What is the significance of the Gleason score in determining the treatment plan for prostate cancer?

The Significance of Gleason Score in Prostate Cancer Treatment Planning

The Gleason score is a critical determinant in prostate cancer treatment planning, directly correlating with cancer aggressiveness and serving as a key factor in risk stratification that guides specific treatment recommendations based on cancer severity. 1

Understanding the Gleason Score

• The Gleason score is determined by a pathologist examining prostate biopsy tissue under a microscope, evaluating how much cancer cells differ from normal prostate cells, with scores ranging from 6 to 10 1
• The score is calculated by adding the grades of the two most common cancer patterns in the biopsy, with each pattern scored from 1 to 5, and higher scores indicating more aggressive cancer 1
• The primary (most predominant) pattern is listed first, followed by the secondary pattern, which has significant prognostic implications (e.g., Gleason 4+3 has worse prognosis than 3+4 despite both summing to 7) 2

Gleason Score Ranges and Their Significance

• Gleason score 6 (3+3): Well-differentiated cancer cells that look similar to normal cells and tend to grow slowly 1
• Gleason score 7: Moderately differentiated cancer cells with intermediate aggressiveness 1
  • Gleason 3+4 has better prognosis than 4+3, despite both having a total score of 7 3
• Gleason scores 8-10: Poorly differentiated cancer cells that look very different from normal cells and tend to grow more rapidly 1
• Recent research suggests that there is prognostic heterogeneity even within high Gleason scores (8-10), with differences in outcomes between scores like 3+5,4+4,5+3 and between 4+5+4,5+5 4

Role in Treatment Decision-Making

• The Gleason score, along with PSA level and clinical stage, determines the risk category (very low, low, intermediate, or high risk), which directly guides treatment recommendations 5, 1
• According to the National Comprehensive Cancer Network algorithm:
  • Very low risk (Gleason ≤6, <3 cores positive, PSA <10 ng/mL): Observation if life expectancy <20 years; observation or definitive treatment if ≥20 years 5
  • Low risk (Gleason ≤6): Observation if life expectancy <10 years; observation or definitive treatment if ≥10 years 5
  • Intermediate risk (Gleason 7): Observation or treatment options if life expectancy <10 years; definitive treatment recommended if ≥10 years 5
  • High risk (Gleason 8-10): Observation only if life expectancy <5 years; radical prostatectomy or radiation therapy (with or without hormone therapy for 2-3 years) if ≥5 years 5, 2

Treatment Options Based on Gleason Score

• For Gleason 6 (low risk): Active surveillance, radical prostatectomy, or radiation therapy options 5, 1
• For Gleason 7 (intermediate risk): Radical prostatectomy or radiation therapy (with or without brachytherapy; with or without hormone therapy for 4-6 months) 5
• For Gleason 8-10 (high risk): Radical prostatectomy or radiation therapy (with or without brachytherapy; with or without hormone therapy for 2-3 years) 5, 2

Clinical Implications and Challenges

• The Gleason score is one of the most reliable prognostic predictors in prostate cancer, directly related to tumor size, margin status, and pathologic stage 6
• Despite its importance, studies show that patient understanding of the Gleason scoring system is often low, which can impact shared decision-making 7
• The combination of Gleason grading with nuclear/nucleolar subgrading (Helpap score) may improve grading concordance between biopsy and radical prostatectomy specimens 8
• Recent research questions the clinical value of grouping Gleason scores into simplified grade groups, as this may obscure important prognostic differences between specific Gleason scores 4

Pitfalls and Considerations

• Biopsy Gleason scores may underestimate the true grade found at radical prostatectomy, with studies showing upgrading from Gleason 6 to Gleason 7a and 7b in 65% and 19% of cases, respectively 8
• The prognostic value of the Gleason score may diminish with time since diagnosis, with knowledge about its significance decreasing among patients as years since biopsy increase 7
• When evaluating Gleason 7 cancers, it's crucial to distinguish between 3+4 and 4+3 patterns, as they have significantly different prognoses despite the same total score 2, 3