Gleason Score 3 + 4 (Grade Group 2) Prostate Cancer on Biopsy and Postoperative Pathological Upgrading: A Systematic Review and Meta-Analysis.

The clinical heterogeneity of needle biopsy (Bx)3 + 4 presents uncertainty to active surveillance as a treatment option for prostate cancer (PCa) patients. This meta-analysis demonstrates that 23.4% of Bx3 + 4 were upgraded at radical prostatectomy (RP). Age, cT, PI-RADS, greatest percentage of cancer involvement in biopsy (GPC) and number of positive cores are independent upgrading predictors, while Bx approaches showed no significant difference. Current guidelines recognize active surveillance as a treatment option for patients with intermediate-risk (IR)-PCa including selected cases with a diagnosis of Bx3 + 4. However, the upgrading of Bx3 + 4 in the RP is a critical but unaddressed concern. We investigated pathological RP upgrading from Bx3 + 4 and assessed its impact on oncological outcomes. A systematic literature search was performed up to February 2025 to identify the eligible studies discussing Bx3 + 4 on adverse RP pathology. Meta-analyses were performed on parameters with available information. Forty-eight studies comprising 63,119 patients with matched Bx3 + 4 and subsequent RP pathology were included. The median incidence of Bx3 + 4 upgraded to RP ≥ 4 + 3 and to RP ≥ 8 was 23.4% (IQR: 18.3%-23.7%) and 3.6% (IQR: 2.7%-4.9%), respectively. Age, cT, PI-RADS, GPC and No. positive cores were identified as independent and significant predictors for upgrading in Meta-analyses. No significant differences in upgrading were observed between systematic Bx (SBx) and MRI-targeted biopsy (TBx) methods or Transrectal (TR) and transperineal (TP) approaches. RP upgrading from Bx3 + 4 occurred in 23.4% cases, who may have a significantly worse biochemical recurrence survival. Different Bx methods did not make a significant impact on the rate of Bx3 + 4 to RP ≥ 4 + 3 upgrading.