Progression Risk of Gleason Score 6 Prostate Cancer
Gleason score 6 prostate cancer has an extremely low chance of becoming more aggressive, with prostate cancer-specific mortality of only 2.4% at 10 years and 5-year biochemical recurrence-free survival of 96% after treatment. 1, 2
Understanding Gleason 6 Biology
Gleason score 6 (ISUP Grade Group 1) prostate cancer is now recognized as having minimal aggressive potential:
The 5-year biochemical recurrence-free progression probability after radical prostatectomy for Grade Group 1 is 96% (95% CI, 95-96%), demonstrating that true Gleason 6 disease rarely progresses. 2
Over 97% of men with low-risk prostate cancer (which includes Gleason 6) are likely to die of something other than prostate cancer, emphasizing the indolent nature of this disease. 3
Prostate cancer-specific mortality is only 2.4% at 10 years for low-risk patients on active surveillance, confirming the minimal threat to life expectancy. 1
The Critical Issue: Upgrading vs. True Progression
The main concern with Gleason 6 is not that it becomes more aggressive, but rather that the initial biopsy may have undersampled higher-grade disease that was already present:
Gleason score upgrading occurs in 43% to 61% of biopsy Gleason 6 patients at prostatectomy, depending on PSA level (43% for PSA <10 ng/mL, increasing to 61% for PSA 20-29.9 ng/mL). 4
This represents sampling error rather than biological progression—the higher-grade cancer was already there but missed on initial biopsy. 4
Among active surveillance patients with no tumor found on first rebiopsy, only 5% subsequently required treatment, suggesting that when Gleason 6 is accurately diagnosed, progression is rare. 3
Active Surveillance Outcomes Support Low Progression Risk
The excellent outcomes from active surveillance protocols demonstrate the stability of true Gleason 6 disease:
In carefully selected patients (Gleason ≤6, PSA ≤10, ≤2 cores positive with ≤20% tumor), 86% remained on active surveillance for a mean follow-up of 44 months. 3
Of the 14% who were treated, 50% had no tumor on first rebiopsy, suggesting many interventions were triggered by anxiety or protocol requirements rather than true progression. 3
No patient in the active surveillance cohort progressed after treatment, indicating that monitoring successfully identifies any concerning changes before they become life-threatening. 3
Risk Stratification Context
Current guidelines classify Gleason 6 as low-risk disease, with specific criteria for "very low-risk" that further reduces progression concerns:
Very low-risk criteria include: T1c stage, Gleason score 6, PSA <10 ng/mL, <3 biopsy cores positive, ≤50% cancer in each core, and PSA density <0.15 ng/mL/g. 2, 1
Patients meeting very low-risk criteria with life expectancy >20 years are recommended for active surveillance as the primary management strategy. 2
Treatment of low-risk prostate cancer enhances quality-adjusted survival by only 1.2 months while causing significant urinary, sexual, and bowel dysfunction. 1
Important Caveats
Higher PSA levels within the Gleason 6 category increase the risk of finding higher-grade disease on repeat biopsy or at surgery, though this reflects sampling error rather than progression. 4
Confirmatory biopsy within 6-12 months of diagnosis is essential to ensure accurate grading and rule out undersampling of higher-grade disease. 1
The presence of cribriform or intraductal carcinoma patterns significantly worsens prognosis, but these patterns by definition would upgrade the cancer beyond Gleason 6. 5