Trial Design and Objectives for Patients With Prostate Cancer: Recommendations From the Prostate Cancer Working Group 4
Abstract
PURPOSE The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer. Methods We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer. RESULTS PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)–defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. CONCLUSION PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator–naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (68)
Andrew J. Armstrong
Michael J. Morris
Department of Medicine, Memorial Sloan Kettering Cancer Center
Wassim Abida
Department of Medicine, Memorial Sloan Kettering Cancer Center
Rahul R. Aggarwal
San Francisco Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA
Emmanuel S. Antonarakis
Masonic Cancer Center, University of Minnesota
Gerhardt Attard
Himisha Beltran
Alan Bryce
City of Hope Cancer Center, Goodyear, AZ
Michael A. Carducci
Johns Hopkins, Baltimore, MD
Heather H. Cheng
University of Washington, Seattle, WA
Delphine L. Chen
Fred Hutch Cancer Center, Seattle, WA
Kim N. Chi
Daniel S. Childs
William Dahut
American Cancer Society, Atlanta, GA
Louise Emmett
Karim Fizazi
Centre Oscar Lambret, University of Paris-Saclay, Lille, France
Andrei Gafita
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD
Daniel J. George
Duke Cancer Institute, Duke University School of Medicine, Durham, NC
Ken Hermann
2Department of Nuclear Medicine, University Hospital Essen, Essen, Germany, Essen, Germany
Michael S. Hofman
Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
Thomas Hope
University of California, San Francisco, San Francisco, CA
Maha Hussain
W. Kevin Kelly
Sidney Kimmel School of Medicine at Thomas Jefferson University, Philadelphia, PA
Elizabeth Kessler
University of Colorado School of Medicine, Aurora, CO
Phillip H. Kuo
Department of Radiology, City of Hope National Medical Center, Duarte, CA
Joshua Lang
University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, WI
Glenn Liu
University of Wisconsin Carbone Cancer Center, University of Wisconsin, Madison, WI
Catherine H. Marshall
Alicia K. Morgans
Dana-Farber Cancer Institute, Boston, MA
Rana R. McKay
Department of Medicine, Urology, and Radiation Medicine and Applied Sciences University of California‐San Diego La Jolla California USA
David Nanus
Weill Cornell Medicine, New York, NY
Peter Nelson
Fred Hutch Cancer Center, Seattle, WA
Channing Paller
Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD
Zachery R. Reichert
Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI
Charles J. Ryan
Memorial Sloan Kettering Cancer Center, New York, NY
A. Oliver Sartor
Transformational Prostate Cancer Research Center, LCMC Health, New Orleans, LA
Heiko Schoder
1memorial Sloan Kettering, NYC, United States
Lawrence H. Schwartz
Nima Sharifi
Walter M. Stadler
City of Hope Cancer Center, Chicago, IL
Mark Stein
Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY
Cora N. Sternberg
Andrew J. Armstrong, MD, ScM, FACP, Division of Medical Oncology, Department of Medicine, Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, Durham, NC; Arun A. Azad, MBBS, PhD; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia; Fred Saad, MD, University of Montreal Hospital Center, Montreal, QC, Canada; Maha Hussain, MD, FACP, FASCO, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL; Taro Iguchi, MD, PhD, Department of Urology, Kanazawa Medical University, Ishikawa, Japan; Arnulf Stenzl, MD, Department of Urology, University of Tübingen, Tübingen, Germany; and Cora N. Sternberg, MD, FACP, Englander Institute for Precision Medicine, Meyer Cancer Center, Weill Cornell Medicine, New York, NY
Russell Z. Szmulewitz
Department of Medicine, University of Chicago, Chicago, IL
Scott T. Tagawa
Weill Cornell Medical Center, NewYork Presbyterian Hospital, New York, NY
Alexandra O. Sokolova
Hematology Oncology, Oregon Health and Science University, Portland, OR
Alex W. Wyatt
Kosj Yamoah
Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Evan Y. Yu
Fred Hutchinson Cancer Center, University of Washington, Seattle, WA
Susan Halabi
From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) — all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana–Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) — both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) — both in...
Howard I. Scher
Memorial Sloan Kettering Cancer Center, New York, NY
Joshi J. Alumkal
Rogel Cancer Center, University of Michigan, Ann Arbor, MI
Ana Aparicio
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Pedro Barata
Charles Drake
Julie Graff
Anis A. Hamid
Elisabeth I. Heath
Department of Medical Oncology, Mayo Clinic Rochester, Rochester, MN
Jones Nauseef
Daniel Lage
Nadine Mallak
Akash Patnaik
Kristofer Prepelica
Dana E. Rathkopf
Matthew Rettig
Department of Medical Oncology, University of Southern California, Los Angeles, Los Angeles, CA
Steven P. Rowe
Susan F. Slovin
Memorial Sloan Kettering Cancer Center, New York, NY
Mary-Ellen Taplin
Dana–Farber Cancer Institute, Boston
Nicholas Zorko