. 2024 Apr;2(4):e00032.

doi: 10.1097/ju9.0000000000000138. Epub 2024 Apr 15.

Expert Perspectives on Controversies in Metastatic Castration-Resistant Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 2

Alan H Bryce¹, E David Crawford², Neeraj Agarwal³, Maha H Hussain⁴, Himisha Beltran⁵, Matthew R Cooperberg⁶, Daniel P Petrylak⁷, Neal Shore⁸, Daniel E Spratt⁹, Scott T Tagawa¹⁰, Emmanuel S Antonarakis¹¹, Ana M Aparicio¹², Andrew J Armstrong¹³, Thomas P Boike¹⁴, Jeremie Calais¹⁵, Michael A Carducci¹⁶, Brian F Chapin¹⁷, Michael S Cookson¹⁸, John W Davis¹⁷, Tanya Dorff¹⁹, Scott E Eggener²⁰, Felix Y Feng²¹, Martin Gleave²², Celestia Higano²³, Andrei Iagaru²⁴, Alicia K Morgans²⁵, Michael Morris²⁶, Katie S Murray²⁷, Wendy Poage²⁸, Matthew B Rettig^{29

30}, Oliver Sartor³¹, Howard I Scher²⁶, Paul Sieber³², Eric Small³³, Sandy Srinivas³⁴, Evan Y Yu³⁵, Tian Zhang³⁶, Phillip J Koo³⁷

Affiliations

¹ Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, Arizona.
² Department of Urology, University of California San Diego, La Jolla, California.
³ Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
⁴ Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Evanston, Illinois.
⁵ Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
⁶ Department of Urology, University of California at San Francisco, San Francisco, California.
⁷ Yale New Haven Health, New Haven, Connecticut.
⁸ Carolina Urologic Research Center/Genesis Care, Myrtle Beach, South Carolina.
⁹ University Hospitals Seidman Cancer Center, Cleveland, Ohio.
¹⁰ Division of Hematology & Medical Oncology, Weill Cornell Medicine, New York, New York.
¹¹ Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
¹² Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
¹³ Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, North Carolina.
¹⁴ Michigan Healthcare Professionals, Troy, Michigan.
¹⁵ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California.
¹⁶ Hopkins Kimmel Cancer Center, Baltimore, Maryland.
¹⁷ Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
¹⁸ Department of Urology, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma.
¹⁹ City of Hope Comprehensive Cancer Center, Duarte, California.
²⁰ Departments of Surgery (Urology), University of Chicago Medical Center, Chicago, Illinois.
²¹ Departments of Radiation Oncology, Urology, and Medicine, University of California San Francisco, San Francisco, California.
²² Urological Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada.
²³ University of British Columbia, Vancouver, British Columbia, Canada.
²⁴ Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, Stanford, California.
²⁵ Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
²⁶ Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
²⁷ Department of Urology, NYU Langone Health, New York, New York.
²⁸ Prostate Conditions Education Council, Centennial, Colorado.
²⁹ Department of Medicine, Division of Hematology-Oncology, VA Greater Los Angeles, Los Angeles, California.
³⁰ Departments of Medicine and Urology, David Geffen School of Medicine at UCLA, Los Angeles, California.
³¹ Tulane Cancer Center, New Orleans, Louisiana.
³² Keystone Urology Specialists, Lancaster, Pennsylvania.
³³ UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California.
³⁴ Division of Medical Oncology, Stanford University Medical Center, Stanford, California.
³⁵ Department of Medicine, Division of Hematology & Oncology, University of Washington and Fred Hutchinson Cancer Center, Seattle, Washington.
³⁶ Division of Hematology and Oncology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas.
³⁷ Banner MD Anderson Cancer Center, Phoenix, Arizona.

PMID: 38774467
PMCID: PMC11107999
DOI: 10.1097/ju9.0000000000000138

Expert Perspectives on Controversies in Metastatic Castration-Resistant Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 2

Alan H Bryce et al. JU Open Plus. 2024 Apr.

