Prognostic differences among Grade Group 4 subgroups in robotic‐assisted radical prostatectomy

OBJECTIVES: To investigate whether the International Society of Urological Pathology Grade Group 4 (GG 4) subgroups have different oncological outcomes in Japanese prostate cancer (PCa) patients undergoing robotic‐assisted radical prostatectomy (RARP). PATIENTS AND METHODS: We conducted a retrospective multicentre cohort study in PCa patients undergoing RARP at 10 institutions in Japan. Pre‐ and post‐operative variables were collected from enrolled patients. We evaluated biochemical recurrence and clinical and pathological variables in the different GG 4 subgroups. RESULTS: A total of 3195 patients were enrolled in the study. Among them, 298 patients with GG 4 tumours (pathological Gleason scores [GSs] of 3 + 5 [N = 37], 4 + 4 [N = 257] and 5 + 3 [N = 4]) based on RARP specimens were analysed. The median follow‐up period was 25.2 months. The 3‐year biochemical recurrence (BCR)‐free survival (BCRFS) rate in the overall population was 74.5%. The 3‐year BCRFS rates in the pathological GS 3 + 5, GS 4 + 4 and GS 5 + 3 subgroups were 93.8%, 71.9% and 50.0%, respectively (P = 0.01). In multivariate analysis, pathological GS based on RARP specimens, PSA levels at surgery, pathological T stage, pathological N stage and surgical margins were independent risk factors significantly associated with BCRFS. In particular, patients with pathological GSs 4 + 4 and 5 + 3 were at higher risk of BCR than patients with pathological GS 3 + 5 (hazard ratio 4.54, P = 0.03 and hazard ratio 11.2, P = 0.01, respectively). The study limitations include the lack of central pathological specimen evaluation. CONCLUSIONS: For patients with localized PCa undergoing RARP, pathological GS 4 + 4 and GS 5 + 3 were significantly associated with worse BCRFS than pathological GS 3 + 5. Pathological GS 3 + 5 may be overrated in GG 4. This observation emphasizes that primary and secondary GS should be considered to accurately stratify the risk of BCR after RARP.