NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Prostate Cancer Version 4.2019 — August 19, 2019 NCCN.org NCCN Guidelines for Patients® available at www.nccn.org/patients Continue Version 4.2019, 08/19/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 4.2019 Table of Contents Prostate Cancer Discussion *James L. Mohler, MD/Chair ω Celestia S. Higano, MD, FACP † ω Thomas J. Pugh, MD § Roswell Park Cancer Institute Fred Hutchinson Cancer Research Center/ University of Colorado Cancer Center Seattle Cancer Care Alliance Sandy Srinivas, MD/Vice Chair † Sylvia Richey, MD † Stanford Cancer Institute Eric Mark Horwitz, MD § St. Jude Children’s Research Hospital/The Fox Chase Cancer Center University of Tennessee Health Science Center Emmanuel S. Antonarakis, MD † The Sidney Kimmel Comprehensive Joseph E. Ippolito, MD, PhD ф Mack Roach, III, MD § Cancer Center at Johns Hopkins Siteman Cancer Center at Barnes- UCSF Helen Diller Family Jewish Hospital and Washington Comprehensive Cancer Center Andrew J. Armstrong, MD † University School of Medicine Duke Cancer Institute Stan Rosenfeld ¥ Christopher J. Kane, MD ω University of California San Francisco Anthony Victor D’Amico, MD, PhD § UC San Diego Moores Cancer Center Patient Services Committee Chair Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts Michael R. Kuettel, MD, MBA, PhD § Edward Schaeffer, MD, PhDω General Hospital Cancer Center Roswell Park Cancer Institute Robert H. Lurie Comprehensive Cancer Center of Northwestern University Brian J. Davis, MD, PhD § Joshua M. Lang, MD † Mayo Clinic Cancer Center University of Wisconsin Carbone Cancer Center Ahmad Shabsigh, MD ω The Ohio State University Comprehensive *Tanya Dorff, MD † Jesse McKenney, MD ≠ Cancer Center - James Cancer Hospital City of Hope National Cancer Center Case Comprehensive Cancer Center/ and Solove Research Institute James A. Eastham, MD ω University Hospitals Seidman Cancer Center and Memorial Sloan Kettering Cancer Center Cleveland Clinic Taussig Cancer Institute *Eric J. Small, MD † UCSF Helen Diller Family ≠ James A. Eastham, MD ω George Netto, MD Comprehensive Cancer Center Memorial Sloan Kettering Cancer Center O'Neal Comprehensive Cancer Center at UAB *Daniel E. Spratt, MD § ω Charles A. Enke, MD § David F. Penson, MD, MPH University of Michigan Fred & Pamela Buffett Cancer Center Vanderbilt-Ingram Cancer Center Rogel Cancer Center Thomas A. Farrington ¥ Elizabeth R. Plimack, MD, MS † Þ Jonathan Tward, MD, PhD § Prostate Health Education Network (PHEN) Fox Chase Cancer Center Huntsman Cancer Institute Julio M. Pow-Sang, MD ω at the University of Utah Moffitt Cancer Center NCCN Deborah Freedman-Cass, PhD ф Diagnostic/Interventional ¥ Patient advocate Dorothy A. Shead, MS radiology § Radiotherapy/Radiation oncology Continue Þ Internal medicine ω Urology NCCN Guidelines Panel Disclosures † Medical oncology * Discussion Section Writing ≠ Pathology Committee Version 4.2019, 08/19/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 4.2019 Table of Contents Prostate Cancer Discussion NCCN Prostate Cancer Panel Members Principles of Life Expectancy Estimation (PROS-A) Clinical Trials: NCCN believes Summary of Guidelines Updates Principles of Imaging (PROS-B) that the best management for any Initial Prostate Cancer Diagnosis (PROS-1) Principles of Active Surveillance and Observation patient with cancer is in a clinical Initial Risk Stratification and Staging Workup for (PROS-C) trial. Clinically Localized Disease (PROS-2) Principles of Radiation Therapy (PROS-D) Participation in clinical trials is Very Low Risk Group (PROS-4) Principles of Surgery (PROS-E) especially encouraged. Low Risk Group (PROS-5) Principles of Androgen Deprivation Therapy (PROS-F) To find clinical trials online at Favorable Intermediate Risk Group (PROS-6) Principles of Immunotherapy and Chemotherapy NCCN Member Institutions, click (PROS-G) here:nccn.org/clinical_trials/ Unfavorable Intermediate Risk Group (PROS-7) clinicians.aspx. High or Very High Risk Group (PROS-8) Staging (ST-1) NCCN Categories of Genetic and Molecular Biomarker Analysis for Evidence and Consensus: All Advanced Prostate Cancer (PROS-9) recommendations are category 2A Regional Risk Group (PROS-10) unless otherwise indicated. Monitoring (PROS-11) See NCCN Categories of Evidence and Consensus. Radical Prostatectomy PSA