ISUP Grade for Prostate Cancer
The ISUP (International Society of Urological Pathology) grade is a 5-tier grading system (Grade Groups 1-5) that replaced the traditional Gleason score reporting and provides superior prognostic stratification for prostate cancer patients.
The ISUP Grading System
The ISUP grade groups directly correspond to Gleason scores as follows 1:
- ISUP Grade Group 1: Gleason score ≤6 (3+3)
- ISUP Grade Group 2: Gleason score 7 (3+4)
- ISUP Grade Group 3: Gleason score 7 (4+3)
- ISUP Grade Group 4: Gleason score 8 (4+4,3+5+3)
- ISUP Grade Group 5: Gleason score 9-10 (4+5+4,5+5)
Key Clinical Implementation Points
Both the traditional Gleason score AND the ISUP grade group should be reported on pathology reports 1. The ISUP system was specifically designed to improve patient communication while maintaining prognostic accuracy.
Critical Reporting Requirements
Each biopsy site must include 2:
- Location
- Gleason score
- ISUP grade group
- Extent of disease
- Presence of lymphovascular invasion (if identified)
- Extraprostatic extension (if present)
- Intraductal carcinoma and invasive cribriform pattern (independent factors for metastasis and cancer-specific survival)
Prognostic Significance
The ISUP grading system demonstrates clear prognostic stratification for cancer-specific survival and biochemical recurrence 3:
8-year outcomes in radiotherapy-treated patients:
- Grade Group 1: 90% BCF-free, 98% DM-free
- Grade Group 2: 82% BCF-free, 96% DM-free
- Grade Group 3: 74% BCF-free, 92% DM-free
- Grade Group 4: 71% BCF-free, 88% DM-free
- Grade Group 5: 58% BCF-free, 83% DM-free
In organ-confined disease after radical prostatectomy, 7-year cancer-specific survival rates are 99.6% for Grade Groups 1-3,98.2% for Grade Group 4, and 93.8% for Grade Group 5 4.
Important Clinical Caveats
MRI-Targeted Biopsy Grade Shift
MRI-targeted biopsies detect higher-grade cancer more sensitively than systematic biopsies, meaning ISUP Grade Group 2 cancers detected by MRI-targeted biopsy have better prognosis on average than those detected by systematic biopsy alone 2. Interpret MRI-targeted biopsy results with this grade shift in mind.
Active Surveillance Exclusions
Patients with cribriform or intraductal histology must be excluded from active surveillance 2. ISUP Grade Group 3 disease should also be excluded from active surveillance protocols 2.
Percentage Pattern 4 Reporting
For ISUP Grade Group 2 tumors with minimal pattern 4 (<10%), reporting the percentage of pattern 4 helps determine active surveillance eligibility 2.
Central Pathology Review
There is poor agreement (κ = 0.19) between local and central pathology-derived grade groups 3, emphasizing the importance of expert pathology review in clinical trials and complex cases.
Treatment Implications by Grade Group
The current EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines stratify treatment based on ISUP grade groups 2:
- Grade Group 1: Active surveillance is strongly recommended for patients with life expectancy >10 years
- Grade Group 2: Selected patients with favorable features may be offered active surveillance (weak recommendation)
- Grade Group 3: Requires metastatic screening with at least cross-sectional imaging and bone scan; PSMA PET/CT if available
- Grade Groups 4-5: Mandatory metastatic screening with PSMA PET/CT if available