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.