Original Study| Volume 15, ISSUE 6, e907-e913, December 2017

Grade Group Underestimation in Prostate Biopsy: Predictive Factors and Outcomes in Candidates for Active Surveillance

Published:April 25, 2017DOI:



      We intended to analyze the outcomes and predictive factors for underestimating the prostate cancer (PCa) grade group (GG) from prostate biopsies in a large monocentric cohort of patients treated by minimally invasive radical prostatectomy (RP).

      Materials and Methods

      Using a monocentric prospectively maintained database, we included 3062 patients who underwent minimally invasive RP between 2006 and 2013. We explored clinicopathologic features and outcomes associated with a GG upgrade from biopsy to RP. Multivariate logistic regression was used to develop and validate a nomogram to predict upgrading for GG1.


      Biopsy GG was upgraded after RP in 51.5% of cases. Patients upgraded from GG1 to GG2 or GG3 after RP had a longer time to biochemical recurrence than those with GG2 or GG3 respectively, on both biopsy and RP, but a shorter time to biochemical recurrence than those who remained GG1 after RP (P < .0001). In multivariate analyses, variables predicting upgrading for GG1 PCa were age (P = .0014), abnormal digital rectal examination (P < .0001), prostate-specific antigen density (P < .0001), percentage of positive cores (P < .0001), and body mass index (P = .037). A nomogram was generated and validated internally.


      Biopsy grading system is misleading in approximately 50% of cases. Upgrading GG from biopsy to RP may have consequences on clinical outcomes. A nomogram using clinicopathologic features could aid the probability of needing to upgrade GG1 patients at their initial evaluation.


