Gleason Grade Articles


  • A Contemporary Prostate Cancer Grading System: A Validated Alternative to the Gleason Score.

    Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, 8-10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3+4=7 and 4+3=7 are often considered the same prognostic group.

    Published August 3, 2015
  • Active Surveillance: Pathologic and Clinical Variables Associated with Outcome.

    Over the past 10 years, active surveillance has emerged as a primary management option for men diagnosed with low-risk prostate cancer. Given the morbidity associated with curative treatment, active surveillance maintains quality of life for men whose disease may never become symptomatic.

    Published December 17, 2015
  • Beyond the Abstract - Elevated expression of cancer-associated proliferating cell nuclear antigen in high-grade prostatic intraepithelial neoplasia and prostate cancer, by George E. Sandusky, DVM, PhD

    BERKELEY, CA ( - Prostate cancer is one of the leading forms of cancer in industrial countries.

    Published June 6, 2011
  • Changes in prostate cancer grading: Including a new patient-centric grading system.

    The first structured approach to grade prostate cancer based on the underlying histological architecture was developed by Donald Gleason who in 1966 proposed a morphologic classification of prostate cancer and in 1974 demonstrated its clinical significance based on prostate cancer-specific death.

    Published January 1, 2016
  • Correlation of mRNA-PCA3 urine levels with the new grading system in prostate cancer.

    To evaluate the PCA3 (Prostate Cancer 3 gene) as a tool to improve prostate cancer (PCa) screening and its capability to predict PCa aggressiveness.

    A retrospective study with data from consecutive patients with suspected PCa seen in the urology department between November 2009 and April 2016 and who were candidates for prostate biopsy.

    Published December 27, 2018
  • Development of a Deep Learning Algorithm for the Histopathologic Diagnosis and Gleason Grading of Prostate Cancer Biopsies: A Pilot Study.

    The pathologic diagnosis and Gleason grading of prostate cancer are time-consuming, error-prone, and subject to interobserver variability. Machine learning offers opportunities to improve the diagnosis, risk stratification, and prognostication of prostate cancer.

    Published December 2, 2019
  • Epigenetic risk score improves prostate cancer risk assessment.

    Early detection of aggressive prostate cancer (PCa) remains crucial for effective treatment of patients. However, PCa screening remains controversial due to a high rate of overdiagnosis and overtreatment.

    Published August 9, 2017
  • Evaluation and active treatment versus active surveillance of localized prostate cancer in renal transplant patients in the era of low and very low risk prostate cancer.

    Current trends in renal transplantation such as improvement of allograft/ recipient survivals and expansion of organ transplantation eligibility criteria into older recipients are concomitant with increasingly detected low risk prostate cancer (PCa) in candidates for or recipients of renal transplantation.

    Published March 7, 2019
  • Evaluation of the 2015 Gleason Grade Groups in a Nationwide Population-based Cohort.

    New five-tiered Gleason grade groups (GGGs) were recently proposed, in which Gleason 6 is GGG 1, Gleason 3+4 is GGG 2, Gleason 4+3 is GGG 3, Gleason 8 is GGG 4, and Gleason 9-10 is GGG 5.

    To examine the performance of the new GGGs in men with prostate cancer from a nationwide population-based cohort.

    Published January 1, 2016
  • Extreme Gleason Upgrading From Biopsy to Radical Prostatectomy: A Population-Based Analysis.

    To examine the risk factors associated with the odds of extreme Gleason upgrading at RP (defined as a Gleason prognostic group score increase of ≥ 2), we utilized a large, population-based cancer registry.

    Published July 1, 2016
  • Identifying the Best Candidates for Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography as the Primary Staging Approach Among Men with High-risk Prostate Cancer and Negative Conventional Imaging.

    Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is an emerging imaging modality with greater sensitivity and specificity over conventional imaging for prostate cancer (PCa) staging.

    Published February 22, 2021
  • International Society of Urological Pathology (ISUP) grading of prostate cancer - An ISUP consensus on contemporary grading.

    The International Society of Urological Pathology (ISUP) has issued guidelines for the grading of prostate cancer based on a consensus conference held in 2014. The recommendations resulting from the 2014 consensus conference were a further development of 2005 ISUP modified Gleason grading.

    Published May 9, 2016
  • Is transperineal prostate biopsy more accurate than transrectal biopsy in determining final Gleason score and clinical risk category? A comparative analysis.

    To assess the degree of upgrading and increase in clinical risk category of transperineal template biopsy (TTB) compared with transrectal ultrasonography-guided prostate biopsy (TRUSB). Upgrading of TRUSB Gleason grade and sum after radical prostatectomy (RP) is well recognised.

