Contemporary Grading for Prostate Cancer: Implications for Patient Care ☆

CONTEXT The Gleason grading system is one of the most powerful predictors of outcome in prostate cancer and a cornerstone in counseling and treating patients. Since its inception, it has undergone several modifications triggered by a change in clinical practice and a better understanding of the cancer's histologic spectrum and variants and their prognostic significance. OBJECTIVE To provide an overview of the implementation and the impact of the Gleason system as a predictive and prognostic tool in all available treatment modalities, and to compare the original and modified Gleason systems in major pathologic and clinical outcome data sets. EVIDENCE ACQUISITION A comprehensive nonsystematic Medline search was performed using multiple Medical Subject Headings such as Gleason, modified, system, outcome, biopsy, prostatectomy, recurrence, prognosis, radiotherapy, and focal therapy, with restriction to the English language and a preference for publications within the last 10 yr. All Gleason grade-related studies in the last 3 yr were reviewed. For studies before this date, we relied on prior culling of the literature for various recent books, chapters, and original articles on this topic. EVIDENCE SYNTHESIS Using the modified grading system resulted in disease upgrading with more cancers assigned a Gleason score ≥ 7 than in the past. It also resulted in a more homogeneous Gleason score 6, which has an excellent prognosis when the disease is organ confined. The vast majority of studies using both systems showed that Gleason grading of adenocarcinomas on needle biopsies and radical prostatectomies was strongly associated with pathologic stage, status of surgical margins, metastatic disease, biochemical recurrence, and cancer-specific survival, with the modified system outperforming the original one in some large series. A description of the continuous incorporation of this parameter in the clinical decision making for treating prostate cancer using all currently used treatment modalities is presented, and the findings of studies before and after the inception of the modified grading system, if available, are compared. The proposed contemporary grading prognostic categories are 3+3, 3+4, 4+3, 8, and 9-10. CONCLUSIONS The Gleason score is one of the most critical predictive factors of prostate cancer regardless of the therapy used. Modernization of the Gleason grading system has resulted in a more accurate grading system for radical prostatectomy (RP) but has complicated the comparison of data before and after the updating. A better prognostication with the updated Gleason grading system for patients treated with modalities other than surgery can only be postulated at this time because there are limited conflicting data on radiation and no studies on other treatment modalities. Its greatest impact is the uniformly excellent prognosis associated with Gleason score 6 in RPs.

[1]  H. Sandler,et al.  Continued benefit to androgen deprivation therapy for prostate cancer patients treated with dose-escalated radiation therapy across multiple definitions of high-risk disease. , 2011, International journal of radiation oncology, biology, physics.

[2]  M. Cooperberg,et al.  Active surveillance for the management of prostate cancer in a contemporary cohort , 2008, Cancer.

[3]  Kevin C Zorn,et al.  The Will Rogers phenomenon in urological oncology. , 2008, The Journal of urology.

[4]  J. Blasko,et al.  Interstitial implant alone or in combination with external beam radiation therapy for intermediate-risk prostate cancer: a survey of practice patterns in the United States. , 2007, Brachytherapy.

[5]  L. Egevad,et al.  Implications of the International Society of Urological Pathology modified Gleason grading system. , 2012, Archives of pathology & laboratory medicine.

[6]  A. Partin,et al.  Tumor grade at margins of resection in radical prostatectomy specimens is an independent predictor of prognosis. , 2010, Urology.

[7]  K. Wallner,et al.  Distant metastases following permanent interstitial brachytherapy for patients with clinically localized prostate cancer. , 2011, International journal of radiation oncology, biology, physics.

[8]  T. Stamey,et al.  Biological determinants of cancer progression in men with prostate cancer. , 1999, JAMA.

[9]  A. Partin,et al.  Preoperative characteristics of high‐Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy , 2012, BJU international.

[10]  Oliver Sartor,et al.  Focal therapy for localized prostate cancer: a critical appraisal of rationale and modalities. , 2007, The Journal of urology.

[11]  H. G. van der Poel,et al.  Salvage radical prostatectomy for radiation-recurrent prostate cancer: a multi-institutional collaboration. , 2011, European urology.

[12]  Alan W Partin,et al.  Updated nomogram to predict pathologic stage of prostate cancer given prostate-specific antigen level, clinical stage, and biopsy Gleason score (Partin tables) based on cases from 2000 to 2005. , 2007, Urology.

[13]  E. Barret,et al.  Focal therapy with high-intensity focused ultrasound for prostate cancer in the elderly. A feasibility study with 10 years follow-up. , 2011, International braz j urol : official journal of the Brazilian Society of Urology.

