National Cancer Institute's Working Group on Biochemically Recurrent Prostate Cancer: Clinical Trial Design Considerations
Abstract
PURPOSE Biochemical recurrence (BCR) of prostate cancer (PCa) after definitive surgery and/or radiation (including salvage strategies) is a burgeoning area of clinical research inspired by ultrasensitive next-generation imaging. Most phase III trials in PCa have focused on metastatic disease, defined by conventional imaging. Despite the emergence of new imaging, clinical trial principles from metastatic studies will not optimize future BCR trials. METHODS A Working Group convened at the National Cancer Institute on November 13, 2024 (NCI BCR WG). Key areas of discussion included nomenclature, baseline criteria for data capture, imaging considerations, delineation of high-risk populations to be targeted for trial development, requirements of metastasis-directed therapy (MDT) or hormonal therapy, quality-of-life considerations, and potential study end points. RESULTS The NCI BCR WG defined the novel term “prostate-specific membrane antigen (PSMA)+BCR” to identify the emerging concept of recurrent PCa identifiable only on PSMA positron emission tomography (PET), overlapping with BCR and distinct from metastatic hormone-sensitive PCa as traditionally defined by conventional imaging. The WG suggested defining high-risk BCR with a prostate-specific antigen doubling time of ≤6 months, regardless of PET findings. The WG provided recommendations for baseline data capture and imaging requirements. Neither systemic therapy nor MDT were considered mandatory for control arms. The WG also discussed novel end points and quality-of-life metrics in this disease space. CONCLUSION These discussions should inform future clinical BCR trials in this distinct disease space relative to metastatic disease defined by conventional imaging. The NCI BCR WG strongly advocates that future trials explore deintensification of treatment to minimize toxicity in this relatively indolent disease state.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (32)
David J. Einstein
Melissa L. Abel
Center for Cancer Research, National Cancer Institute, Bethesda, MD
Jeanny B. Aragon-Ching
Inova Schar Cancer Institute, Fairfax, VA
Philip M. Arlen
Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
Karen A. Autio
Memorial Sloan Kettering Cancer Center, New York, NY
Marijo Bilusic
University of Miami/Sylvester Comprehensive Cancer Center, Miami, FL
Michael A. Carducci
Johns Hopkins, Baltimore, MD
Peter L. Choyke
Deborah E. Citrin
Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD
William D. Figg
Julie N. Graff
Oregon Health & Science University, Portland, OR
James L. Gulley
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...
Fatima Karzai
Liza Lindenberg
National Institutes of Health, Bethesda, MD
Mark C. Markowski
Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD
Catherine H. Marshall
Douglas G. McNeel
Department of Medicine, University of Wisconsin, Madison, WI
Esther Mena
1National Cancer Institute, Lymphoid Malignancies Branch, Bethesda, United States
Helen Moon
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...
Russell K. Pachynski
Channing J. Paller
Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD
Krishnan R. Patel
Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
Edwin M. Posadas
Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA
Kenneth J. Pienta
Urology, Oncology, Pharmacology and Molecular Sciences, and Chemical and Biomolecular Engineering Cancer Ecology Center at the Brady Urological Institute Johns Hopkins University Baltimore Maryland USA
Meredith M. Regan
Dana-Farber Cancer Institute and IBCSG Statistical Center, Boston, MA
Laura A. Sena
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, Baltimore, MD
Charlotte S. Walmsley
Beth Israel Deaconess Medical Center, Boston, MA
Xiao X. Wei
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
Evan Y. Yu
Fred Hutchinson Cancer Center, University of Washington, Seattle, WA
Phuoc T. Tran
Ravi A. Madan
Center for Cancer Research, National Cancer Institute, Bethesda, MD