    Published September 21, 2015
  • Loss of AZGP1 as a Superior Predictor of Relapse in Margin-Positive Localized Prostate Cancer.

    Positive surgical margins (PSMs) in localized prostate cancer (PC) confer a two- to three-fold increased risk of biochemical relapse (BR). Absent/weak AZGP1 expression and Gleason grade ≥4 at the margin are each independent predictors of BR in patients with PSMs.

    Published August 1, 2016
  • Management of prostate cancer patients with locally adverse pathologic features after radical prostatectomy: feasibility of active surveillance for cases with Gleason grade 3 + 4 = 7.

    To evaluate the ability of the new Gleason grade groups (GGGs) to stratify risk in prostate cancer patients with locally adverse pathologic features after radical prostatectomy (RP) thereby allowing more accurate assessment for planning eventual adjuvant therapy.

    Published September 30, 2016
  • Pathological upgrading in prostate cancer treated with surgery in the United Kingdom: trends and risk factors from the British Association of Urological Surgeons Radical Prostatectomy Registry.

    Accurate grading at the time of diagnosis if fundamental to risk stratification and treatment decision making in patients with prostate cancer. Whilst previous studies have demonstrated significant pathological upgrading and downgrading following radical prostatectomy (RP), these were based on historical cohorts and do not reflect contemporary patient selection and management practices.

    Published November 29, 2019
  • Performance characteristics of prostate-specific antigen density and biopsy primary Gleason score to predict biochemical failure in patients with intermediate prostate cancer who underwent radical prostatectomy.

    Prognosis for intermediate-risk prostate cancer (PCa) remains variable; therefore, we aimed to investigate high-risk factors for biochemical recurrence (BCR), and intermediate-risk PCa using radical prostatectomy to identify patients having equivalent BCR-free survival rates when compared to high-risk PCa.

    Published February 26, 2019
  • Prognostic Value of Gleason Score at Positive Surgical Margin in Prostate Cancer: A Systematic Review and Meta-analysis.

    The individual clinical significance of a positive surgical margin (PSM) after radical prostatectomy has remained controversial. Studies have suggested that the Gleason grade (GG) at the PSM could improve predictive accuracy and decision making.

    Published April 9, 2020
  • Prostate Cancer Grading & Staging Systems

     The clinical staging of prostate cancer uses pretreatment parameters to predict the extent of disease, for assessment of prognosis and to assist in decisions regarding appropriate treatment.  Pretreatment information used to predict disease extent in men with prostate cancer include DRE (T stage), PSA and its derivatives, prostate cancer features on needle biopsy, and in recurrent disease radiologic imaging.  

    • Pathologic stage is determined after prostate removal and involves histologic analysis of the prostate, seminal vesicles, and pelvic lymph nodes if lymphadenectomy is performed.
    • Pathologic staging more accurately estimates disease burden and is more useful than clinical staging for outcome prediction.  The most important pathologic criteria that predict prognosis after radical prostatectomy are tumor grade, surgical margin status, extracapsular disease, seminal vesicle invasion, and pelvic lymph node involvement.
    • Biochemical recurrence-free survival and cancer-specific survival are both inversely related to the pathologic stage of disease.


    • This is a system based on the degree of glandular differentiation and growth pattern. Five patterns have been described.
    • A Gleason "score" is given for each tumor, representing the sum of the two most common patterns displayed. The scores range from 2 to 10 and have some prognostic predictive value at the very low or very high ranges.
    • This is the most commonly used grading system for prostate adenocarcinoma


    Anatomic Stage / Prognostic Groups
     Group  T  N M PSA  Gleason

     T1a-c  NO  MO  PSA < 10  Gleason ≤ 6
     T2a  NO  MO  PSA < 10  Gleason ≤ 6
     T1-2a  NO  MO  PSA X  Gleason X

     T1a-c  NO  MO  PSA<20  Gleason 7
     T1a-c  NO  MO  PSA≥10<20  Gleason ≤ 6
     T2a  NO  MO  PSA≥10<20  Gleason ≤6
     T2a  NO  MO  PSA<20  Gleason 7
     T2b  NO  MO  PSA<20  Gleason ≤7
     T2b  NO  MO  PSA X  Gleason X

     T2c  NO  MO  Any PSA  Any Gleason
     T1-2  NO  MO  PSA ≥ 20  Any Gleason
     T1-2  NO  MO  Any PSA  Gleason ≥8
    III  T3a-b  NO  MO  Any PSA  Any Gleason

