What is the significance of the Gleason score in prostate cancer diagnosis and treatment?

Understanding the Gleason Score in Prostate Cancer

The Gleason score is the single most critical histopathologic predictor of prostate cancer aggressiveness, ranging from 6 to 10, where higher scores indicate more aggressive disease and directly determine treatment strategy and prognosis. 1

How the Gleason Score is Determined

• A pathologist examines prostate biopsy tissue under a microscope and identifies the two most dominant cancer patterns, each graded from 1 to 5 based on how much the cancer cells differ from normal prostate tissue 2
• The two most common patterns are added together to create the final Gleason score, though tumors with a tertiary Gleason grade 4 or 5 behave more aggressively than the sum of the two dominant patterns alone 1
• The scoring system is based entirely on the histologic pattern of arrangement of carcinoma cells in H&E-stained sections 3

Modern Grade Group Classification System

The International Society of Urological Pathology introduced a simplified Grade Group system that directly correlates with Gleason scores and enables patients to better understand their true risk level 4, 1:

• Grade Group 1: Gleason score ≤6 (only individual discrete well-formed glands) 4
• Grade Group 2: Gleason score 3+4=7 (predominantly well-formed glands with lesser component of poorly formed/fused/cribriform glands) 4
• Grade Group 3: Gleason score 4+3=7 (predominantly poorly formed/fused/cribriform glands with lesser component of well-formed glands) 4
• Grade Group 4: Gleason score 4+4=8 (only poorly formed/fused/cribriform glands or mixed patterns) 4
• Grade Group 5: Gleason score 9-10 (lack of gland formation with or without necrosis) 4

However, recent evidence demonstrates that Gleason scores provide more accurate prognostic information than Grade Groups, as significant prognostic heterogeneity exists within Grade Groups 4 and 5 that is lost when scores are collapsed into these broader categories. 5

Prognostic Significance and Survival Outcomes

The Gleason score directly predicts biochemical recurrence-free survival after radical prostatectomy 4:

• Grade Group 1 (Gleason ≤6): 96% 5-year biochemical recurrence-free survival 4
• Grade Group 2 (Gleason 3+4=7): 88% 5-year biochemical recurrence-free survival 4
• Grade Group 3 (Gleason 4+3=7): 63% 5-year biochemical recurrence-free survival 4
• Grade Group 4 (Gleason 8): 48% 5-year biochemical recurrence-free survival 4
• Grade Group 5 (Gleason 9-10): 26% 5-year biochemical recurrence-free survival 4

The distinction between Gleason 3+4=7 and 4+3=7 is clinically critical, as the predominant pattern 4 in 4+3=7 confers significantly worse prognosis. 6

Risk Stratification Framework

The NCCN Guidelines integrate Gleason score with PSA level and clinical stage to assign patients to risk groups that guide treatment selection 4, 1:

Very Low Risk

• Clinical stage T1c, Gleason score ≤6, PSA <10 ng/mL, <3 biopsy cores positive, ≤50% cancer in each core, PSA density <0.15 ng/mL/g 1
• 5-year biochemical recurrence-free survival: 96% 1

Low Risk

• Clinical stage T1-T2a, Gleason score ≤6, PSA <10 ng/mL 1
• 10-year prostate cancer-specific mortality on active surveillance: 2.4% 1

Intermediate Risk (Favorable)

• Gleason score 3+4=7, PSA <10 ng/mL 1
• 5-year biochemical recurrence-free survival: 88% 1

Intermediate Risk (Unfavorable)

• Gleason score 3+4=7 with PSA 10-20 ng/mL, OR Gleason score 4+3=7 with PSA <20 ng/mL 1
• 5-year biochemical recurrence-free survival: 63% 1

High Risk

• Clinical stage T3-T4, OR Gleason score 8-10, OR PSA >20 ng/mL 1
• 5-year biochemical recurrence-free survival: 48% for Grade Group 4,26% for Grade Group 5 1

Treatment Recommendations Based on Gleason Score

Gleason ≤6 (Low Risk)

• Life expectancy <10 years: Observation is appropriate 2
• Life expectancy ≥10 years: Active surveillance, radical prostatectomy, or radiation therapy 2

Gleason 7 (Intermediate Risk)

• Life expectancy <10 years: Observation or treatment options 2
• Life expectancy ≥10 years: Radical prostatectomy or radiation therapy (with or without brachytherapy; with or without hormone therapy for 4-6 months) 2

Gleason 8-10 (High Risk)

• Life expectancy <5 years: Observation only 2
• Life expectancy ≥5 years: Radical prostatectomy with pelvic lymph node dissection, or external beam radiation therapy plus androgen deprivation therapy for 2-3 years 2, 6

Critical Pathology Reporting Requirements

The pathology report must include 1, 6:

• Maximum length of cancer involvement in each core
• The most common and worst Gleason grades
• Extent of tumor involvement in each biopsy core
• Number of positive cores and percentage of involvement
• Proportion of Gleason grades 4 and 5
• Presence of extraprostatic extension

Important Clinical Caveats

Given a Gleason score of 7 or greater, the probability of dying of prostate cancer is 29%, and for Gleason score 8 or greater, it is 48%, demonstrating that while high Gleason scores are determinants of prostate cancer death, their positive predictive value is relatively low. 7

With each increase in Gleason score, tumor aggressiveness increases proportionally, making it one of the most important factors when selecting treatment 2, 6