The Significance of Gleason Scoring in Prostate Cancer Treatment Decisions
Gleason scoring is a critical determinant in risk stratification for prostate cancer that directly guides treatment decisions based on tumor aggressiveness, with higher scores indicating more aggressive disease requiring more intensive treatment approaches. 1
Understanding the Gleason Scoring System
The Gleason grading system evaluates the architectural pattern of prostate cancer cells, assigning grades from 1 (least aggressive) to 5 (most aggressive) based on the degree of differentiation:
- The Gleason score represents the sum of the two most predominant histological patterns observed in the prostate tissue sample 2, 1
- The order of patterns is significant - a 4+3=7 score carries a worse prognosis than a 3+4=7 score 1
- Scores range from 2-10, though scores 2-4 are uncommon in clinical practice 2
In 2014, the International Society of Urological Pathology (ISUP) developed a new prostate cancer grading system that assigns Grade Groups 1-5, derived from the Gleason score 2:
- Grade Group 1: Gleason score ≤6 (well-formed glands)
- Grade Group 2: Gleason score 3+4=7 (predominantly well-formed glands with lesser component of poorly formed glands)
- Grade Group 3: Gleason score 4+3=7 (predominantly poorly formed glands with lesser component of well-formed glands)
- Grade Group 4: Gleason score 8 (various patterns)
- Grade Group 5: Gleason score 9-10 (lack of gland formation)
Role in Risk Stratification
Gleason scoring is a fundamental component of risk classification systems that guide treatment decisions 2, 1:
Low-risk disease:
- Gleason score ≤6 (Grade Group 1)
- PSA <10 ng/mL
- Clinical stage T1-T2a
Intermediate-risk disease:
- Further subdivided into favorable and unfavorable categories 2
- Favorable intermediate risk: Grade Group 2 (Gleason 3+4=7) with PSA <10 ng/mL
- Unfavorable intermediate risk: Grade Group 2 with PSA 10-20 ng/mL or Grade Group 3 (Gleason 4+3=7) with PSA <20 ng/mL
High-risk disease:
- Gleason score 8-10 (Grade Groups 4-5)
- PSA >20 ng/mL
- Clinical stage T2c or higher
Impact on Treatment Decisions
The Gleason score significantly influences treatment recommendations 2, 1:
Very low/low-risk disease (Gleason ≤6):
- For patients with life expectancy <10 years: Observation (active surveillance) is recommended
- For patients with life expectancy ≥10 years: Options include observation, radical prostatectomy, external beam radiation therapy, or brachytherapy
Intermediate-risk disease (Gleason 7):
- For patients with life expectancy <10 years: Observation or treatment options including radical prostatectomy or radiation therapy (with or without short-term hormone therapy)
- For patients with life expectancy ≥10 years: Radical prostatectomy or radiation therapy (with or without short-term hormone therapy)
High-risk disease (Gleason 8-10):
- For patients with life expectancy <5 years: Observation may be appropriate
- For patients with life expectancy ≥5 years: Radical prostatectomy or radiation therapy (with or without brachytherapy; typically with 2-3 years of hormone therapy)
Prognostic Value
The Gleason score has been validated as a strong predictor of clinical outcomes 2, 3:
- In a large validation study, 5-year biochemical recurrence-free progression probabilities after radical prostatectomy for Grade Groups 1 through 5 were 96%, 88%, 63%, 48%, and 26%, respectively 2
- Higher Gleason grades correlate with increased risk of disease progression, metastasis, and prostate cancer-specific mortality 4, 3
Clinical Considerations and Limitations
- Discordance between biopsy and radical prostatectomy Gleason scores occurs in approximately 50% of cases, with upgrading being more common than downgrading 5, 6
- Smaller prostate volume and higher PSA density are predictors for upgrading in patients with biopsy Gleason score ≤6 6
- Tertiary patterns (small components of higher-grade disease) may behave more aggressively than the primary score would suggest 1
- New biomarkers and proteomic signatures are being developed to better stratify intermediate-risk patients (Gleason 7), who can harbor either aggressive or indolent disease 7
The Gleason score remains one of the most reliable prognostic indicators in prostate cancer and is essential for guiding appropriate treatment selection to optimize patient outcomes while avoiding unnecessary treatment-related morbidity.