     T4  NO  MO  Any PSA  Any Gleason
     Any T  N1  MO  Any PSA  Any Gleason
     Any T  Any N  M1  Any PSA  Any Gleason
    Prostate Cancer Primary Tumor [T] TNM Clinical Staging System AJCC 2010
    TX Primary tumor cannot be assessed
    T0 No evidence of primary tumor
    T1 Clinically inapparent tumor neither palpable nor visible by imaging
    T1a Normal DRE; incidental tumor ≤ 5% of total surgical specimen in histological finding
    T1b Normal DRE: incidental tumor > 5% of specimen, any grade, or < 5% of resected specimen 
    T1c Normal DRE; tumor identified by prostate needle biopsy (e.g. elevated PSA)
    T2 Tumor confined to the prostate [1]
    T2a Organ-confined limited to one half of one lobe of the prostate or less
    T2b Organ-confined; more than one half of a lobe but not both lobes
    T2c Tumor involves both lobes
    T3 Tumor extends through the prostate capsule [2]
    T3a Extracapsular extension (unilateral or bilateral)
    T3b Tumor invades seminal vesicle(s)
    T4 Tumor is fixed or invades adjacent structures other than seminal vesicles (e.g., bladder, rectum)

    [1]  Tumor found in one or both lobes by needle biopsy, but not palpable or reliably visiblle by imaging, is classified as T1c.
    [2]  Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is classified not as T3, but as T2.

    Regional Lymph Nodes (N) Clinical 
    NX Regional lymph nodes were not assessed
    N0 No regional lymph node metastasis
    N1 Metastasis in regional lymph node(s)
      Regional Lymph Node (N) Pathologic
     pNX  Regional nodes not sampled
     pN0  No positive regional nodes
     pN1  Metastases in regional node(s)


    Distant Metastasis (M) [5]
    M0 No distant metastasis
    M1 Distant metastasis 
    M1a Nonregional lymph node(s) metastasis 
    M1b Bone(s) metastasis 
    M1c Other metastatic site(s) with or without bone disease


    [5] When more than one site of metastasis is present, the most advanced category is used. pM1c is most advanced.

    G1 Well differentiated (Gleason score 2 -4)
    G2 Moderately differentiated (Gleason score 5-6)
    G3-4 Poorly differentiated or undifferentiated (marked anaplasia) (Gleason score 7-10)


    Clinical Stage Grouping
    G1 G2-4 Any Grade
    T1a T1bc T2 T3 T4
    Pathologic Stage [3]
    pT2 Tumor confined to the prostate
    T2a Unilateral, involving one half of one lobe or less
    T2b Unilateral, more than one half of a lobe but not both
    T2c Tumor involves both lobes
    T3 Extraprostatic extension [4]
    T3a Extracapsular extension (unilateral or bilateral)
    T3b Seminal vesicle invasion
    T4 Invasion of bladder or rectum


    [3] There is no pathologic T1 description
    [4] Positive margin of resection denoted by an R1 descriptor (residual microscopic disease).



    The recent regulatory approval of the semiautomated CellSearch system (Veridex, Raritan, NJ) for monitoring prostate cancer, has led to investigation to determine whether circulating tumor cells have a role in the staging of early disease.  



    • American Joint Committee on Cancer (2010). Prostate. In AJCC Cancer Staging Manual, 7th ed.  (Part IX. Genitourinary Sites - Prostate) Edge, S.B.; Byrd, D.R.; Compton, C.C.; Fritz, A.G.; Greene, F.L.; Trotti, A. (Eds.)

    • Davis et al, 2008. Davis JW, Nakanishi H, Kumar VS, et al: Circulating tumor cells in peripheral blood samples from patients with increased serum prostate specific antigen: initial results in early prostate cancer. J Urol  2008; 179(6):2187-2191.

    • Helo et al, 2009. Helo P, Cronin AM, Danila DC, et al: Circulating prostate tumor cells detected by reverse transcription-pcr in men with localized or castration-refractory prostate cancer: concordance with CellSearch assay and association with bone metastases and with survival. Clin Chem  2009; 55(4):765-773.

    • Lin EH, Lozano R and Karp DD. Color-Matrix Cancer Staging and Treatment Handbook, 3rd edition. The University of Texas MD Anderson Cancer Center, 2004, p. 28.

    • Pound et al, 1997. Pound CR, Partin AW, Epstein JI, et al: Prostate-specific antigen after anatomic radical retropubic prostatectomy. Patterns of recurrence and cancer control. Urol Clin North Am  1997; 24(2):395-406.

