Risk Stratification of Prostate Cancer into Favorable and Unfavorable Categories
Prostate cancer is categorized into favorable and unfavorable intermediate-risk groups based on three key factors: primary Gleason pattern, percentage of positive biopsy cores, and number of NCCN intermediate-risk factors present. 1
Defining Favorable Intermediate-Risk Disease
Favorable intermediate-risk prostate cancer is defined as having ALL of the following criteria: 1, 2
- Predominant Gleason grade 3 (Gleason score 3+4=7, or Grade Group 2)
- <50% positive biopsy cores
- ≤1 NCCN intermediate-risk factor (T2b-c, PSA 10-20 ng/mL, or Gleason score 7)
Alternatively, the AUA/ASTRO guideline defines favorable intermediate-risk as Grade Group 1 with PSA 10-<20 ng/mL or clinical stage T2b-c with <50% biopsy cores positive, OR Grade Group 2 with PSA <10 ng/mL and clinical stage T1-2a with <50% biopsy cores positive. 3
Defining Unfavorable Intermediate-Risk Disease
Unfavorable intermediate-risk prostate cancer is defined by having ANY of the following: 1, 2
- Primary Gleason pattern 4 (Gleason score 4+3=7, or Grade Group 3)
- ≥50% positive biopsy cores
- >1 NCCN intermediate-risk factor present simultaneously
The AUA/ASTRO guideline specifies unfavorable intermediate-risk as Grade Group 1 with PSA 10-<20 ng/mL AND clinical stage T2b-c, OR Grade Group 2 with PSA 10-<20 ng/mL and/or clinical stage T2b-c and/or ≥50% biopsy cores positive, OR Grade Group 3 with PSA <20 ng/mL. 3
Clinical Significance of This Distinction
The unfavorable intermediate-risk group demonstrates significantly worse outcomes compared to favorable intermediate-risk patients: 1, 2
- PSA recurrence-free survival is markedly inferior in unfavorable intermediate-risk disease 1, 2
- Distant metastasis rates are significantly higher (5.4% vs 1.6% at 5 years) 1
- Prostate cancer-specific mortality is increased in the unfavorable group 1, 2
Validation studies confirm that unfavorable intermediate-risk patients have 2.87 times higher biochemical failure rates and 3.14 times higher distant metastasis rates compared to favorable intermediate-risk patients. 4
Important Calculation Detail for Biopsy Core Percentage
When calculating the percentage of positive biopsy cores with MRI-targeted biopsies, multiple cores from the same targeted lesion should be counted as a single core. 3 This prevents artificial inflation of the positive core percentage when multiple samples are obtained from one lesion. The calculation is: (total number of cores containing cancer ÷ total number of cores obtained) × 100. 2
Treatment Implications
Favorable intermediate-risk patients may be considered for active surveillance with close monitoring, though this should be approached with caution and requires informed decision-making. 1 These patients have outcomes similar to low-risk disease. 5
Unfavorable intermediate-risk patients should not be offered active surveillance and require definitive treatment, as their outcomes are similar to standard high-risk disease. 5, 6 They may require treatment intensification such as longer-duration androgen deprivation therapy with radiation. 1
Common Pitfall to Avoid
Do not rely solely on Gleason score 3+4 versus 4+3 without considering the other risk factors. 1, 2 A patient with Gleason 3+4 disease can still be classified as unfavorable intermediate-risk if they have ≥50% positive cores or multiple intermediate-risk factors present. 1