. 2024 Apr;2(4):e00032.

doi: 10.1097/ju9.0000000000000138. Epub 2024 Apr 15.

Authors

Affiliations

¹ Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, Arizona.
² Department of Urology, University of California San Diego, La Jolla, California.
³ Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
⁴ Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Evanston, Illinois.
⁵ Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
⁶ Department of Urology, University of California at San Francisco, San Francisco, California.
⁷ Yale New Haven Health, New Haven, Connecticut.
⁸ Carolina Urologic Research Center/Genesis Care, Myrtle Beach, South Carolina.
⁹ University Hospitals Seidman Cancer Center, Cleveland, Ohio.
¹⁰ Division of Hematology & Medical Oncology, Weill Cornell Medicine, New York, New York.
¹¹ Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
¹² Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
¹³ Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, North Carolina.
¹⁴ Michigan Healthcare Professionals, Troy, Michigan.
¹⁵ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California.
¹⁶ Hopkins Kimmel Cancer Center, Baltimore, Maryland.
¹⁷ Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
¹⁸ Department of Urology, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma.
¹⁹ City of Hope Comprehensive Cancer Center, Duarte, California.
²⁰ Departments of Surgery (Urology), University of Chicago Medical Center, Chicago, Illinois.
²¹ Departments of Radiation Oncology, Urology, and Medicine, University of California San Francisco, San Francisco, California.
²² Urological Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada.
²³ University of British Columbia, Vancouver, British Columbia, Canada.
²⁴ Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, Stanford, California.
²⁵ Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
²⁶ Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
²⁷ Department of Urology, NYU Langone Health, New York, New York.
²⁸ Prostate Conditions Education Council, Centennial, Colorado.
²⁹ Department of Medicine, Division of Hematology-Oncology, VA Greater Los Angeles, Los Angeles, California.
³⁰ Departments of Medicine and Urology, David Geffen School of Medicine at UCLA, Los Angeles, California.
³¹ Tulane Cancer Center, New Orleans, Louisiana.
³² Keystone Urology Specialists, Lancaster, Pennsylvania.
³³ UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California.
³⁴ Division of Medical Oncology, Stanford University Medical Center, Stanford, California.
³⁵ Department of Medicine, Division of Hematology & Oncology, University of Washington and Fred Hutchinson Cancer Center, Seattle, Washington.
³⁶ Division of Hematology and Oncology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas.
³⁷ Banner MD Anderson Cancer Center, Phoenix, Arizona.

PMID: 38774467
PMCID: PMC11107999
DOI: 10.1097/ju9.0000000000000138

Abstract

Background: Management strategies for metastatic castration-resistant prostate cancer (mCRPC) have rapidly shifted in recent years. As novel imaging and therapeutic approaches have made their way to the clinic, providers are encountering increasingly challenging clinical scenarios, with limited guidance from the current literature.

Materials and methods: The US Prostate Cancer Conference (USPCC) is a multidisciplinary meeting of prostate cancer experts intended to address the many challenges of prostate cancer management. At the first annual USPCC meeting, areas of controversy and consensus were identified during a 2-day meeting that included expert presentations, full-panel discussions, and postdiscussion responses to questions developed by the USPCC cochairs and session moderators.

Results: This narrative review covers the USPCC expert discussion and perspectives relevant to mCRPC, including neuroendocrine/aggressive-variant prostate cancer (NEPC/AVPC). Areas of broad agreement identified among USPCC experts include the benefits of poly (ADP-ribose) polymerase (PARP) inhibitors for patients with BRCA1/2 mutations, the use of radioligand therapy in patients with prostate-specific membrane antigen (PSMA)-positive mCRPC, and the need for clinical trials that address real-world clinical questions, including the performance of novel therapies when compared with modern standard-of-care treatment. Ongoing areas of controversy and uncertainty included the appropriateness of PARP inhibitors in patients with non-BRCA1/2 mutations, the optimal definition of PSMA positivity, and systemic therapies for patients with NEPC/AVPC after progression on platinum-based therapies.

