Prognostic Impact of Biopsy Gleason 4 + 5, 5 + 4, and 5 + 5 in Grade Group 5 after Radical Prostatectomy

Grade Group 5 (GG5) subtypes exhibit prognostic heterogeneity, but evidence remains limited, and mainly derived from population-based studies. We evaluated their impact on oncologic outcomes following radical prostatectomy (RP).

We retrospectively analyzed 892 patients with biopsy-confirmed GG5 prostate cancer who underwent robot-assisted RP by a single surgeon between 2015 and 2024. Oncologic outcomes were compared among GG5 subtypes: Gleason score (GS) 4 + 5 (n = 688), 5 + 4 (n = 149), and 5 + 5 (n = 55). Primary endpoints were PSA persistence and biochemical recurrence (BCR). PSA persistence was assessed using multivariable logistic regression adjusting for potential confounders including age, race, PSA at diagnosis, clinical T stage, positive core rate, neoadjuvant hormonal therapy, and year of surgery. BCR was evaluated using Kaplan-Meier and log-rank analyses, followed by multivariable Cox regression with the same covariates.

Despite neoadjuvant hormonal therapy in 614 patients with comparable distribution across subtypes, organ-confined disease was observed in only 24% (211/892) following RP. PSA persistence occurred in 117 patients. During a median follow-up period of 36 months (Interquartile range: 18-60), BCR occurred in 242 patients, while 326 were followed up without PSA persistence or BCR for at least 60 months. Significant differences in BCR were observed among 3 subtypes (P = .028). Both GS 5 + 4 and 5 + 5 were independent predictors of PSA persistence (adjusted ORs: 1.80 [95% CI 1.08-3.01] and 2.33 [95% CI 1.08-5.02], respectively). GS 5 + 5 was significantly associated with BCR (adjusted HR 2.15 [95% CI 1.29-3.58]), whereas GS 5 + 4 was not (adjusted HR 1.30 [95% CI 0.94-1.81]). The main limitation was the relatively short follow-up.

Our study highlights the clinical relevance of GG5 subtyping within a cohort treated with a consistent surgical technique. Among these subtypes, GS 5 + 5 confers the highest risk of PSA persistence and BCR following RP. These findings support biopsy interpretation and preoperative counseling, particularly regarding multimodal treatment strategies for the highest-grade prostate cancer.