[14]  B. Trock,et al.  Natural history of pathologically organ-confined (pT2), Gleason score 6 or less, prostate cancer after radical prostatectomy. , 2008, Urology.

[15]  A. Evans,et al.  Prostatic needle biopsies following primary high intensity focused ultrasound (HIFU) therapy for prostatic adenocarcinoma: histopathological features in tumour and non-tumour tissue , 2012, Journal of Clinical Pathology.

[16]  S B Malkowicz,et al.  Biochemical Outcome After Radical Prostatectomy , External Beam Radiation Therapy , or Interstitial Radiation Therapy for Clinically Localized Prostate Cancer , 2000 .

[17]  D. Gleason Classification of prostatic carcinomas. , 1966, Cancer chemotherapy reports.

[18]  A W Partin,et al.  Prognostic significance of Gleason score 3+4 versus Gleason score 4+3 tumor at radical prostatectomy. , 2000, Urology.

[19]  J. Epstein,et al.  Should each core with prostate cancer be assigned a separate gleason score? , 2003, Human pathology.

[20]  J. Epstein,et al.  Change in prostate cancer grade over time in men followed expectantly for stage T1c disease. , 2008, The Journal of urology.

[21]  Steven Piantadosi,et al.  Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. , 2003, The Journal of urology.

[22]  J. Ciezki,et al.  Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. , 2012, International journal of radiation oncology, biology, physics.

[23]  M Emberton,et al.  Focal therapy in prostate cancer-report from a consensus panel. , 2010, Journal of endourology.

[24]  Jeffrey K. Cohen,et al.  A pretreatment nomogram predicting biochemical failure after salvage cryotherapy for locally recurrent prostate cancer , 2009, BJU international.

[25]  M. Cooperberg,et al.  The University of California, San Francisco Cancer of the Prostate Risk Assessment score: a straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy. , 2005, The Journal of urology.

[26]  P. Humphrey,et al.  The Gleason Score of Tumor at the Margin in Radical Prostatectomy is Predictive of Biochemical Recurrence , 2010, The American journal of surgical pathology.

[27]  L. Egevad,et al.  Correlation of modified Gleason grading of prostate carcinoma with age, serum prostate specific antigen and tumor extent in needle biopsy specimens. , 2008, Analytical and quantitative cytology and histology.

[28]  Alan W Partin,et al.  Active Surveillance Program for Prostate Cancer: An Update of the Johns Hopkins Experience , 2011 .

[29]  Lars Egevad,et al.  A contemporary update on pathology reporting for prostate cancer: biopsy and radical prostatectomy specimens. , 2012, European urology.

[30]  A. Billis Percent Gleason grade (4/5) as prognostic factor in prostate cancer diagnosed at transurethral resection. , 2002, International braz j urol : official journal of the Brazilian Society of Urology.

[31]  T. H. van der Kwast,et al.  Should we replace the Gleason score with the amount of high-grade prostate cancer? , 2007, European urology.

[32]  B. Trock,et al.  The natural history of metastatic progression in men with prostate‐specific antigen recurrence after radical prostatectomy: long‐term follow‐up , 2012, BJU International.

[33]  X. Rébillard,et al.  High‐intensity focused ultrasound in prostate cancer; a systematic literature review of the French Association of Urology , 2008, BJU international.

[34]  D. Chan,et al.  The use of prostate specific antigen, clinical stage and Gleason score to predict pathological stage in men with localized prostate cancer. , 1993, The Journal of urology.

[35]  C. Pan,et al.  The prognostic significance of tertiary Gleason patterns of higher grade in radical prostatectomy specimens: a proposal to modify the Gleason grading system. , 2000, The American journal of surgical pathology.

[36]  Y. Inayama,et al.  Usefulness of the 2005 International Society of Urologic Pathology Gleason grading system in prostate biopsy and radical prostatectomy specimens , 2009, BJU international.

[37]  J. Epstein,et al.  A contemporary study correlating prostate needle biopsy and radical prostatectomy Gleason score. , 2008, The Journal of urology.

[38]  Y. Yamada,et al.  Ten‐year outcomes of high‐dose, intensity‐modulated radiotherapy for localized prostate cancer , 2011, Cancer.

[39]  R. Stock,et al.  Disease-specific survival following the brachytherapy management of prostate cancer. , 2006, International journal of radiation oncology, biology, physics.

[40]  N. Lawrentschuk,et al.  Active surveillance for low-risk prostate cancer: an update , 2011, Nature Reviews Urology.

