Pattern of Biopsy Gleason Grade Group 5 (4 + 5 vs 5 + 4 vs 5 + 5) Predicts Survival After Radical Prostatectomy or External Beam Radiation Therapy

Previous cancer-specific mortality (CSM) analyses for different Gleason patterns in Gleason grade group (GGG) 5 cancer were limited by sample size. 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). 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. RP or EBRT. Kaplan-Meier and multivariable Cox regression models predicting CSM were constructed. 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). 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. 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. For patients with Gleason grade group 5 cancer at biopsy, the group with Gleason 5 + 5 disease had the highest 10-yr cancer-specific mortality, followed by Gleason 5 + 4 and then Gleason 4 + 5. Risk stratification according to Gleason pattern should be considered before treatment for