How does the Gleason score (Prostate-Specific Antigen score) influence the treatment plan for prostate cancer?

The Influence of Gleason Score on Prostate Cancer Treatment Planning

The Gleason score is a critical determinant in risk stratification for prostate cancer that directly guides treatment decisions based on tumor aggressiveness, with higher scores (8-10) indicating more aggressive disease requiring more intensive treatment approaches. 1

Understanding the Gleason Score

The Gleason score represents the sum of the two most predominant histological patterns observed in prostate cancer tissue, with each pattern graded from 1 to 5 based on the degree of architectural differentiation:

• Calculation: Sum of two most common patterns (range: 2-10)
• Interpretation:
  • Score ≤6: Well-differentiated histology, lower risk
  • Score 7: Intermediate differentiation
  • Score 8-10: Poorly differentiated histology, worst prognosis (high risk) 1

Important distinction: The order of Gleason patterns matters - a 4+3=7 score carries a worse prognosis than a 3+4=7 score 1

Risk Classification Based on Gleason Score

The Gleason score forms a cornerstone of risk classification systems that guide treatment decisions:

• Low-risk: Gleason score ≤6, PSA <10 ng/mL, clinical stage T1-T2a
• Intermediate-risk: Gleason score 7, PSA 10-20 ng/mL, clinical stage T2b
• High-risk: Gleason score 8-10, PSA >20 ng/mL, clinical stage T2c or higher 1

Treatment Algorithm Based on Risk Stratification

For Low-Risk Disease (Gleason ≤6):

• Patients with life expectancy <10 years: Active surveillance
• Patients with life expectancy ≥10 years:
  • Active surveillance
  • Radical prostatectomy
  • External beam radiation therapy
  • Brachytherapy 1

For Intermediate-Risk Disease (Gleason 7):

• Patients with 3+4=7:
  • Radical prostatectomy
  • External beam radiation therapy ± brachytherapy
  • Short-term (4-6 months) androgen deprivation therapy may be added to radiation
• Patients with 4+3=7: More aggressive approach warranted
  • Radical prostatectomy with extended pelvic lymph node dissection
  • External beam radiation therapy + brachytherapy boost
  • Consider longer-term (12-18 months) androgen deprivation therapy with radiation 1, 2

For High-Risk Disease (Gleason 8-10):

• Primary treatment:
  • Radical prostatectomy with extended pelvic lymph node dissection
  • External beam radiation therapy + long-term (2-3 years) androgen deprivation therapy 1, 3

Important Clinical Considerations

1. Prognostic Significance: Gleason score is the strongest prognostic factor for prostate cancer-specific survival, even in metastatic disease 3

2. Tertiary Patterns: Tumors with tertiary Gleason grade 4 or 5 behave more aggressively than their primary score would suggest 1

3. Organ-Confined High-Grade Disease: Even when high-grade tumor (Gleason 8-10) is organ-confined, it is associated with a relatively unfavorable short-term outcome 4

4. Gleason 7 Heterogeneity: A total Gleason score of 7 represents the most common grade and most challenging with respect to prognosis, with significant differences between 3+4 and 4+3 patterns 5, 2

5. Post-Treatment Assessment: Gleason grading should not be performed in patients who have received radiotherapy or hormonal therapy 6

Pitfalls to Avoid

• Underestimating Gleason 7: Don't group Gleason 7 with lower-grade disease; these patients may benefit from more aggressive treatment strategies 2

• Overlooking Pattern Distribution: The distribution between primary and secondary patterns significantly impacts prognosis, especially for Gleason 7 and 9 tumors 1, 5

• Neglecting Tertiary Patterns: High-grade tertiary patterns should be reported as they impact prognosis 1

• Relying Solely on Total Score: The specific pattern combination (e.g., 4+3 vs. 3+4) provides more prognostic information than the total score alone 1

The Gleason score remains an essential tool for treatment planning in prostate cancer, providing crucial information about tumor aggressiveness that directly informs therapeutic decision-making and helps predict patient outcomes.