Primary Gleason grade and Gleason grade group at positive surgical margins: a systematic review and meta-analysis

Objectives: To systematically review and perform a meta-analysis of studies investigating the role of primary Gleason grade (PGG), Gleason score (GS) or Gleason grade group (GGG) at positive surgical margins (PSMs) after radical prostatectomy (RP) in predicting biochemical recurrence (BCR) and oncological outcomes. Methods: A systematic search was conducted using the MEDLINE, Scopus, Embase and Cochrane databases according to Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Studies published between 2005 and 2019 were included. The quality of the studies selected was assessed, and a protocol was registered and published in advance (PROSPERO: CRD42019131800). The primary outcome measure was BCR. Secondary outcome measures included cancer-specific survival, metastasis-free survival and overall mortality during the follow-up period. Results: Our systematic search yielded 3116 unique results. Ten studies were selected for meta-analysis. The sample sizes of PSM cohorts varied from 200 to 956, while the median follow-up ranged from 1.5 to 13 years. Most studies used BCR as a surrogate marker for disease progression; only two studies reported other oncological outcomes. Meta-analysis was performed in selected groups (PGG, GS and GGG). PGG 4 or 5 at the PSM was found to be predictive of BCR (hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.37–2.02; P < 0.01). GGG > 1 at margin was also predictive of BCR compared to GGG 1 (GGG 1 vs 2: HR 2.35, 95% CI 1.6 −3.46; P < 0.001; GGG 1 vs 3: HR 3.95, 95% CI 1.82–8.57; P = 0.005; GGG 1 vs 4: HR 7.17, 95% CI 1.76–29.17; P = 0.006; and GGG 1 vs 5: HR 12.37, 95% CI 1.80–84.82; P = 0.01). Conclusion: Gleason score, PGG and GGG at the PSM are associated with a significantly increased risk of BCR. Longer-term studies are needed to investigate the utility of PGG, GS or GGG at the PSM in their ability to predict not only BCR but other outcomes such as cancer-specific survival, metastasis-free survival and overall survival.