Gleason Scoring System for Prostate Cancer
The Gleason score is a histopathologic grading system ranging from 6 to 10 that predicts prostate cancer aggressiveness by adding the two most dominant cancer patterns (each graded 1-5) identified by a pathologist examining biopsy tissue under microscopy, with higher scores indicating more aggressive disease and worse prognosis. 1, 2
How the Score is Calculated
A pathologist examines prostate biopsy tissue and assigns grades from 1 (most differentiated, least aggressive) to 5 (least differentiated, most aggressive) based on how much the cancer cells deviate from normal prostate architecture. 2, 3
The final Gleason score is calculated by adding the primary grade (most common pattern) and the secondary grade (second most common pattern). 2
When three grades are present, the score combines the most predominant pattern with the highest grade present, not necessarily the second most common pattern. 2, 3
Example: A tumor with 60% grade 3,35% grade 4, and 5% grade 5 is reported as Gleason 3+4=7 with tertiary grade 5. 2
For cases with >95% poorly formed/fused/cribriform glands or lack of glands, the component of <5% well-formed glands is not factored into the grade. 1
Contemporary Grade Group System
The International Society of Urological Pathology introduced a simplified Grade Group classification that directly correlates with Gleason scores and provides clearer prognostic stratification: 1, 4
Grade Group 1: Gleason score ≤6 (only individual discrete well-formed glands) 1, 4
Grade Group 2: Gleason score 3+4=7 (predominantly well-formed glands with lesser component of poorly formed/fused/cribriform glands) 1, 4
Grade Group 3: Gleason score 4+3=7 (predominantly poorly formed/fused/cribriform glands with lesser component of well-formed glands) 1, 4
Grade Group 4: Gleason score 8 (patterns 4+4,3+5, or 5+3; only poorly formed/fused/cribriform glands or mixed patterns) 1, 2
Grade Group 5: Gleason score 9-10 (lack of gland formation with or without necrosis) 1, 4
Prognostic Significance and Clinical Outcomes
The Grade Group system has been validated in cohorts exceeding 26,000 patients and demonstrates clear prognostic separation: 1
Grade Group 1: 96% 5-year biochemical recurrence-free survival after radical prostatectomy 1, 4
Grade Group 2: 88% 5-year biochemical recurrence-free survival 1, 4
Grade Group 3: 63% 5-year biochemical recurrence-free survival 1, 4
Grade Group 4: 48% 5-year biochemical recurrence-free survival 1, 4
Grade Group 5: 26% 5-year biochemical recurrence-free survival 1, 4
Each incremental increase in Gleason score is directly associated with greater tumor aggressiveness, higher risk of metastasis, and increased prostate cancer-specific mortality. 2, 4
Integration into Risk Stratification
Gleason grade, combined with PSA level and clinical stage, defines prostate cancer risk categories that guide treatment decisions: 1, 2
Low Risk: Gleason ≤6 (Grade Group 1), PSA <10 ng/mL, clinical stage T1-T2a 1, 4
Intermediate Risk: Gleason 7 (Grade Groups 2-3) OR PSA 10-20 ng/mL OR clinical stage T2b-c 1, 4
High Risk: Gleason 8-10 (Grade Groups 4-5) OR PSA >20 ng/mL OR clinical stage T3-T4 1, 4
Essential Pathology Reporting Requirements
Comprehensive pathology reports must document: 2, 3
The Gleason score (sum of the two dominant grades) 2
The proportion of Gleason grades 4 and 5 (modified Gleason score) 2
Number and anatomical location of positive cores 2
Presence or absence of extraprostatic extension 2
Critical Caveats
Do not perform Gleason grading on specimens from patients who have received radiotherapy or hormonal therapy, as treatment-induced changes obscure the original differentiation pattern and render grading unreliable. 2
Cribriform and glomeruloid glands are always assigned Gleason pattern 4, regardless of morphology. 5
In cases with borderline morphology between pattern 3 and 4 with crush artifacts, favor the lower grade. 5
The modified Gleason score (percentage of grade 4-5 disease) provides additional prognostic information beyond the standard score. 2