Gleason Score in Prostate Cancer
Clinical Significance of High Gleason Scores
A high Gleason score (8-10) indicates aggressive prostate cancer with significantly worse prognosis, requiring definitive treatment with radical prostatectomy or radiation therapy plus 2-3 years of androgen deprivation therapy in patients with life expectancy ≥5 years. 1, 2, 3
Understanding the Gleason Grading System
The Gleason score ranges from 6 to 10, calculated by adding the two most dominant cancer patterns identified microscopically, with each pattern graded 1-5. 4, 1 When three patterns are present, the highest grade and the dominant grade should be used. 4 With each increase in Gleason score, tumor aggressiveness increases proportionally. 4, 2
The modern Grade Group classification simplifies interpretation:
- Grade Group 1: Gleason ≤6 (well-formed glands only) 1
- Grade Group 2: Gleason 3+4=7 (predominantly well-formed glands) 1
- Grade Group 3: Gleason 4+3=7 (predominantly poorly-formed glands) 1
- Grade Group 4: Gleason 8 (only poorly-formed glands) 1
- Grade Group 5: Gleason 9-10 (no gland formation) 1
Prognostic Impact by Gleason Score
The distinction between Gleason 3+4=7 and 4+3=7 is critical, as the predominant pattern 4 in 4+3=7 confers significantly worse prognosis. 3, 5 Research demonstrates that Gleason 7 patients have worse outcomes than Gleason 5-6 (37% vs 63% 5-year biochemical control), and should never be grouped together for treatment planning. 5
Five-year biochemical recurrence-free survival after radical prostatectomy demonstrates the prognostic gradient:
- Grade Group 2 (Gleason 3+4=7): 88% 1
- Grade Group 3 (Gleason 4+3=7): 63% 1
- Grade Group 4 (Gleason 8): 48% 1
- Grade Group 5 (Gleason 9-10): 26% 1
The probability of dying from prostate cancer with Gleason ≥7 is 29%, rising to 48% for Gleason ≥8. 6
Risk Stratification Framework
Risk categories integrate Gleason score with PSA and clinical stage to guide treatment:
Low Risk: Gleason ≤6, PSA <10 ng/mL, clinical stage T1-T2a (10-year prostate cancer-specific mortality 2.4% on active surveillance) 1
Intermediate Risk (Favorable): Gleason 3+4=7, PSA <10 ng/mL 1
Intermediate Risk (Unfavorable): Gleason 3+4=7 with PSA 10-20 ng/mL, OR Gleason 4+3=7 with PSA <20 ng/mL 1
High Risk: Gleason 8-10, OR PSA >20 ng/mL, OR clinical stage T3-T4 4, 1
Treatment Recommendations by Gleason Score
Gleason ≤6 (Low Risk)
Active surveillance is appropriate for life expectancy <10 years; observation or definitive treatment for ≥10 years. 2 Treatment options include radical prostatectomy or radiation therapy. 2 The modified Gleason score (proportion of grades 4 and 5) helps identify true low-risk patients eligible for active surveillance. 4, 7
Gleason 7 (Intermediate Risk)
Observation is acceptable only if life expectancy <10 years; definitive treatment is recommended for ≥10 years. 2 Options include radical prostatectomy or radiation therapy with or without brachytherapy, with or without 4-6 months of hormone therapy. 2
Critical caveat: Gleason 4+3=7 with extensive biopsy involvement (e.g., 12/18 cores positive) shifts patients toward high-risk category requiring more aggressive treatment. 3
Gleason 8-10 (High Risk)
Observation is appropriate only if life expectancy <5 years; aggressive definitive treatment is mandatory for ≥5 years. 2, 3
Primary treatment options:
- Radical prostatectomy with pelvic lymph node dissection (provides precise pathological staging and guides adjuvant therapy decisions) 3
- External beam radiation therapy plus 2-3 years of androgen deprivation therapy 2, 3
- External beam radiation therapy plus brachytherapy with or without androgen deprivation therapy 2
Post-Surgical Management
After radical prostatectomy, consider adjuvant therapy if adverse pathological features are identified (positive margins, seminal vesicle invasion, extracapsular extension). 3 Options include observation with early salvage radiation, adjuvant radiation therapy, or adjuvant androgen deprivation therapy with or without radiation. 3
PSA should fall below detection level within 2 months post-prostatectomy, with regular monitoring essential for detecting biochemical recurrence. 3
Essential Pathology Reporting Requirements
The pathology report must specify: biopsy core length in millimeters, tumor involvement length or percentage, Gleason score with proportion of grades 4 and 5, number and percentage of positive cores, and presence of extraprostatic extension. 4, 1 The Gleason score of tumor at surgical margins is an independent predictor of biochemical recurrence and should be routinely reported. 8
Common Pitfalls
Upgrading from biopsy to prostatectomy occurs frequently: 65% of Gleason 6 cases upgrade to 7a, and 19% upgrade to 7b at final pathology. 7 This underscores the importance of comprehensive biopsy sampling and careful patient selection for active surveillance.
Tumor grade should not be assessed after radiotherapy or hormonal therapy, as these treatments alter histologic appearance. 4