BACKGROUND: Grade group (GG) 4 prostate cancer (PC) is considered a single entity; however, there are questions regarding prognostic heterogeneity. This study assessed the prognostic differences among various Gleason scores (GSs) classified as GG 4 PC on biopsy before radical prostatectomy (RP). METHODS: We conducted a multicenter retrospective study, and a total of 1791 patients (GS 3 + 5: 190; GS 4 + 4: 1557; and GS 5 + 3: 44) with biopsy GG 4 were included for analysis. Biochemical recurrence (BCR)-free survival, cancer-specific survival, and overall survival were analyzed using the Kaplan-Meier method and the log-rank test. Logistic regression analysis was performed to identify factors associated with high-risk surgical pathologic features. Cox regression models were used to analyze time-dependent oncologic endpoints. RESULTS: Over a median follow-up of 75 months, 750 patients (41.9%) experienced BCR, 146 (8.2%) died of any causes, and 57 (3.2%) died of PC. Biopsy GS 5 + 3 was associated with significantly higher rates of GS upgrading in RP specimens than GS 3 + 5 and GS 4 + 4. On multivariable analysis adjusted for clinicopathologic features, different GSs within GG 4 were significantly associated with BCR (p = 0.03) but not PC-specific or all-cause mortality. Study limitations include the lack of central pathological specimen evaluation. CONCLUSIONS: Patients with GG 4 at biopsy exhibited some limited biological and clinical heterogeneity. Specifically, GS 5 + 3 had an increased risk of GS upgrading. This can help individualize patients' counseling and encourage further study to refine biopsy specimen-based GG classification.

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

Department of Pathology Hôpital Tenon Sorbonne University Paris France

Department of Pathology The Jikei University School of Medicine Tokyo Japan

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology King Fahad Specialist Hospital Dammam Saudi Arabia

Department of Urology Mayo Clinic Rochester MN 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 The Jikei University School of Medicine Tokyo Japan

Department of Urology University Hospital Hamburg Eppendorf Hamburg Germany

Department of Urology University Hospital of Tours Tours France

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology VA Health Services Research and Development Fellowship University of California Los Angeles CA USA

Department of Urology Weill Cornell Medical College New York NY USA

Division of Urology Department of Special Surgery The University of Jordan Amman Jordan

European Association of Urology Research Foundation Arnhem The Netherlands

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany

Men's Health and Reproductive Health Research Center Shahid Beheshti University of Medical Sciences Tehran Iran

Research Center for Evidence Based Medicine Tabriz University of Medical Sciences Tabriz Iran

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ASO Author Reflections: Is There Any Difference Among Various Gleason Scores Classified as Grade Group 4 Prostate Cancer?