    Published April 1, 2012
  • Prostatic Adenocarcinoma: A Grading from Gleason to the New Grade-Group System: A Historical and Critical Review

    The introduction of the Gleason grading system revolutionised prognostic parameters and determination of patient treatment regiments for prostatic adenocarcinomas, and has become synonymous with prostate cancer, almost universally applied in clinical settings to predict radical prostatectomy specimen findings, potential biochemical failure, local recurrences, lymph nodes or distant metastases in patients not receiving any treatment as well as those receiving treatment including radiation therapy, surgical treatment such as radical prostatectomy and other therapies etc,.

    Published May 1, 2019
  • Reporting Gleason grade/score in synoptic reports of radical prostatectomies.

    The format of a synoptic report can significantly affect the accuracy, speed, and preference with which a reader can retrieve information.

    The objective of this study is to compare different formats of Gleason grading/score in synoptic reports of radical prostatectomies.

    Published February 17, 2017
  • Significance of Paneth-cell-like differentiation in prostatic adenocarcinoma: A retrospective cohort study of 80 cases.

    The grading and prognosis of prostatic adenocarcinoma with Paneth cell-like differentiation (PanEC) of the prostate is controversial with limited available data. We identified 80 cases, not previously published, of PanEC first identified on biopsy (n=69), transurethral resection (TURP)(n=1) and radical prostatectomy (RP) (n=10).

    Published May 29, 2020
  • The Accuracy of Prostate Biopsies for Predicting Gleason Score in Radical Prostatectomy Specimens. Nationwide trends 2000-2012.

    OBJECTIVES - To investigate how well the Gleason score in diagnostic needle biopsies predicted the Gleason score in a subsequent radical prostatectomy (RP) specimen before and after the 2005 International Society of Urological Pathology (ISUP) revision of Gleason grading, and if the recently proposed ISUP grades 1-5 (corresponding to Gleason score 6, 3+4, 4+3, 8, and 9-10) better predict the RP grade.

    Published March 2, 2016
  • The impact of downgrading from biopsy Gleason 7 to prostatectomy Gleason 6 on biochemical recurrence and prostate cancer-specific mortality.

    Gleason score (GS) is one of the most important prognostic indicators for prostate cancer (PC). Downgrading from biopsy (Bx) GS 7 to radical prostatectomy (RP) GS 6 occurs commonly, yet the impact on survival outcomes is unknown.

    Published November 23, 2016
  • The New Prostate Cancer Grading System Does Not Improve Prediction of Clinical Recurrence After Radical Prostatectomy: Results of a Large, Two-Center Validation Study.

    A new prostate cancer (PCa) grading system (namely, Gleason score-GS- ≤6 vs. 3 + 4 vs. 4 + 3 vs. 8 vs. ≥9) was recently proposed and assessed on biochemical recurrence (BCR) showing improved predictive abilities compared to the commonly used three-tier system (GS ≤6 vs.

    Published October 28, 2016
  • The prognostic impact of downgrading and upgrading from biopsy to radical prostatectomy among men with Gleason score 7 prostate cancer.

    Recently, a new prostate cancer (PC) grading system was introduced, where Gleason score (GS) 7 was divided into 3 + 4 = 7 and 4 + 3 = 7 due to the different prognoses associated with each tumor type.

    Published September 6, 2019
  • Trop-2 is up-regulated in invasive prostate cancer and displaces FAK from focal contacts.

    In this study, we show that the transmembrane glycoprotein Trop-2 is up-regulated in human prostate cancer (PCa) with extracapsular extension (stages pT3/pT4) as compared to organ-confined (stage pT2) PCa.

    Published July 26, 2015
  • Validation of the 2015 prostate cancer grade groups for predicting long-term oncologic outcomes in a shared equal-access health system.

    A 5-tier prognostic grade group (GG) system was enacted to simplify the risk stratification of patients with prostate cancer in which Gleason scores of ≤6, 3 + 4, 4 + 3, 8, and 9 or 10 are considered GG 1 through 5, respectively.

    Published July 7, 2017
  • Validation of the novel ISUP-2014 5-tier Gleason grade grouping: Biochemical recurrence rates of 3+5 disease may be overestimated.

    In 2014 the International Society of Urological Pathology (ISUP) supported to change the ISUP-2005 modified Gleason scoring system, as previously proposed by Pierorazio et al.[1,2] Besides decisions on terminology and scoring of specific morphological patterns, a renumbering of the existing scores was suggested.

    Published March 23, 2016
  • Vascular morphology differentiates prostate cancer mortality risk among men with higher Gleason grade.

    Higher Gleason grade is associated with prostate cancer mortality; however, there is significant heterogeneity in this association. We evaluated whether vessel morphology, a biomarker of angiogenesis, aided in distinguishing mortality risks among men with high Gleason grading.

    Published July 8, 2016