Gleason score indicates the grade or “aggressiveness” of your prostate cancer (prostate adenocarcinoma). The higher the Gleason score, the more aggressive the cancer is likely to be and more difficult to cure 1). The Gleason scoring system is based on the microscopic arrangement, architecture or pattern of the glands in prostate cancer biopsy samples rather than on the individual cellular characteristics that define most other cancers. The Gleason score is calculated based on the dominant histologic grades, from grade 1 (well differentiated, representing an almost normal microscopic glandular pattern and appearance) to grade 5 (very poorly differentiated where no glandular architecture remains, and there are only sheets of abnormal cancer cells) 2). The classical Gleason score is derived by adding the two most prevalent pattern grades, yielding a score ranging from 2 to 10. Because there is some evidence that the least-differentiated component of the specimen may provide independent prognostic information, the score is often provided by its separate components (e.g., Gleason score 3 + 4 = 7 versus 4 + 3 = 7) 3). The Gleason prostate cancer score has been shown, over time, to be the most reliable and predictive histological grading system available 4). Originally developed by pathologist Dr. Donald Gleason in the 1960s, it has stood the test of time and has been universally adopted for all prostate cancer pathological descriptions 5).
For most kinds of cancer, tumor grade is determined by looking at individual cancer cells through a microscope using a high level of magnification to examine the details of those cells. Gleason score is different. With this method, a pathologist examines prostate tissue samples under a microscope using low magnification to observe the patterns of the cancer cells.
Each pattern is given a number, usually 3, 4, or 5. Because many prostate cancers contain more than one pattern, the two most common patterns are added together to make the Gleason score. If the patterns are very similar or if only one pattern is found, then the cancer is given two of the same number.
A prostate cancer biopsy also differs from other forms of cancer in the number of samples a pathologist examines. Rather than just one or two tissue samples, 12 samples are usually taken for a prostate biopsy. Of those samples, some may have different Gleason scores. If that’s the case, the pathologist assigns the highest score observed.
It is worth noting, however, that if only one or two of the samples have a score of 8 and the others are lower, or if some do not show evidence of cancer at all, then the outlook is better than if nine or ten samples are at 8. Your doctor will take that into account when evaluating the outlook for your cancer.
Your pathologist also will review the amount or percentage of cancer found in each sample. If the percentage is low, the overall outlook is better than if the percentage of cancerous tissue is high in the samples.
The Gleason score always contains two grades in the form of numbers and then a total score:
- The predominant Gleason grade pattern is always the first number, 1 to 5, and
- The second number would be any secondary or minor pattern, also graded 1 to 5.
So the absolute best and lowest risk Gleason score would be Gleason 1 + 1 = 2, and the worst high-grade pathology would be Gleason 5 + 5 = 10. In real life, these histological extremes are almost never seen 6).
If only one Gleason grade or pattern is seen, then the Gleason score would consist of the same Gleason grade repeated and added together as in Gleason 3 + 3 = 6; which happens to be the most commonly found Gleason score 7).
- Low-grade tumors would be any Gleason score of 3 + 3 = 6 or less 8).
- Intermediate-grade cancers would be a Gleason score of 3 + 4 = 7. This would mean that most of the tumor was Gleason grade 3, but there was a smaller portion that was the more aggressive Gleason grade 4 9).
- A Gleason score of 4 + 3 = 7 or higher would be considered high-grade cancer 10).
Of the factors related to prostate cancer that doctors take into consideration when deciding on treatment, Gleason score is probably the most important one. The Gleason score will help your doctor understand if the cancer is as a low-, intermediate- or high-risk disease. Generally, Gleason scores of 6 are treated as low risk cancers. Gleason scores of around 7 are treated as intermediate/mid-level cancers. There are two types of these scores. A 4+3 tumor is more aggressive than a 3+4 tumor. That’s because more of the higher aggressive grade tumor was found. Gleason scores of 8 and above are treated as high-risk cancers. Gleason 8, 9 and 10 tumors are the most aggressive. Some of these high-risk tumors may have already spread by the time they are found. Talk to your health care provider about your Gleason score.
