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 Gleason score ranges from 6 to 10 and is calculated by adding the two most common cancer patterns observed on biopsy, with each pattern graded 1-5 by the pathologist. 1 Higher scores indicate more aggressive, poorly differentiated cancer cells that grow rapidly and carry worse prognosis. 1, 2
The modern Grade Group system simplifies interpretation: 2
- Grade Group 1 (Gleason ≤6): Well-formed individual glands only
- Grade Group 2 (Gleason 3+4=7): Predominantly well-formed glands
- Grade Group 3 (Gleason 4+3=7): Predominantly poorly-formed glands
- Grade Group 4 (Gleason 8): Only poorly-formed/fused glands
- Grade Group 5 (Gleason 9-10): No gland formation, often with necrosis
Risk Stratification Determines Treatment
The Gleason score combines with PSA level and clinical stage to assign risk categories that directly determine treatment options: 1, 2
Very Low Risk (Gleason ≤6, PSA <10, <3 cores positive)
- Life expectancy <20 years: Observation is appropriate 1
- Life expectancy ≥20 years: Definitive treatment recommended 1
- 5-year biochemical recurrence-free survival after surgery: 96% 2
Low Risk (Gleason ≤6, PSA <10)
- Life expectancy <10 years: Observation acceptable 1
- Life expectancy ≥10 years: Choose between active surveillance, radical prostatectomy, or radiation therapy 1
- 10-year prostate cancer-specific mortality on active surveillance: only 2.4% 2
Intermediate Risk (Gleason 7)
This is where the 3+4 versus 4+3 distinction becomes critical: 2, 3
- Favorable (Gleason 3+4=7): 5-year biochemical recurrence-free survival of 88% after surgery 2
- Unfavorable (Gleason 4+3=7): 5-year biochemical recurrence-free survival drops to 63% 2
- Life expectancy <10 years: Observation or treatment options 1
- Life expectancy ≥10 years: Definitive treatment with radical prostatectomy or radiation therapy, with or without 4-6 months of hormone therapy 1
The predominant pattern matters significantly—Gleason 4+3 behaves more aggressively than 3+4 despite both totaling 7. 3, 4
High Risk (Gleason 8-10)
These patients require aggressive treatment: 1, 3
- Life expectancy <5 years: Observation only 1
- Life expectancy ≥5 years: Radical prostatectomy with pelvic lymph node dissection OR radiation therapy with 2-3 years of androgen deprivation therapy 1, 3
- 5-year biochemical recurrence-free survival after surgery:
Critical Pitfalls to Avoid
Upgrading between biopsy and final pathology is extremely common. 5 Studies show that 65% of Gleason 6 on biopsy upgrades to Gleason 7a at prostatectomy, and 19% upgrades to Gleason 7b. 5 This means biopsy Gleason scores underestimate true disease severity in the majority of cases.
Extensive core involvement is an unfavorable risk factor. 3 A patient with 12 out of 18 positive cores, even with Gleason 3+4, should be considered for aggressive treatment rather than active surveillance due to high-volume disease. 3
Tertiary patterns matter. 2 Tumors with a tertiary Gleason grade 4 or 5 behave more aggressively than the sum of the two dominant patterns alone, even if not reflected in the final score. 2
Post-Treatment Monitoring
After radical prostatectomy, PSA should fall below detectable levels within 2 months. 3 Regular PSA monitoring is essential to detect 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
Gleason score 10 disease represents the most aggressive end of the spectrum (only 0.49% of cases), typically presents with either very low (<20 μg/L) or very high (>70 μg/L) PSA levels, and carries 5-year cancer-specific survival of only 66.7% despite aggressive treatment. 6