Prognostic Differences in ISUP Grade Group 4: a Systematic Review and Meta-Analysis

Area of Science:

• Uropathology
• Oncology
• Prognostic Biomarkers

Background:

• The International Society of Urologic Pathology (ISUP) established a five-tiered grading system for prostate cancer prognostication.
• Emerging evidence suggests potential heterogeneity within ISUP grade group 4, impacting patient outcomes.

Purpose of the Study:

• To systematically review and meta-analyze existing literature to determine if prognostic differences exist within ISUP grade group 4.
• To evaluate outcome variations based on specific Gleason score combinations within ISUP grade group 4.

Main Methods:

• A systematic literature search was performed to identify studies investigating ISUP grade group 4 heterogeneity.
• Meta-analysis was conducted on four studies reporting all-cause mortality (ACM) and prostate cancer-specific mortality (PCSM).

Main Results:

• The 5+3/3+5 Gleason score combination demonstrated a statistically significant higher ACM compared to the 4+4 group (HR 1.23, 95% CI 1.08-1.41).
• No significant difference in PCSM was observed between the 5+3/3+5 and 4+4 groups (HR 1.34, 95% CI 0.89-2.01), though heterogeneity was high.
• Evidence suggests heterogeneity within ISUP grade group 4, but findings remain inconclusive due to methodological variations.

Conclusions:

• Prostate cancer patients with Gleason scores 5+3/3+5 within ISUP grade group 4 exhibit higher all-cause mortality than those with 4+4.
• Further research with standardized methodologies is essential to definitively clarify prognostic differences within ISUP grade group 4.