[41]  P. Walsh,et al.  Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. , 1994, JAMA.

[42]  Bruce J Trock,et al.  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. , 2012, European urology.

[43]  P. Unger,et al.  Influence of pretreatment and treatment factors on intermediate to long-term outcome after prostate brachytherapy. , 2011, The Journal of urology.

[44]  John T. Wei,et al.  Multiple prostate cancer cores with different Gleason grades submitted in the same specimen container without specific site designation: should each core be assigned an individual Gleason score? , 2009, Human pathology.

[45]  H. Sandler,et al.  Gleason pattern 5 is the greatest risk factor for clinical failure and death from prostate cancer after dose-escalated radiation therapy and hormonal ablation. , 2011, International journal of radiation oncology, biology, physics.

[46]  L. Egevad,et al.  The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma , 2005, The American journal of surgical pathology.

[47]  D. Bostwick,et al.  Prognostic factors for survival of patients with pathological Gleason score 7 prostate cancer: differences in outcome between primary Gleason grades 3 and 4. , 2001, The Journal of urology.

[48]  J. Cuzick,et al.  Major shifts in the treatment and prognosis of prostate cancer due to changes in pathological diagnosis and grading , 2007, BJU international.

[49]  Jennifer L. Beebe-Dimmer,et al.  Prognostic Gleason grade grouping : data based on the modified Gleason scoring system , 2013 .

[50]  S. Crouzet,et al.  Multicentric oncologic outcomes of high-intensity focused ultrasound for localized prostate cancer in 803 patients. , 2010, European urology.

[51]  A. Dal Pra,et al.  Combining radiation therapy and androgen deprivation for localized prostate cancer-a critical review. , 2010, Current oncology.

[52]  Chin-Lee Wu,et al.  Impact on the Clinical Outcome of Prostate Cancer by the 2005 International Society of Urological Pathology Modified Gleason Grading System , 2012, The American journal of surgical pathology.

[53]  Ximing J. Yang,et al.  Grading of Invasive Cribriform Carcinoma on Prostate Needle Biopsy: An Interobserver Study among Experts in Genitourinary Pathology , 2008, The American journal of surgical pathology.

[54]  Misop Han,et al.  Predicting 15-year prostate cancer specific mortality after radical prostatectomy. , 2011, The Journal of urology.

[55]  B. Donnelly,et al.  Whole gland primary prostate cryoablation: initial results from the cryo on-line data registry. , 2008, The Journal of urology.

[56]  Liang Cheng,et al.  Preoperative prediction of Gleason grade in radical prostatectomy specimens: the influence of different Gleason grades from multiple positive biopsy sites , 2005, Modern Pathology.

[57]  B. Delahunt,et al.  Gleason scoring: a comparison of classical and modified (International Society of Urological Pathology) criteria using nadir PSA as a clinical end point , 2010, Pathology.

[58]  Gleason Df Classification of prostatic carcinomas. , 1966 .

[59]  M. Kattan,et al.  Preoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy. , 2006, Journal of the National Cancer Institute.

[60]  H. Lee,et al.  Evaluation of concordance of Gleason score between prostatectomy and biopsies that show more than two different Gleason scores in positive cores. , 2006, Urology.

[61]  B. Trock,et al.  Tertiary Gleason patterns and biochemical recurrence after prostatectomy: proposal for a modified Gleason scoring system. , 2009, The Journal of urology.

[62]  A. Renshaw,et al.  PSA failure following definitive treatment of prostate cancer having biopsy Gleason score 7 with tertiary grade 5. , 2007, JAMA.

[63]  M. Kattan,et al.  Predicting the presence and side of extracapsular extension: a nomogram for staging prostate cancer. , 2004, The Journal of urology.

[64]  K. Hinnen,et al.  Predictors in the outcome of 125I brachytherapy as monotherapy for prostate cancer , 2011, Expert review of anticancer therapy.

[65]  W. Hellstrom,et al.  J Urol , 2014 .

[66]  B. Trock,et al.  An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011 , 2013, BJU international.

[67]  Jing Ma,et al.  Gleason score and lethal prostate cancer: does 3 + 4 = 4 + 3? , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[68]  B. Trock,et al.  Erratum: An updated prostate cancer staging nomogram (partin tables) based on cases from 2006 to 2011 (BJU International 111 (22-29)) , 2013 .

[69]  P. Spiess,et al.  Achieving the ‘bifecta’ using salvage cryotherapy for locally recurrent prostate cancer: analysis of the Cryo On‐Line Data (COLD) Registry data , 2012, BJU international.