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        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer statistics, 2016.
        CA Cancer J Clin. 2016; 66: 7-30
        • Miller D.C.
        • Gruber S.B.
        • Hollenbeck B.K.
        • Montie J.E.
        • Wei J.T.
        Incidence of initial local therapy among men with lower-risk prostate cancer in the United States.
        J Natl Cancer Inst. 2006; 98: 1134-1141
        • Chun F.K.
        • Steuber T.
        • Erbersdobler A.
        • et al.
        Development and internal validation of a nomogram predicting the probability of prostate cancer Gleason sum upgrading between biopsy and radical prostatectomy pathology.
        Eur Urol. 2006; 49: 820-826
        • Epstein J.I.
        • Feng Z.
        • Trock B.J.
        • Pierorazio P.M.
        Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades.
        Eur Urol. 2012; 61: 1019-1024
        • Eggener S.E.
        • Scardino P.T.
        • Walsh P.C.
        • et al.
        Predicting 15-year prostate cancer specific mortality after radical prostatectomy.
        J Urol. 2011; 185: 869-875
        • Epstein J.I.
        • Egevad L.
        • Amin M.B.
        • et al.
        The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: definition of grading patterns and proposal for a new grading system.
        Am J Surg Pathol. 2016; 40: 244-252
        • Epstein J.I.
        • Allsbrook W.C.
        • Amin M.B.
        • Egevad L.L.
        • ISUP Grading Committee
        The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma.
        Am J Surg Pathol. 2005; 29: 1228-1242
        • Klotz L.
        • Vesprini D.
        • Sethukavalan P.
        • et al.
        Long-term follow-up of a large active surveillance cohort of patients with prostate cancer.
        J Clin Oncol. 2015; 33: 272-277
        • Tosoian J.J.
        • Trock B.J.
        • Landis P.
        • et al.
        Active surveillance program for prostate cancer: an update of the Johns Hopkins experience.
        J Clin Oncol. 2011; 29: 2185-2190
        • van den Bergh R.C.N.
        • Roemeling S.
        • Roobol M.J.
        • et al.
        Outcomes of men with screen-detected prostate cancer eligible for active surveillance who were managed expectantly.
        Eur Urol. 2009; 55: 1-8
        • van As N.J.
        • Norman A.R.
        • Thomas K.
        • et al.
        Predicting the probability of deferred radical treatment for localised prostate cancer managed by active surveillance.
        Eur Urol. 2008; 54: 1297-1305
        • Dall'era M.A.
        • Konety B.R.
        • Cowan J.E.
        • et al.
        Active surveillance for the management of prostate cancer in a contemporary cohort.
        Cancer. 2008; 112: 2664-2670
        • Berglund R.K.
        • Masterson T.A.
        • Vora K.C.
        • Eggener S.E.
        • Eastham J.A.
        • Guillonneau B.D.
        Pathological upgrading and up staging with immediate repeat biopsy in patients eligible for active surveillance.
        J Urol. 2008; 180 (discussion: 1967-8): 1964-1967
        • Lu-Yao G.L.
        • Albertsen P.C.
        • Moore D.F.
        • et al.
        Outcomes of localized prostate cancer following conservative management.
        JAMA. 2009; 302: 1202-1209
        • Melia J.
        • Moseley R.
        • Ball R.Y.
        • et al.
        A UK-based investigation of inter- and intra-observer reproducibility of Gleason grading of prostatic biopsies.
        Histopathology. 2006; 48: 644-654
        • Fine S.W.
        • Epstein J.I.
        A contemporary study correlating prostate needle biopsy and radical prostatectomy Gleason score.
        J Urol. 2008; 179 (discussion: 1338-9): 1335-1338
        • Bastian P.J.
        • Carter B.H.
        • Bjartell A.
        • et al.
        Insignificant prostate cancer and active surveillance: from definition to clinical implications.
        Eur Urol. 2009; 55: 1321-1330
        • Corcoran N.M.
        • Hong M.K.H.
        • Casey R.G.
        • et al.
        Upgrade in Gleason score between prostate biopsies and pathology following radical prostatectomy significantly impacts upon the risk of biochemical recurrence.
        BJU Int. 2011; 108: E202-E210
        • Otaibi Al M.
        • Ross P.
        • Fahmy N.
        • et al.
        Role of repeated biopsy of the prostate in predicting disease progression in patients with prostate cancer on active surveillance.
        Cancer. 2008; 113: 286-292
        • Müntener M.
        • Epstein J.I.
        • Hernandez D.J.
        • et al.
        Prognostic significance of Gleason score discrepancies between needle biopsy and radical prostatectomy.
        Eur Urol. 2008; 53 (discussion: 775-6): 767-775
        • Jo J.K.
        • Hong S.K.
        • Byun S.-S.
        • Lee S.E.
        • Lee S.
        • Oh J.J.
        Prognostic significance of the disparity between biopsy and pathologic gleason score after radical prostatectomy in clinical candidates for active surveillance according to the Royal Marsden Criteria.
        Clin Genitourin Cancer. 2016; 14: e329-e333
        • D'Amico A.V.
        • Renshaw A.A.
        • Arsenault L.
        • Schultz D.
        • Richie J.P.
        Clinical predictors of upgrading to Gleason grade 4 or 5 disease at radical prostatectomy: potential implications for patient selection for radiation and androgen suppression therapy.
        Int J Radiat Oncol Biol Phys. 2013; 45: 841-846
        • Iremashvili V.
        • Manoharan M.
        • Pelaez L.
        • Rosenberg D.L.
        • Soloway M.S.
        Clinically significant Gleason sum upgrade: external validation and head-to-head comparison of the existing nomograms.
        Cancer. 2012; 118: 378-385
        • Kulkarni G.S.
        • Lockwood G.
        • Evans A.
        • et al.
        Clinical predictors of Gleason score upgrading: implications for patients considering watchful waiting, active surveillance, or brachytherapy.
        Cancer. 2007; 109: 2432-2438
        • Capitanio U.
        • Karakiewicz P.I.
        • Valiquette L.
        • et al.
        Biopsy core number represents one of foremost predictors of clinically significant gleason sum upgrading in patients with low-risk prostate cancer.
        Urology. 2009; 73: 1087-1091
        • Moussa A.S.
        • Kattan M.W.
        • Berglund R.
        • Yu C.
        • Fareed K.
        • Jones J.S.
        A nomogram for predicting upgrading in patients with low- and intermediate-grade prostate cancer in the era of extended prostate sampling.
        BJU Int. 2010; 105: 352-358
        • Truong M.
        • Slezak J.A.
        • Lin C.P.
        • et al.
        Development and multi-institutional validation of an upgrading risk tool for Gleason 6 prostate cancer.
        Cancer. 2013; 119: 3992-4002
        • Seisen T.
        • Roudot-Thoraval F.
        • Bosset P.O.
        • et al.
        Predicting the risk of harboring high-grade disease for patients diagnosed with prostate cancer scored as Gleason ≤ 6 on biopsy cores.
        World J Urol. 2015; 33: 787-792
        • Leyh-Bannurah S.-R.
        • Abou-Haidar H.
        • Dell'Oglio P.
        • et al.
        Primary Gleason pattern upgrading in contemporary D'Amico low-risk prostate cancer patients: implications for future biomarkers and imaging modalities.
        BJU Int. 2017; 119: 692-699
        • Onik G.
        • Miessau M.
        • Bostwick D.G.
        Three-dimensional prostate mapping biopsy has a potentially significant impact on prostate cancer management.
        J Clin Oncol. 2009; 27: 4321-4326
        • Le J.D.
        • Tan N.
        • Shkolyar E.
        • et al.
        Multifocality and prostate cancer detection by multiparametric magnetic resonance imaging: correlation with whole-mount histopathology.
        Eur Urol. 2015; 67: 569-576
        • Radtke J.P.
        • Schwab C.
        • Wolf M.B.
        • et al.
        Multiparametric magnetic resonance imaging (MRI) and MRI-transrectal ultrasound fusion biopsy for index tumor detection: correlation with radical prostatectomy specimen.
        Eur Urol. 2016; 70: 846-853
        • Ahmed H.U.
        • El-Shater Bosaily A.
        • Brown L.C.
        • et al.
        Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study.
        Lancet. 2017; 389: 815-822