BACKGROUND: Previous cancer-specific mortality (CSM) analyses for different Gleason patterns in Gleason grade group (GGG) 5 cancer were limited by sample size. OBJECTIVE: To test for differences in CSM according to biopsy GG 5 patterns (4 + 5 vs 5 + 4 vs 5 + 5) among patients undergoing radical prostatectomy (RP) or external beam radiation therapy (EBRT). DESIGN, SETTING, AND PARTICIPANTS: Patients in the Surveillance, Epidemiology and End Results database treated with RP and EBRT (2004-2016) were identified and stratified according to Gleason 4 + 5 versus 5 + 4 versus 5 + 5. INTERVENTION: RP or EBRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Kaplan-Meier and multivariable Cox regression models predicting CSM were constructed. RESULTS AND LIMITATIONS: Of 17 263 eligible patients with GG 5 cancer at biopsy (RP: n = 7208; EBRT: n = 10 055), 12 705 had Gleason 4 + 5, 3302 had Gleason 5 + 4, and 1256 had Gleason 5 + 5 disease. Median age, prostate-specific antigen (PSA) at diagnosis, and advanced cT and cN stages significantly differed by Gleason pattern (Gleason 4 + 5 vs 5 + 4 vs 5 + 5; all p < 0.001). The 10-yr CSM rate was 18.2% for Gleason 4 + 5, 28.0% for Gleason 5 + 4, and 39.1% for Gleason 5 + 5 (p < 0.001). In multivariable analyses for the entire cohort adjusted for PSA, age at diagnosis, and cT and cN stage, Gleason 5 + 4 and Gleason 5 + 5 were associated with 1.6- and 2.2-fold higher CSM, respectively, relative to Gleason 4 + 5. In addition, Gleason 5 + 4 and Gleason 5 + 5 were associated with 1.6- and 2.5-fold, and 1.5- and 2.1-fold higher CSM rates in the RP and EBRT subgroups, respectively, relative to Gleason 4 + 5 (all p < 0.001). CONCLUSIONS: For patients with biopsy GG 5 prostate cancer treated with RP or EBRT, there are important CSM differences by Gleason pattern (4 + 5 vs 5 + 4 vs 5 + 5). Ideally, the individual Gleason pattern should be considered in pretreatment risk stratification. PATIENT SUMMARY: For patients with grade 5 prostate cancer, we found differences in cancer-specific death rates according to the pattern of abnormal cells in the prostate, called the Gleason score. The highest death rate was found for a Gleason pattern score of 5 + 5, followed by Gleason 5 + 4 and then Gleason 4 + 5. These differences were observed for both patients who were treated with prostate removal and patients who underwent radiotherapy.

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

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montréal Health Center Montréal Canada; Department of Urology Policlinico San Martino Hospital University of Genova Genova Italy

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montréal Health Center Montréal Canada; Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany

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

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Weill Cornell Medical College New York NY USA; Department of Urology University of Texas Southwestern Dallas TX USA; Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic; Institute for Urology and Reproductive Health 1 M Sechenov 1st Moscow State Medical University Moscow Russia; Division of Urology Department of Special Surgery Jordan University Hospital The University of Jordan Amman Jordan

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

Department of Urology University Hospital Frankfurt Frankfurt am Main Germany

Department of Urology University Hospital Frankfurt Frankfurt am Main Germany; Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montréal Health Center Montréal Canada

Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany

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

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