Persistence/Recurrence (PROS-12) Radiation Therapy Recurrence (PROS-13) Systemic Therapy for Castration-Naive Disease (PROS-14) Systemic Therapy for M0 Castration-Resistant Prostate Cancer (CRPC) (PROS-15) Systemic Therapy for M1 CRPC (PROS-16) Subsequent Systemic Therapy for M1 CRPC: No Visceral Metastases (PROS-17) Systemic Therapy for M1 CRPC: Visceral Metastases (PROS-18) The NCCN Guidelines® are a statement of evidence and consensus of the authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the NCCN Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network® (NCCN®) makes no representations or warranties of any kind regarding their content, use or application and disclaims any responsibility for their application or use in any way. The NCCN Guidelines are copyrighted by National Comprehensive Cancer Network®. All rights reserved. The NCCN Guidelines and the illustrations herein may not be reproduced in any form without the express written permission of NCCN. ©2019. Version 4.2019, 08/19/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 4.2019 Table of Contents Prostate Cancer Discussion Updates in Version 4.2019 of the NCCN Guidelines for Prostate Cancer from Version 3.2019 include: Discussion • The Discussion section was updated to reflect the changes in the algorithm. Updates in Version 3.2019 of the NCCN Guidelines for Prostate Cancer from Version 2.2019 include: PROS-14 improved OS over ADT alone. Adverse events that were more common • Systemic therapy for castration-naive disease: with apalutamide than with placebo included rash, hypothyroidism, and Added apalutamide as a (category 1) option for M1 prostate cancer. ischemic heart disease. Added enzalutamide as a (category 1) option for M1 prostate cancer. An open-label randomized phase 3 clinical trial of enzalutamide plus ADT PROS-15 in men with castration-naïve metastatic prostate cancer demonstrated • Systemic therapy for M0 castration-resistant prostate cancer (CRPC): improved OS over ADT alone. In a separate double-blind randomized Added darolutamide as a (category 1) option for patients with PSADT ≤10 phase 3 clinical, enzalutamide reduced the risk of metastatic progression mo. or death compared with placebo. Adverse events associated with PROS-F (2 of 5) enzalutamide included fatigue, seizures, and hypertension. • Modified treatment options for men with M1 castration-naive disease: • Added darolutamide (for M0 and PSADT ≤10 mo). Orchiectomy plus abiraterone, enzalutamide, or apalutamide • Added a new bullet: A phase 3 study of patients with M0 CRPC and a LHRH agonist (as above) plus abiraterone, enzalutamide, or apalutamide PSADT ≤10 mo showed darolutamide (600 mg twice daily) improved LHRH antagonist (as above) plus abiraterone, enzalutamide, or the primary endpoint of metastasis-free survival over placebo (40.4 mo apalutamide vs. 18.4 mo). An improvement in overall survival was seen at the first PROS-F (3 of 5) interim analysis (HR for death, 0.71; 95% CI, 0.50-0.99; P = .045), although • Added the following 3 new bullets: these data are immature (median survival was not reached in either Two randomized phase 3 clinical trials of abiraterone with prednisone arm). Adverse events that occurred more frequently in the treatment arm plus ADT in men with castration-naïve metastatic prostate cancer included fatigue (12.1% vs. 8.7%), pain in an extremity (5.8% vs. 3.2%), demonstrated improved OS over ADT alone. Adverse events were higher and rash (2.9% vs. 0.9%). The incidence of fractures was similar between with abiraterone and prednisone but were generally mild in nature and darolutamide and placebo (4.2% vs. 3.6%). were largely related to mineralocorticoid excess (ie, hypertension, hypokalemia, edema), hormonal effects (ie, fatigue, hot flushes), and liver toxicity. Cardiac events, severe hypertension, and liver toxicity were increased with abiraterone. A double-blind randomized phase 3 clinical trial of apalutamide plus ADT in men with castration-naïve metastatic prostate cancer demonstrated Version 4.2019, 08/19/19 © 2019 National Comprehensive Cancer Network® (NCCN®), All rights reserved. NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN. NCCN Guidelines Index NCCN Guidelines Version 4.2019 Table of Contents Prostate Cancer Discussion Updates in Version 2.2019 of the NCCN Guidelines for Prostate Cancer from