In most cases, treatment with radiation and hormonal therapy or with surgery is recommended based on a total Gleason score of 8. Gleason score of 8 likely came from two very similar patterns of 4 and 4. In some cases, a score of 8 may come from a pattern of 5 and 3 or 3 and 5, but those are not common. The first number identifies the primary pattern, or the one seen most predominately in the sample. The second number is the secondary pattern, or one that is visible but not as widespread as the primary pattern.
Generally, with a Gleason score of 8 or higher, treatment is recommended, as long as you do not have other medical problems that would make it hard for you to have radiation and hormonal therapy or surgery. Depending on age and the specific numbers that make up the Gleason score, men who have scores of 6 or 7 may not need immediate treatment. Instead, their doctors may suggest a program of active surveillance to monitor the cancer and to see if it progresses.
Before treatment begins in patients who have higher Gleason scores, most doctors suggest imaging exams such as bone and CT scans or MRI studies of the pelvis and abdomen. This allows your doctor to see if the cancer has spread beyond the prostate and will help your doctor recommend which treatment options are best for you.
Futhermore, there is evidence that, over time, pathologists have tended to award higher Gleason scores to the same histologic patterns, a phenomenon sometimes termed grade inflation 11). This phenomenon complicates comparisons of outcomes in current versus historical patient series. For example, prostate biopsies from a population-based cohort of 1,858 men diagnosed with prostate cancer from 1990 through 1992 were re-read in 2002 to 2004 12). The contemporary Gleason score readings were an average of 0.85 points higher (95% confidence interval, 0.79–0.91; P < .001) than the same slides read a decade earlier. As a result, Gleason-score standardized prostate cancer mortality rates for these men were artifactually improved from 2.08 to 1.50 deaths per 100-person years—a 28% decrease even though overall outcomes were unchanged 13).
While architecture or pattern, as described by the Gleason score, is certainly a major component of the histological diagnosis of prostate cancer, it is not the only criteria. For example, prostate specific membrane antigen is a transmembrane carboxypeptidase that exhibits folate hydrolase activity which is overexpressed in prostate cancer tissues. Its presence would suggest prostate cancer 14).
Other significant microscopic histological features and indicators of prostate cancer would include 15):
- Infiltrative glandular growth pattern
- Absence of a basal cell layer
- Atypically enlarged cell nuclei with large nucleoli
- Increased mitotic figures
- Intraluminal wispy blue mucin
- Pink amorphous secretions
- Intraluminal crystalloids
- Adjacent High-Grade Prostatic Intraepithelial Neoplasia (High-Grade PIN)
- Amphophilic cytoplasm
The number of positive biopsies also has prognostic value. In a study of 960 intermediate grade (Gleason 3 + 4 = 7) prostate cancers followed for at least four years, 86% of patients with less than 34% positive biopsies demonstrated a stable PSA compared with only 11% of patients who had more than 50% positive biopsies.
Cancer volume is another important prognostic parameter, but it is difficult to measure accurately with available technology. Prostatic MRI is currently our best instrumentation for estimating tumor volume 16).
Perineural invasion is somewhat helpful in predicting extracapsular tumor extension and may be associated with slightly higher tumor aggressiveness, but studies are conflicting on its clinical usefulness 17).
Figure 1. Gleason score
New Gleason Scoring System
In 2016, the World Health Organization (WHO) proposed a new classification system based on clinical experience with the old Gleason scoring system that suggested very little difference in clinical outcomes in lower Gleason score patients, but somewhat different ones in the higher grades. The following is a summary of the “New” Gleason system 18):
- Grade group 1 (Gleason score less than or equal to 6): Only individual discrete well-formed glands
- Grade group 2 (Gleason score 3 + 4 = 7): Predominantly well-formed glands with a lesser component of poorly-formed, fused or cribriform glands
- Grade group 3 (Gleason score 4 + 3 = 7): Predominantly poorly-formed, fused, or cribriform glands with a lesser component of well-formed glands
- Grade group 4 (Gleason score 8): Only poorly-formed/fused/cribriform glands; or predominantly well-formed glands with a lesser component lacking glands; or predominantly lacking glands with a lesser component of well-formed glands
- Grade group 5 (Gleason scores 9 or 10): Lacks gland formation (or with necrosis) with or without poorly-formed, fused or cribriform glands
In clinical practice, group 1 is considered “low grade,” Group 2 is “intermediate grade,” and group 3 or higher is “high grade” disease 19).