Conclusions: The first annual USPCC meeting identified several areas of controversy in the management of mCRPC, highlighting the urgent need for clinical trials designed to facilitate treatment selection and sequencing in this heterogeneous disease state.

Keywords: androgen antagonists; biomarkers; precision medicine; prostatic neoplasms; radiotherapy.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare the following competing interests: Alan H. Bryce has received compensation for a consulting or advisory role from Merck, Janssen, Astellas, AstraZeneca, Pfizer, Myovant, and Lantheus; and grant funding from Janssen. Andrew J. Armstrong has received compensation for a consulting or advisory role from Astellas, Epic Sciences, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Clovis, Exact Sciences, Myovant, Exelixis, GoodRx, and Novartis; and his institution has received research funding from Astellas, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Amgen, and Novartis. Andrei Iagaru has received compensation for a consulting or advisory role from Alpha9Tx, Clarity Pharmaceuticals, Novartis, Progenics, Radionetics, RayzeBio, and Telix; and research/grant funding from GE Healthcare and Novartis. Ana M. Aparicio has received compensation for a consulting or advisory role from Pfizer, Janssen, and Bristol Myers Squibb. Alicia K. Morgans has received compensation for a consulting or advisory role from Astellas, AstraZeneca, AAA, Bayer, Janssen, Exelixis, Myovant, Myriad Genetics, Lantheus, Novartis, Merck, Pfizer, Telix, and Sanofi; and research funding from Bayer, Astellas, Myovant, Pfzer, Sanofi, and Janssen. Brian F. Chapin has received compensation for a consulting or advisory role from Blue Earth Diagnostics, Astellas, Pfizer, and Janssen; and is a clinical trial investigator for Regeneron and Blue Earth Therapeutics. Daniel P. Petrylak has received compensation for a consulting or advisory role from Ada Cap (Advanced Accelerator Applications), Amgen, Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Exelixis, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Ipsen, Janssen, Merck & Company Inc, Mirati, Monopteros, Pfizer, Pharmacyclics, Regeneron, Roche, Sanofi Aventis Pharmaceuticals, Seattle Genetics, and Urogen; has received grant support from Ada Cap (Advanced Accelerator Applications), Agensys Inc, Arvinas, Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology, Daiichi Sankyo Company Limited, Eisai, Eli Lilly, Endocyte, Ferring, Genentech, Gilead Sciences, Innocrin, MedImmune, Medivation, Merck, Mirati, Novartis, Pfizer, Progenics, Replimune, Roche, Sanofi Aventis, and Seattle Genetics; and has owned stock in Bellicum and Tyme. Daniel E. Spratt has received compensation for a consulting or advisory role from AstraZeneca, Bayer, Boston Scientific, Elekta, Janssen, Novartis, Pfizer, and Varian. Emmanuel S. Antonarakis has received compensation for a consulting or advisory role from Sanofi, Dendreon, Janssen Biotech, ESSA, Merck, AstraZeneca, Clovis Oncology, Lilly, Bayer, Amgen, Astellas Pharma, Blue Earth Diagnostics, Bristol Myers Squibb/Celgene, Constellation Pharmaceuticals, Curium Pharma, Exact Sciences, Foundation Medicine, GlaxoSmithKline, InVitae, Ismar Health Care, Medivation, Tempus, Orion, and Alkido Pharma; he has received research funding from Celgene and Clovis Oncology; his institution has received research funding from Janssen Biotech, Johnson & Johnson, Sanofi, Dendreon, Aragon Pharmaceuticals, Exelixis, Millennium, Genentech, Novartis, Astellas Pharma, Tokai Pharmaceuticals, Merck, AstraZeneca, Clovis Oncology, Constellation Pharmaceuticals, Celgene, and Clovis Oncology; and he is co-inventor of a biomarker technology that has been licensed to Qiagen. E. David Crawford has received compensation for a consulting or advisory