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

Gleason Score Significance in Prostate Cancer Treatment Planning

The Gleason score is the single most critical histopathologic factor that determines prostate cancer treatment strategy, directly dictating whether a patient receives active surveillance, definitive local therapy, or aggressive multimodal treatment based on risk stratification. 1, 2

How the Gleason Score Works

• The score ranges from 6 to 10, calculated by adding the two most common cancer patterns (each graded 1-5) identified by a pathologist examining prostate biopsy tissue under microscopy. 1
• Higher scores indicate more aggressive cancer cells that differ significantly from normal prostate tissue and grow more rapidly. 1
• The modern Grade Group system simplifies interpretation: Grade Group 1 (Gleason ≤6), Grade Group 2 (Gleason 3+4=7), Grade Group 3 (Gleason 4+3=7), Grade Group 4 (Gleason 8), and Grade Group 5 (Gleason 9-10). 2

Risk Stratification Based on Gleason Score

The Gleason score, combined with PSA level and clinical stage, categorizes patients into distinct risk groups with dramatically different prognoses and treatment pathways:

Very Low Risk (Gleason ≤6)

• Requires clinical stage T1c, PSA <10 ng/mL, <3 positive biopsy cores with ≤50% cancer involvement per core, and PSA density <0.15 ng/mL/g. 2
• These patients have 96% 5-year biochemical recurrence-free survival after radical prostatectomy. 2
• Treatment approach: Active surveillance is appropriate if life expectancy <20 years; definitive treatment if ≥20 years. 1

Low Risk (Gleason ≤6)

• Clinical stage T1-T2a with PSA <10 ng/mL. 2
• 10-year prostate cancer-specific mortality on active surveillance is only 2.4%. 2
• Treatment options: Active surveillance, radical prostatectomy, or radiation therapy. 1
• Observation is acceptable if life expectancy <10 years; observation or definitive treatment if ≥10 years. 1

Intermediate Risk (Gleason 7)

• Critical distinction: Gleason 3+4=7 (Grade Group 2) has significantly better prognosis than Gleason 4+3=7 (Grade Group 3) because the predominant pattern determines aggressiveness. 2, 3
• Favorable intermediate risk (Gleason 3+4, PSA <10 ng/mL): 88% 5-year biochemical recurrence-free survival. 2
• Unfavorable intermediate risk (Gleason 4+3 or Gleason 3+4 with PSA 10-20 ng/mL): 63% 5-year biochemical recurrence-free survival. 2
• Treatment approach: Observation or treatment if life expectancy <10 years; definitive treatment if ≥10 years. 1
• Definitive options: Radical prostatectomy or radiation therapy with or without brachytherapy, with or without 4-6 months of hormone therapy. 1

High Risk (Gleason 8-10)

• Defined by Gleason score 8-10, OR PSA >20 ng/mL, OR clinical stage T3-T4. 2
• Grade Group 4 (Gleason 8): 48% 5-year biochemical recurrence-free survival. 2
• Grade Group 5 (Gleason 9-10): 26% 5-year biochemical recurrence-free survival. 2
• Treatment approach: Observation only if life expectancy <5 years; aggressive definitive treatment if ≥5 years. 1
• Definitive options: Radical prostatectomy with pelvic lymph node dissection, OR radiation therapy with 2-3 years of androgen deprivation therapy, with or without brachytherapy. 1, 3

Critical Clinical Pitfalls

Biopsy Undergrading

• 65% of Gleason 6 biopsies upgrade to Gleason 7a at radical prostatectomy, and 19% upgrade to Gleason 7b. 4
• Extensive biopsy core involvement (e.g., 12/18 positive cores) is an unfavorable risk factor that shifts patients toward higher risk categories regardless of Gleason score. 3
• The pathology report must document the number of positive cores, percentage of involvement per core, maximum cancer length, and presence of tertiary high-grade patterns (Gleason 4 or 5), as these behave more aggressively than the primary score suggests. 2

Pattern Predominance Matters

• Gleason 4+3=7 behaves significantly worse than Gleason 3+4=7 due to the predominant pattern 4, which indicates poorer differentiation. 3, 5
• This distinction is essential for treatment planning and should always be specified in clinical decision-making. 2

Modern Gleason 6 Has Excellent Prognosis

• The modified Gleason grading system (post-2005) resulted in a more homogeneous Gleason score 6 category with uniformly excellent prognosis when organ-confined. 6
• This supports active surveillance as a safe option for appropriately selected low-risk patients. 6, 4

Treatment Algorithm Summary

Life expectancy and Gleason score together determine the treatment pathway:

• Gleason ≤6 + life expectancy <10 years → Observation 1
• Gleason ≤6 + life expectancy ≥10 years → Active surveillance or definitive treatment 1
• Gleason 7 + life expectancy <10 years → Observation or treatment 1
• Gleason 7 + life expectancy ≥10 years → Definitive treatment (surgery or radiation ± short-term hormones) 1
• Gleason 8-10 + life expectancy <5 years → Observation 1
• Gleason 8-10 + life expectancy ≥5 years → Aggressive definitive treatment (surgery with lymph node dissection OR radiation with 2-3 years hormones) 1, 3

Post-Treatment Considerations

• After radical prostatectomy, PSA should fall below detection within 2 months, and regular PSA monitoring detects biochemical recurrence early. 3
• Adverse pathological features (positive margins, seminal vesicle invasion, extracapsular extension) warrant consideration of adjuvant radiation therapy or androgen deprivation therapy. 3
• Genomic testing (e.g., Decipher score) may refine post-surgical adjuvant therapy decisions, though high-volume disease and Gleason 4+3 pattern mandate definitive treatment regardless of genomic risk. 3