INTRODUCTION: There are questions regarding whether grade group (GG) 4 prostate cancer (PC) is heterogeneous in terms of prognosis. We assessed prognostic differences in PC patients within GG 4 treated with radical prostatectomy (RP). MATERIAL AND METHODS: Biochemical recurrence (BCR)-free, cancer-specific, and overall survival were analyzed in 787 PC patients with GG 4 based on RP pathology (Gleason score (GS) 3 + 5: 189, GS 4 + 4: 500, and GS 5 + 3: 98). Logistic regression analysis was performed to assess factors predictive of high-risk surgical pathological features. Cox regression models were used to evaluate potential prognostic factors of survival. RESULTS: Within a median follow-up of 86 months, 378 patients (48.0%) experienced BCR and 96 patients (12.2%) died, 42 of whom (5.3%) died of PC. GS 5 + 3 was significantly associated with worse BCR-free and cancer-specific survival, as well as higher positive surgical margin, lymph node metastasis, extraprostatic extension, and non-organ-confined disease rates, than GS 3 + 5 and higher positive surgical margin, lymph node metastasis, extraprostatic extension, and non-organ-confined disease rates than GS 4 + 4 (P < 0.05). GS 4 + 4 was significantly associated with worse BCR-free survival and higher extraprostatic extension, and non-organ-confined disease rates than GS 3 + 5 (P < 0.05). Inclusion of the different Gleason patterns improved the discrimination of a model for prediction of all survival outcomes compared to standard prognosticators. CONCLUSIONS: There is considerable heterogeneity within GG 4 in terms of oncological and surgical pathological outcomes. Primary and secondary Gleason patterns should be considered to stratify high-risk PC patients after RP.

Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal Canada

Department of Pathology Hôpital Tenon Sorbonne University Paris France

Department of Urology Mayo Clinic Rochester MN USA

Department of Urology Mayo Clinic Rochester MN USA; VA Health Services Research and Development Fellowship Department of Urology University of California Los Angeles USA

Department of Urology Medical University of Vienna Vienna Austria; Department of Urology Shariati Hospital Tehran University of Medical Sciences Tehran Iran

Department of Urology Medical University of Vienna Vienna Austria; Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology Medical University of Vienna Vienna Austria; Department of Urology University Hospital of Tours Tours France

Department of Urology Medical University of Vienna Vienna Austria; Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology Medical University of Vienna Vienna Austria; Departments of Pathology The Jikei University School of Medicine Tokyo Japan; Division of Urology Department of Special Surgery The University of Jordan Amman Jordan; Department of Urology Weill Cornell Medical College New York NY USA; Department of Urology University of Texas Southwestern Dallas TX USA; Karl Landsteiner Institute of Urology and Andrology Vienna Austria; Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic; European Association of Urology Research Foundation Arnhem Netherlands

Department of Urology Medical University of Vienna Vienna Austria; Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Department of Urology The Jikei University School of Medicine Tokyo Japan

Departments of Pathology The Jikei University School of Medicine Tokyo Japan

Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany; Department of Urology University Hospital Hamburg Eppendorf Hamburg Germany

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