Gleason score prostate cancer prognosis
Prostate cancer with Gleason score 7 from 4+3 had worse overall survival and cancer-specific survival than Gleason score 7 from 3+4 20). Previous studies confirmed the significant difference in biochemical recurrence-free survival following radical prostatectomy between Gleason score 3+4 and 4+3 21). In a study of 263 men with pathological Gleason 7 tumor after radical prostatectomy and a median follow-up of 6.7 years, patients with Gleason score 4+3 were more likely to have seminal vesicle involvement, a higher pathological stage, extraprostatic extension, and higher median preoperative PSA, whereas the score was not independently associated with progression-free survival 22). Sakr et al. 23) found that patients with Gleason score 4+3 had a significantly higher incidence of biochemical recurrence than those with Gleason score 3+4 in the subset of patients with organ-confined prostate cancer. Chan et al. 24) investigated 570 cases of Gleason score 7 prostate cancer without lymph node metastasis, seminal vesicle invasion, or tertiary Gleason pattern, and found that a Gleason score of 4+3 was predictive of metastatic disease compared with a Gleason score of 3+4. Alenda et al. 25) found that primary Gleason pattern 4 is an independent predictor of PSA failure based on a single-center cohort of 1,248 patients with Gleason 7 tumors. Miyake et al. 26) evaluated the significance of the primary Gleason pattern in 959 consecutive Japanese male patients with Gleason score 7 prostate cancer treated with radical prostatectomy and showed that primary Gleason pattern 4 is significantly associated with the biochemical outcome.
Regarding prostate cancer associated mortality, Stark et al. 27) reported that Gleason score 4+3 is associated with a 3-fold increase in lethal prostate cancer compared with Gleason score 3+4. In this study 28), a large cohort of patients from the Surveillance, Epidemiology, and End Results (SEER) database and a long follow-up time were used to investigate the effects of Gleason score 3+4 and 4+3 on the overall survival and cancer-specific survival of prostate cancer. Gleason score 4+3 was associated with worse overall survival and cancer-specific survival than Gleason score 3+4 in prostate cancer patients in the multivariate Cox regression analysis and in propensity score matching analysis with other confounding factors excluded.
References [ + ]
|1.||↵||Zelefsky MJ, Eastham JA, Sartor AO: Cancer of the prostate. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1220-71.|
|2.||↵||Gleason DF, Mellinger GT. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J. Urol. 1974 Jan;111(1):58-64.|
|3.||↵||Chan TY, Partin AW, Walsh PC, et al.: Prognostic significance of Gleason score 3+4 versus Gleason score 4+3 tumor at radical prostatectomy. Urology 56 (5): 823-7, 2000.|
|4, 19.||↵||Leslie SW, Soon-Sutton TL, Sajjad H, et al. Prostate Cancer. [Updated 2019 Oct 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470550|
|5.||↵||Montironi R, Santoni M, Mazzucchelli R, Burattini L, Berardi R, Galosi AB, Cheng L, Lopez-Beltran A, Briganti A, Montorsi F, Scarpelli M. Prostate cancer: from Gleason scoring to prognostic grade grouping. Expert Rev Anticancer Ther. 2016;16(4):433-40.|
|6, 8, 10.||↵||Pierorazio PM, Walsh PC, Partin AW, Epstein JI. Prognostic Gleason grade grouping: data based on the modified Gleason scoring system. BJU Int. 2013 May;111(5):753-60.|
|7.||↵||Epstein JI, Amin MB, Reuter VE, Humphrey PA. 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. 2017 Apr;41(4):e1-e7|
