Eric A Klein1, María Santiago-Jiménez2, Kasra Yousefi2, Bruce A Robbins3, Edward M Schaeffer4, Bruce J Trock5, Jeffrey Tosoian5, Zaid Haddad2, Seong Ra3, R Jeffrey Karnes6, Robert B Jenkins7, John C Cheville7, Robert B Den8, Adam P Dicker8, Elai Davicioni2, Stephen J Freedland9, Ashley E Ross5. 1. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: kleine@ccf.org. 2. GenomeDx Biosciences, Vancouver, British Columbia, Canada. 3. San Diego Pathology LLC, San Diego, California. 4. Department of Urology, Northwestern University, Evanston, Illinois. 5. The James Buchanan Brady Urological Institute, Johns Hopkins Hospital, Baltimore, Maryland. 6. Department of Urology, Mayo Clinic, Rochester, Minnesota. 7. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. 8. Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania. 9. Division of Urology, Department of Surgery, Center for Integrated Research on Cancer and Lifestyle, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, California; Surgery Section, Durham Veteran Affairs Medical Center, Durham, North Carolina.
Abstract
PURPOSE: We determined how frequently histological Gleason 3 + 3 = 6 tumors have the molecular characteristics of disease with metastatic potential. MATERIALS AND METHODS: We analyzed prostatectomy tissue from 337 patients with Gleason 3 + 3 disease. All tissue was re-reviewed in blinded fashion by genitourinary pathologists using 2005 ISUP (International Society of Urological Pathology) Gleason grading criteria. A previously validated Decipher® metastasis signature was calculated in each case based on a locked model. To compare patient characteristics across pathological Gleason score categories we used the Fisher exact test or the ANOVA F test. The distribution of Decipher scores among different clinicopathological groups was compared with the Wilcoxon rank sum test. The association of Decipher score with adverse pathology features was examined using logistic regression models. The significance level of all statistical tests was 0.05. RESULTS: Of men with Gleason 3 + 3 = 6 disease only 269 (80%) had a low Decipher score with intermediate and high scores in 43 (13%) and 25 (7%), respectively. Decipher scores were significantly higher among pathological Gleason 3 + 3 = 6 specimens from cases with adverse pathological features such as extraprostatic extension, seminal vesicle involvement or positive margins (p <0.001). The median Decipher score in patients with margin negative pT2 disease was 0.23 (IQR 0.09-0.42) compared to 0.30 (IQR 0.17-0.42) in patients with pT3 disease or positive margins (p = 0.005). CONCLUSIONS: Using a robust and validated prognostic signature we found that a small but not insignificant proportion of histological Gleason 6 tumors harbored molecular characteristics of aggressive cancer. Molecular profiling of such tumors at diagnosis may better select patients for active surveillance at diagnosis and trigger appropriate intervention during followup. Copyright Â
PURPOSE: We determined how frequently histological Gleason 3 + 3 = 6 tumors have the molecular characteristics of disease with metastatic potential. MATERIALS AND METHODS: We analyzed prostatectomy tissue from 337 patients with Gleason 3 + 3 disease. All tissue was re-reviewed in blinded fashion by genitourinary pathologists using 2005 ISUP (International Society of Urological Pathology) Gleason grading criteria. A previously validated Decipher® metastasis signature was calculated in each case based on a locked model. To compare patient characteristics across pathological Gleason score categories we used the Fisher exact test or the ANOVA F test. The distribution of Decipher scores among different clinicopathological groups was compared with the Wilcoxon rank sum test. The association of Decipher score with adverse pathology features was examined using logistic regression models. The significance level of all statistical tests was 0.05. RESULTS: Of men with Gleason 3 + 3 = 6 disease only 269 (80%) had a low Decipher score with intermediate and high scores in 43 (13%) and 25 (7%), respectively. Decipher scores were significantly higher among pathological Gleason 3 + 3 = 6 specimens from cases with adverse pathological features such as extraprostatic extension, seminal vesicle involvement or positive margins (p <0.001). The median Decipher score in patients with margin negative pT2 disease was 0.23 (IQR 0.09-0.42) compared to 0.30 (IQR 0.17-0.42) in patients with pT3 disease or positive margins (p = 0.005). CONCLUSIONS: Using a robust and validated prognostic signature we found that a small but not insignificant proportion of histological Gleason 6 tumors harbored molecular characteristics of aggressive cancer. Molecular profiling of such tumors at diagnosis may better select patients for active surveillance at diagnosis and trigger appropriate intervention during followup. Copyright Â
Authors: Andrei S Purysko; Cristina Magi-Galluzzi; Omar Y Mian; Sarah Sittenfeld; Elai Davicioni; Marguerite du Plessis; Christine Buerki; Jennifer Bullen; Lin Li; Anant Madabhushi; Andrew Stephenson; Eric A Klein Journal: Eur Radiol Date: 2019-03-07 Impact factor: 5.315
Authors: Daniel E Spratt; Darlene L Y Dai; Robert B Den; Patricia Troncoso; Kasra Yousefi; Ashley E Ross; Edward M Schaeffer; Zaid Haddad; Elai Davicioni; Rohit Mehra; Todd M Morgan; Walter Rayford; Firas Abdollah; Edouard Trabulsi; Mary Achim; Elsa Li Ning Tapia; Mireya Guerrero; Robert Jeffrey Karnes; Adam P Dicker; Mark A Hurwitz; Paul L Nguyen; Felix F Y Feng; Stephen J Freedland; John W Davis Journal: Eur Urol Date: 2017-12-10 Impact factor: 20.096
Authors: Jonathan C Hu; Jeffrey J Tosoian; Ji Qi; Deborah Kaye; Anna Johnson; Susan Linsell; James E Montie; Khurshid R Ghani; David C Miller; Kirk Wojno; Frank N Burks; Daniel E Spratt; Todd M Morgan Journal: JCO Precis Oncol Date: 2018-10-19
Authors: Jeffrey J Tosoian; Liana B Guedes; Carlos L Morais; Mufaddal Mamawala; Ashley E Ross; Angelo M De Marzo; Bruce J Trock; Misop Han; H Ballentine Carter; Tamara L Lotan Journal: Prostate Cancer Prostatic Dis Date: 2018-10-02 Impact factor: 5.554