Patients with an initial biopsy-confirmed Gleason score (GS) 3+3 prostate cancer (PCa) (Grade Group 1) are typically categorized as having low-risk disease. However, a subset may experience Gleason score progression upon final pathology after radical prostatectomy (RP), which can alter prognosis and treatment strategies. This study aims to identify predictors of Gleason score progression from an initial GS of 3+3 and to evaluate the associated clinical outcomes, including biochemical recurrence.

A retrospective cohort of men with biopsy-confirmed GS 3+3 PCa who underwent RP was analyzed. The study was approved by the Institutional Review Board at Kaohsiung Medical University Hospital. Only patients with both initial biopsy and final pathology data were included, while those without complete follow-up data were excluded. Data collected from electronic health records included patient demographics, clinical variables such as Prostate-Specific Antigen (PSA) levels, PSA density, and prostate volume (PV), as well as final pathology findings. Multiparametric MRI (mpMRI) data were incorporated when available. The primary outcome was Gleason score progression, defined as an upgrade to 3+4, 4+3, or higher on final pathology. Secondary outcomes included biochemical recurrence (PSA ≥ 0.2 ng/mL) and overall survival.

A total of 121 men met inclusion criteria. Gleason score progression occurred in 78 (64.5%) patients following RP. Patients with GS upgrading had significantly higher PSA density and smaller PV compared to those who remained at GS 3+3. Multivariate analysis identified older age (p=0.0147), smaller PV (p=0.0049), and perineural invasion (PNI) (p=0.0155) as independent predictors of GS progression. Biochemical recurrence occurred in 35 patients (28.9%), and these patients had significantly elevated pre-biopsy PSA levels and higher PSA density compared to non-recurrent patients. PNI was also more frequent in patients with biochemical recurrence.

Gleason score upgrading and biochemical recurrence are significant considerations in patients initially diagnosed with GS 3+3 prostate cancer. Older age, smaller prostate volume, and PNI were strong predictors of Gleason score upgrading, while elevated pre-biopsy PSA levels were associated with increased risk of biochemical recurrence. These findings emphasize the need for enhanced risk stratification in low-risk PCa patients to guide management decisions.