A systematic review and meta-analysis of prognostic impact of different Gleason patterns in ISUP grade group 4

INTRODUCTION: This systematic review and meta-analysis was conducted to assess the prognostic differences between different Gleason patterns in patients with prostate cancer (PC) within Internal Society of Urological Pathology (ISUP) grade group 4 (GG 4). EVIDENCE ACQUISITION: PUBMED and Scopus databases were searched for articles published prior to December 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared overall survival (OS), cancer-specific survival (CSS), and surgical pathological outcomes in PC patients categorized as ISUP GG 4 (Gleason Score [GS] 4+4 vs. GS 3+5 or GS 5+3). Formal meta-analyses were performed for these outcomes. EVIDENCE SYNTHESIS: Ten studies with 42,041 patients were eligible for the systematic review and eight studies with 36,250 patients for meta-analysis. The treatment type of included study was three surgery and three radiotherapy. The other four studies included many kinds of treatments such as surgery, radiotherapy, androgen deprivation therapy, and chemotherapy. GS 4+4 was significantly associated with better OS (pooled hazard ratio (HR): 0.52, 95% confidential interval (CI): 0.29-0.91) than GS 3+5 or GS 5+3. Positive surgical margin rates were significantly lower with GS 4+4 than GS 3+5 and GS 5+3 (odds ratio [OR] 0.70/95% CI 0.64-0.77 and OR 0.70/95% CI 0.56-0.87, respectively). In contrast, different Gleason patterns in ISUP GG 4 were not significantly associated with CSS (pooled HR: 0.77, 95% CI: 0.56-1.06). CONCLUSIONS: GS 4+4 in patients with PC was associated with better OS and positive surgical margin rates. It seems likely that there is heterogeneity within ISUP GG 4. However, caution should be exercised in interpreting the conclusions drawn from this study, given the limitations of the study, which include the heterogeneity of the population of interest and the retrospective nature of the primary data evaluated.