What is the significance of the Gleason score in assessing the risk of prostate cancer?

Gleason Score and Prostate Cancer Risk Assessment

The Gleason score is the most critical histopathologic predictor of prostate cancer aggressiveness, determined by adding the two most dominant cancer patterns (each graded 1-5) to create a score ranging from 6-10, with higher scores indicating more aggressive disease and worse prognosis. 1

How the Gleason Score is Determined

• The pathologist identifies the most dominant Gleason pattern and the pattern with the highest grade to calculate the Gleason score. 1
• Each pattern is graded from 1 to 5 based on how much the cancer cells differ from normal prostate tissue, with 1 being most similar to normal and 5 being most abnormal. 2
• The two most common patterns are added together (e.g., 3+4=7), though tumors with a tertiary Gleason grade 4 or 5 behave more aggressively than the sum of the two dominant patterns alone. 1
• Gleason grades 1 and 2 should not be reported on biopsies. 1

Modern Grade Group Classification (ISUP 2014)

The International Society of Urological Pathology introduced a simplified Grade Group system that correlates with Gleason scores: 1

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

Risk Stratification Based on Gleason Score

Very Low Risk

• All of: Clinical stage T1c, Gleason score ≤6 (Grade Group 1), PSA <10 ng/mL, <3 biopsy cores positive, ≤50% cancer in each core, PSA density <0.15 ng/mL/g 1, 2
• 5-year biochemical recurrence-free survival after radical prostatectomy: 96% 1, 3
• Active surveillance is the primary recommended management strategy 3

Low Risk

• All of: Clinical stage T1-T2a, Gleason score ≤6 (Grade Group 1), PSA <10 ng/mL 1
• 10-year prostate cancer-specific mortality on active surveillance: only 2.4% 3
• 90% probability of biochemical control at 5 years with treatment 1

Intermediate Risk (Favorable)

• Gleason score 3+4=7 (Grade Group 2) with PSA <10 ng/mL 1
• 60% probability of biochemical control at 5 years 1
• 5-year biochemical recurrence-free survival after radical prostatectomy: 88% 1

Intermediate Risk (Unfavorable)

• Gleason score 3+4=7 (Grade Group 2) with PSA 10-20 ng/mL, OR Gleason score 4+3=7 (Grade Group 3) with PSA <20 ng/mL 1
• Gleason 4+3 has significantly worse prognosis than 3+4 due to the predominant pattern 4 4
• 5-year biochemical recurrence-free survival after radical prostatectomy for Grade Group 3: 63% 1

High Risk

• Any of: Clinical stage T3-T4, OR Gleason score 8-10 (Grade Groups 4-5), OR PSA >20 ng/mL 1
• 30% probability of biochemical control at 5 years 1
• 5-year biochemical recurrence-free survival after radical prostatectomy for Grade Group 4: 48%; Grade Group 5: 26% 1

Critical Prognostic Nuances Within High-Grade Disease

Recent population-based data demonstrates significant prognostic heterogeneity even within Grade Groups 4 and 5 that is lost when collapsing Gleason scores into groups: 5, 6

• Gleason score 5+3 (Grade Group 4) and 4+5 (Grade Group 5) have nearly identical outcomes, with 10-year prostate cancer-specific mortality of 0.44 and 0.45 respectively 5
• Within Gleason 9-10 disease, 10-year prostate cancer-specific mortality varies substantially: 0.45 for Gleason 4+5,0.56 for Gleason 5+4, and 0.66 for Gleason 5+5 6
• Gleason score 10 confers significantly shorter time to biochemical recurrence compared to Gleason 8-9 (AHR 2.67, p=0.018) 7

Essential Biopsy Reporting Requirements

The pathology report must include: 1

• The maximum length of cancer involvement in each core 1
• The most common (primary) and worst (secondary) Gleason grades 1
• The extent of tumor involvement in each biopsy core 1
• Number of positive cores and percentage of involvement 1

These parameters help predict pathological stage, tumor volume, risk of positive margins, and progression-free survival. 1

Common Pitfalls in Gleason Scoring

• Upgrading from biopsy to radical prostatectomy occurs frequently: 65% of Gleason 6 cases upgrade to 7a and 19% to 7b at surgery 8
• Sampling error is inherent in prostate biopsies, requiring minimum 8-12 cores with sampling from both peripheral and anterolateral zones 1
• The positive predictive value of high Gleason scores for prostate cancer death is relatively modest: only 29% for Gleason ≥7 and 48% for Gleason ≥8 die from prostate cancer 9
• Collapsing Gleason scores into Grade Groups results in loss of prognostic information, particularly for high-grade cancers 5, 6