|9.||↵||Pan CC, Potter SR, Partin AW, Epstein JI. The prognostic significance of tertiary Gleason patterns of higher grade in radical prostatectomy specimens: a proposal to modify the Gleason grading system. Am. J. Surg. Pathol. 2000 Apr;24(4):563-9.|
|11.||↵||Thompson IM, Canby-Hagino E, Lucia MS: Stage migration and grade inflation in prostate cancer: Will Rogers meets Garrison Keillor. J Natl Cancer Inst 97 (17): 1236-7, 2005.|
|12.||↵||Albertsen PC, Hanley JA, Barrows GH, et al.: Prostate cancer and the Will Rogers phenomenon. J Natl Cancer Inst 97 (17): 1248-53, 2005.|
|13.||↵||PDQ Adult Treatment Editorial Board. Prostate Cancer Treatment (PDQ®): Health Professional Version. 2019 Sep 20. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK66036|
|14.||↵||Evans JC, Malhotra M, Cryan JF, O’Driscoll CM. The therapeutic and diagnostic potential of the prostate specific membrane antigen/glutamate carboxypeptidase II (PSMA/GCPII) in cancer and neurological disease. Br. J. Pharmacol. 2016 Nov;173(21):3041-3079.|
|15.||↵||Shen MM, Abate-Shen C. Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev. 2010 Sep 15;24(18):1967-2000.|
|16.||↵||Liu L, Tian Z, Zhang Z, Fei B. Computer-aided Detection of Prostate Cancer with MRI: Technology and Applications. Acad Radiol. 2016 Aug;23(8):1024-46.|
|17.||↵||Azam SH, Pecot CV. Cancer’s got nerve: Schwann cells drive perineural invasion. J. Clin. Invest. 2016 Apr 01;126(4):1242-4.|
|18.||↵||Chen N, Zhou Q. The evolving Gleason grading system. Chin. J. Cancer Res. 2016 Feb;28(1):58-64.|
|20, 28.||↵||Zhu X, Gou X, Zhou M. Nomograms Predict Survival Advantages of Gleason Score 3+4 Over 4+3 for Prostate Cancer: A SEER-Based Study. Front Oncol. 2019;9:646. Published 2019 Jul 16. doi:10.3389/fonc.2019.00646 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646708|
|21.||↵||Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi-Galluzzi C, et al. . A contemporary prostate cancer grading system: a validated alternative to the gleason score. Eur Urol. (2016) 69:428–35. 10.1016/j.eururo.2015.06.046|
|22.||↵||Lau WK, Blute ML, Bostwick DG, Weaver AL, Sebo TJ, Zincke H. Prognostic factors for survival of patients with pathological Gleason score 7 prostate cancer: differences in outcome between primary Gleason grades 3 and 4. J Urol. (2001) 166:1692–7. 10.1016/S0022-5347(05)65655-8|
|23.||↵||Sakr WA, Tefilli MV, Grignon DJ, Banerjee M, Dey J, Gheiler EL, et al. . Gleason score 7 prostate cancer: a heterogeneous entity? Correlation with pathologic parameters and disease-free survival. Urology. (2000) 56:730–4. 10.1016/S0090-4295(00)00791-3|
|24.||↵||Chan TY, Partin AW, Walsh PC, Epstein JI. Prognostic significance of Gleason score 3+4 versus Gleason score 4+3 tumor at radical prostatectomy. Urology. (2000) 56:823–7. 10.1016/S0090-4295(00)00753-6|
|25.||↵||Alenda O, Ploussard G, Mouracade P, Xylinas E, de la Taille A, Allory Y, et al. . 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. (2011) 29:671–6. 10.1007/s00345-010-0620-9|
|26.||↵||Miyake H, Muramaki M, Furukawa J, Tanaka H, Inoue TA, Fujisawa M. Prognostic significance of primary Gleason pattern in Japanese men with Gleason score 7 prostate cancer treated with radical prostatectomy. Urol Oncol. (2013) 31:1511–6. 10.1016/j.urolonc.2012.05.001|
|27.||↵||Stark JR, Perner S, Stampfer MJ, Sinnott JA, Finn S, Eisenstein AS, et al. . Gleason score and lethal prostate cancer: does 3 + 4 = 4 + 3? J Clin Oncol. (2009) 27:3459–64. 10.1200/JCO.2008.20.4669|