BACKGROUND: We hypothesized that Gleason Grade Group (GGG) IV patients treated with radical prostatectomy (RP) or external beam radiotherapy (EBRT) exhibit different cancer-specific mortality (CSM) rates according to underlying Gleason patterns (GP): 4 + 4 versus 3 + 5 versus 5 + 3. MATERIALS AND METHODS: We identified all GGG IV patients treated with either RP or EBRT within the Surveillance, Epidemiology, and End Results 2004-2016 database. The effect of biopsy GP on CSM (3 + 5 vs. 4 + 4 vs. 5 + 3) was tested in Kaplan-Meier and multivariable competing risks regression models (adjusted for PSA, age at diagnosis, cT-, and cN-stage). RESULTS: Of 26,458 GGG IV patients, 14,203 (53.7%) were treated with EBRT and 12,255 (46.3%) with RP. Of RP patients, 15.3 versus 81.2 versus 3.4% exhibited biopsy GP 3 + 5 versus 4 + 4 versus 5 + 3 and respective 10-year CSM rates were 6.5 versus 6.2 versus 12.6% (p < .001). In multivariable analyses addressing RP patients, GP 5 + 3 was associated with two-fold higher CSM rate than GP 4 + 4 (p < .001), but not GP 3 + 5 (p = .1). Of EBRT patients, 7.6 versus 89.8 versus 2.6% exhibited biopsy GP 3 + 5 versus 4 + 4 versus 5 + 3 and respective 10-year CSM rates were 12.2 versus 13.8 versus 17.8% (p < .001). In multivariable analyses addressing EBRT patients, no CSM differences according to GP were observed (all p ≥ .4). CONCLUSION: In GGG IV RP candidates, the presence of biopsy GP 5 + 3 purports a significantly higher CSM than in GP 4 + 4 or 3 + 5. In GGG IV EBRT candidates, no significant CSM differences according to GP were recorded.

Department of Maternal Child and Urological Sciences Policlinico Umberto 1 Hospital Sapienza Rome University Rome Italy

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

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology Policlinico San Martino Hospital University of Genova Genova Italy

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University Hospital Frankfurt Frankfurt am Main Germany

Department of Urology University Hospital Hamburg Eppendorf Hamburg Germany

Department of Urology University of Texas Southwestern Dallas Texas USA

Departments of Urology Weill Cornell Medical College New York City New York USA

Division of Experimental Oncology Department of Urology Urological Research Institute IRCCS San Raffaele Scientific Institute Milan Italy

Division of Urology Cancer Prognostics and Health Outcomes Unit University of Montréal Health Center Montréal Québec Canada

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

Institute for Urology and Reproductive Health 1 M Sechenov 1st Moscow State Medical University Moscow Russia

Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany

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