomy: a single-center cohort of 1,248 patients with Gleason 7 tumors. World J Urol 29(5):671–676.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Kirmiz S, Qi J, Babitz SK, Linsell S, Denton B, Singh K, Auffenberg G, Montie JE, Lane BR (2018) Grade groups provides improved predictions of pathologic and early oncologic outcomes compared with Gleason score risk groups. J Urol.

    Article  Google Scholar 

  14. 14.

    He J, Albertsen PC, Moore D, Rotter D, Demissie K, Lu-Yao G (2017) Validation of a contemporary five-tiered gleason grade grouping using population-based data. Eur Urol 71(5):760–763.

    Article  PubMed  Google Scholar 

  15. 15.

    Mathieu R, Moschini M, Beyer B, Gust KM, Seisen T, Briganti A, Karakiewicz P, Seitz C, Salomon L, de la Taille A, Roupret M, Graefen M, Shariat SF (2017) Prognostic value of the new grade groups in prostate cancer: a multi-institutional European validation study. Prostate Cancer Prostatic Dis 20(2):197–202.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Spratt DE, Jackson WC, Abugharib A, Tomlins SA, Dess RT, Soni PD, Lee JY, Zhao SG, Cole AI, Zumsteg ZS, Sandler H, Hamstra D, Hearn JW, Palapattu G, Mehra R, Morgan TM, Feng FY (2016) Independent validation of the prognostic capacity of the ISUP prostate cancer grade grouping system for radiation treated patients with long-term follow-up. Prostate Cancer Prostatic Dis 19(3):292–297.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi-Galluzzi C, Vickers AJ, Parwani AV, Reuter VE, Fine SW, Eastham JA, Wiklund P, Han M, Reddy CA, Ciezki JP, Nyberg T, Klein EA (2016) A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol 69(3):428–435.

    Article  PubMed  Google Scholar 

  18. 18.

    Berney DM, Beltran L, Fisher G, North BV, Greenberg D, Moller H, Soosay G, Scardino P, Cuzick J (2016) Validation of a contemporary prostate cancer grading system using prostate cancer death as outcome. Br J Cancer 114(10):1078–1083.

    Article  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Spratt DE, Cole AI, Palapattu GS, Weizer AZ, Jackson WC, Montgomery JS, Dess RT, Zhao SG, Lee JY, Wu A, Kunju LP, Talmich E, Miller DC, Hollenbeck BK, Tomlins SA, Feng FY, Mehra R, Morgan TM (2016) Independent surgical validation of the new prostate cancer grade-grouping system. BJU Int 118(5):763–769.

    Article  PubMed  Google Scholar 

  20. 20.

    Dell’Oglio P, Karnes RJ, Gandaglia G, Fossati N, Stabile A, Moschini M, Cucchiara V, Zaffuto E, Karakiewicz PI, Suardi N, Montorsi F, Briganti A (2017) The new prostate cancer grading system does not improve prediction of clinical recurrence after radical prostatectomy: results of a large, Two-Center Validation Study. Prostate 77(3):263–273.

    Article  PubMed  Google Scholar 

  21. 21.

    Yeong J, Sultana R, Teo J, Huang HH, Yuen J, Tan PH, Khor LY (2017) Gleason grade grouping of prostate cancer is of prognostic value in Asian men. J Clin Pathol 70(9):745–753.

    Article  PubMed  Google Scholar 

  22. 22.

    Schulman AA, Howard LE, Tay KJ, Tsivian E, Sze C, Amling CL, Aronson WJ, Cooperberg MR, Kane CJ, Terris MK, Freedland SJ, Polascik TJ (2017) Validation of the 2015 prostate cancer grade groups for predicting long-term oncologic outcomes in a shared equal-access health system. Cancer 123(21):4122–4129.

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Loeb S, Folkvaljon Y, Robinson D, Lissbrant IF, Egevad L, Stattin P (2016) Evaluation of the 2015 Gleason grade groups in a nationwide population-based cohort. Eur Urol 69(6):1135–1141.

    Article  PubMed  Google Scholar 

  24. 24.

    Pompe RS, Davis-Bondarenko H, Zaffuto E, Tian Z, Shariat SF, Leyh-Bannurah SR, Schiffmann J, Saad F, Huland H, Graefen M, Tilki D, Karakiewicz PI (2017) Population-based validation of the 2014 ISUP Gleason grade groups in patients treated with radical prostatectomy, brachytherapy, external beam radiation, or no local treatment. Prostate 77(6):686–693.

    Article  PubMed  Google Scholar 

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AO and MCH are supported by junior research grants from University of Luebeck.

Author information




AO: project development, data collection, data analysis, manuscript writing, data extraction. MCH: data collection, data analysis, manuscript writing, data extraction. VS: project development, manuscript editing. ASM: data analysis, manuscript editing. SP: project development, data analysis, manuscript editing, study supervision.

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Correspondence to S. Perner.

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Offermann, A., Hupe, M.C., Sailer, V. et al. The new ISUP 2014/WHO 2016 prostate cancer grade group system: first résumé 5 years after introduction and systemic review of the literature. World J Urol 38, 657–662 (2020).

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  • Grade group
  • International Society of Urological Pathology (ISUP)
  • Prognosis
  • Prostate cancer
  • World Health Organization (WHO)