Aging like a fine wine
Few things in science stand the test of time. Among urological cancers, perhaps more than any other tumor type, this is especially true of prostate cancer. When it comes to prostate cancer, very little can withstand microscopic examination and scientific challenges over decades. So, as we celebrate 50 years of success, the Gleason rating system deserves recognition.
Donald Gleason, MD, PhD, devised the “Gleason Score” in the 1960s while employed by the Minneapolis VA Health Care System. He first published his findings in 1966 based on the evaluation of glandular patterns of cancer present in prostate tissue.1.2
The grading system was modified by Gleason and the Veterans Administration Cooperative Urological Research Group and some additional improvements were made in the mid-1970s.3 The grading system is based on the histological pattern of the arrangement of carcinoma cells in sections stained with hematoxylin and eosin (H&E). The score is presented as the sum of the dominant model and the largest minority model present in the sample. Five basic grade patterns are used to generate a histological score, which can range from 2 to 10, with the highest pattern/score representing less differentiated tumours.
We have learned the power of this scoring system over the years. The increase in Gleason grade is directly related to several pathological parameters, including tumor size, margin status, and pathological stage. Indeed, models have been developed that predict disease stage prior to treatment based on Gleason grade by needle biopsy, total level of serum prostate-specific antigen, and clinical stage.4 Gleason grade has also been linked to several clinical parameters, including clinical stage, progression to metastatic disease, and overall survival. Gleason grade is often incorporated into nomograms used to predict response to treatment, including radiation therapy and surgery.5
Along the way, additional improvements in the Gleason ranking have been implemented. In 2005, the International Society of Urological Pathology recommended against using Models 1 and 2, resulting in an abbreviated grading scale of 6 to 10.6 In addition, the consensus recommended that several variant patterns previously classified as 3 and all cribriform patterns be classified as pattern 4. Gleason 3+4 and 4+3. This has led to both improved prognostic accuracy and difficulty in comparing historical and contemporary results.
These changes, for the most part, led to improved prognostic accuracy. Yet, due to the complexity of reporting prognostic results on a 6–10 scoring scale, a new scoring scheme was proposed which consisted of score groups (GGs).7 This has been proposed to communicate biological aggressiveness and to guide clinical management. These prognostic grading groups use a scale of 1 to 5, with GG1 consisting of Gleason 3+3, GG2 (Gleason 3+4), GG3 (Gleason 4+3), GG4 (Gleason 4+4) and GG5 (Gleason 4 +5, 5+4 and 5+5). This new modified Gleason grade group classification has been validated to be correlated with cancer-specific mortality.
The Gleason Grading System and its subsequent modifications have been used worldwide by interdisciplinary teams for the past 50 years to aid in the treatment of men with prostate cancer. Undoubtedly, the Gleason ranking system will continue to be refined. A debate that has recently resurfaced is a decade-old argument that a Gleason score 6 (GG1) tumor should not be called cancer.8 Admittedly, this is a controversial topic that has supporters and detractors, but it reinforces the idea that the Gleason grading system remains relevant and that modernizing the nomenclature will only enhance its value.
So, as we turn to additional tools such as genetic profiling, molecular staining, biomarkers, and artificial intelligence, we will find more accurate tools to improve our prognostic capabilities. However, I predict that for the foreseeable future, the H&E-dependent Gleason grading system will retain a prominent place in the treatment of men with prostate cancer. Dr. Gleason passed away in 2009, but his grading system lives on and, like fine wine, improves over time. Thank you, Dr. Gleason, for your insightful observations all those years ago. The Gleason Grading System has helped us treat (and not treat) millions of men and will continue to be a prognostic staple in our toolbox.
Cookson is a professor at the University of Oklahoma Health Sciences Center, where he also serves as chair of the Department of Urology. He is also Chief of Urologic Oncology at Stephenson Cancer Center and President of the Society of Urologic Oncology and the South Central Chapter of the American Urological Association.
1.Gleason DF. Classification of prostatic carcinomas. Cancer Chemotherapy Representative 1966;50(3):125-128.
2. Bailar JC 3rd, Mellinger GT, Gleason DF. Survival rates of prostate cancer patients, tumor stage and differentiation – preliminary report. Cancer Chemotherapy Representative1966;50(3):129-136.
3. Gleason DF. Histological grading and staging of prostate cancer. In: Tannenbaum M, ed. Urological pathology: the prostate. Lea and Feibiger; 1971:171.
4. Partin AW, Mangold LA, Lamm DM, Walsh PC, Epstein JI, Pearson JD. Contemporary update of prostate cancer staging nomograms (Partin tables) for the new millennium. Urology. 2001;58(6):843-848. doi:10.1016/s0090-4295(01)01441-8
5. Kattan MW, Scardino PT. Progression prediction: clinically useful nomograms. Clin Prostate cancer. 2002;1(2):90-96. doi:10.3816/cgc.2002.n.010
6. Epstein JI, Allsbrook WC Jr, Amin MB, Egevad LL; ISUP Ranking Commission. The 2005 International Society of Urological Pathology (ISUP) consensus conference on the Gleason classification of prostatic carcinoma. Am J Surg Pathol. 2005;29(9):1228-1242.doi:10.1097/01.pas.0000173646.99337.b1
7. Epstein JI, Egevad L, Amin MB, et al; Ranking committee. The 2014 International Society of Urological Pathology (ISUP) consensus conference on the Gleason classification of prostate cancer: defining classification models and proposing a new classification system. Am J Surg Pathol. 2016;40(2):244-252.doi:10.1097/PAS.0000000000000530
8. Carter HB, Partin AW, Walsh PC, et al. Gleason score 6 adenocarcinoma: should it be labeled as cancer? J Clin Oncol. 2012;30(35):4294-4296. doi:10.1200/JCO.2012.44.0586