Gleason Score: Understanding Prostate Cancer Grading
What is the Gleason Score?
The Gleason score is a grading system that ranges from 6 to 10, determined by adding the two most dominant cancer patterns seen on prostate biopsy, with higher scores indicating more aggressive disease that requires more intensive treatment. 1, 2
The pathologist assigns a grade from 1 (least aggressive) to 5 (most aggressive) based on the architectural differentiation of cancer cells, then combines the most predominant pattern with either the second most predominant pattern or the highest grade present to create the final score 3. When three grades are present, the highest grade and the dominant grade should be used 3.
Modern Grade Group Classification
The International Society of Urological Pathology introduced a simplified system that correlates directly with Gleason scores 2:
- Grade Group 1: Gleason ≤6 (well-formed glands only) 2
- Grade Group 2: Gleason 3+4=7 (predominantly well-formed glands) 2
- Grade Group 3: Gleason 4+3=7 (predominantly poorly formed glands) 2
- Grade Group 4: Gleason 8 (only poorly formed glands) 2
- Grade Group 5: Gleason 9-10 (no gland formation) 2
The distinction between Gleason 3+4=7 and 4+3=7 is critical—the predominant pattern 4 in 4+3=7 confers significantly worse prognosis. 4, 5
Risk Stratification Based on Gleason Score
Risk categories integrate Gleason score with PSA level and clinical stage 3, 1:
Very Low Risk
- Gleason ≤6, PSA <10 ng/mL, clinical stage T1c
- <3 biopsy cores positive, ≤50% cancer in each core
- PSA density <0.15 ng/mL/g
- 5-year biochemical recurrence-free survival: 96% 2
Low Risk
- Gleason ≤6, PSA <10 ng/mL, clinical stage T1-T2a
- 10-year prostate cancer-specific mortality on active surveillance: 2.4% 2
Intermediate Risk (Favorable)
- Gleason 3+4=7, PSA <10 ng/mL
- 5-year biochemical recurrence-free survival: 88% 2
Intermediate Risk (Unfavorable)
- Gleason 3+4=7 with PSA 10-20 ng/mL, OR Gleason 4+3=7 with PSA <20 ng/mL
- 5-year biochemical recurrence-free survival for Grade Group 3: 63% 2
High Risk
- Gleason 8-10, OR PSA >20 ng/mL, OR clinical stage T3-T4
- 5-year biochemical recurrence-free survival: 48% for Grade Group 4,26% for Grade Group 5 2
Treatment Recommendations for High Gleason Scores (8-10)
For patients with Gleason 8-10 (high-risk disease), aggressive definitive treatment is mandatory if life expectancy ≥5 years, consisting of either radical prostatectomy with pelvic lymph node dissection OR external beam radiation therapy plus 2-3 years of androgen deprivation therapy. 1, 4
Treatment Algorithm by Life Expectancy:
Life expectancy ≥5 years 1:
- Option 1: Radical prostatectomy with pelvic lymph node dissection 4
- Option 2: External beam radiation therapy (with or without brachytherapy) PLUS androgen deprivation therapy for 2-3 years 1, 4
Life expectancy <5 years 1:
- Observation is acceptable 1
Evidence for Treatment Selection
For Gleason 9-10 disease specifically, extremely dose-escalated radiotherapy (EBRT+brachytherapy) with ADT demonstrated superior systemic control compared to either standard EBRT or radical prostatectomy, with 5-year distant metastasis-free survival of 94.6% versus 78.7% for EBRT alone and 79.1% for surgery 6. All three modalities provided equivalent cancer-specific and overall survival 6.
Treatment for Intermediate Gleason Scores (7)
For Gleason 7 disease, treatment depends on the predominant pattern and life expectancy 1:
Life expectancy ≥10 years:
- Radical prostatectomy OR
- Radiation therapy (with or without brachytherapy; with or without hormone therapy for 4-6 months) 1
Life expectancy <10 years:
- Observation or treatment options are both acceptable 1
Critical caveat: Gleason 3+4=7 with otherwise favorable features may be eligible for active surveillance in selected patients with comorbidity or short life expectancy 7, but Gleason 4+3=7 behaves more aggressively and requires definitive treatment 5.
Treatment for Low Gleason Scores (≤6)
For Gleason ≤6 disease 1:
Life expectancy ≥10 years:
- Active surveillance OR definitive treatment (radical prostatectomy or radiation therapy) 1
Life expectancy <10 years:
- Active surveillance is appropriate 1
Essential Pathology Reporting Requirements
The pathology report must include 2, 4:
- Maximum length of cancer involvement in each core
- Most common and worst Gleason grades
- Extent of tumor involvement in each biopsy core
- Number of positive cores and percentage of involvement
- Presence of extraprostatic extension
Post-Treatment Monitoring
After radical prostatectomy, PSA should fall below detection level within 2 months 4. Consider adjuvant therapy if adverse pathological features are identified 4.