role from Janssen, Bayer, MDx, Tolmar, Pfizer, and Astellas; has received research/grant funding from the NIH and University of Colorado Cancer Center; and has received compensation for a leadership position from Carden Jennings. Eric Small has received compensation for a consulting or advisory role from Janssen, Fortis, and Deciphera; received honoraria from Janssen and Johnson & Johnson; and owns stock/stock options in Fortis, Harpoon, and Teon. Evan Y. Yu has received compensation for a consulting or advisory role from Aadi Bioscience, Advanced Accelerator Applications, Bayer, Janssen, Merck, and Oncternal; and his institution has received research funding from Bayer, Blue Earth, Daiichi-Sankyo, Dendreon, Lantheus, Merck, Seagen, Surface, Taiho, and Tyra. Felix Y. Feng has received compensation for a consulting or advisory role from Astellas, Bayer, Blue Earth Diagnostics, Janssen, Myovant, Novartis, Roivant, Sanofi, Tempus, Artera, BMS (Tumor Microenvironment Group), ClearNote, and Serimmune, Himisha Beltran has received compensation for a consulting or advisory role from Janssen, Merck, Pfizer, Foundation Medicine, Blue Earth Diagnostics, Amgen, Bayer, Oncorus, LOXO, Daicchi Sankyo, Sanofi, Curie Therapeutics, Fusion Pharma, Astra Zeneca, and Novartis; and her institution has received research funding from Janssen, Bristol Myers Squibb, Circle Pharma, Daicchi Sankyo, and Novartis. Jeremie Calais has received compensation for a consulting, advisory, or blinded image reading role from Advanced Accelerator Applications, Amgen, Astellas, Bayer, Blue Earth Diagnostics Inc, Curium Pharma, DS Pharma, GE Healthcare, Isoray, IBA RadioPharma, Janssen Pharmaceuticals, Monrol, Lightpointmedical, Lantheus, Novartis, Pfizer, POINT biopharma, Progenics, Radiomedix, Sanofi, Siemens-Varian, SOFIE, and Telix Pharmaceuticals; and grant funding from the Prostate Cancer Foundation. John W. Davis has received research funding from Janssen. Katie S. Murray has received compensation for a consulting or advisory role from Curium and Urogen Pharma. Michael S. Cookson has received compensation for a consulting or advisory role from LynxDx, Natera, Bayer, Consulting JW, Remedica Medical Education & Publishing, Pfizer, Lantheus, Nonagen Bioscience Corp, MJH LifeSciences, Pacific Edge Diagnostics USA Ltd, Janssen, Prokarium, BioPharm Communications, Myovant, Merck, Clinical Education Alliance, TesoRx Pharma; and has received research support from Ferring Pharmaceuticald and MDXHealth. Maha H. Hussain has received compensation for a consulting or advisory role from GSK, Novartis, and Bayer; honoraria for educational event or lecture from Merck, Mubarak Mahdi Almansour (Chairman, International Genitourinary Cancer Conference), MJH, and Academic CME; her institution has received research/grant funding from AstraZeneca and Arvinas. Michael Morris has received compensation for a consulting or advisory role from AstraZeneca, Lantheus, Daiichi, Convergent Therapeutics, Pfizer, ITM Isotope Technologies, Clarity Pharmaceuticals, Blue Earth Diagnostics, POINT Biopharma, Telix, and Z-Alpha; he is an uncompensated advisor to Bayer and Novartis; his institution has received research funding from Bayer, Corcept, Roche, Janssen, Celgene, Novartis, and Astellas. Matthew B. Rettig has received compensation for a consulting or advisory role from Myovant, INmune Bio, Bayer, and Johnson & Johnson; is a member of the Speakers’ Bureau for Johnson & Johnson and Bayer; and has received grants/research support from Merck, Lantheus, Progenics, Clovis, ORIC, Pfizer, Novartis, Amgen. Neeraj Agarwal has received compensation for a consulting or advisory role from Astellas, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, and Seattle Genetics; his institution has received research funding from Arnivas, Astellas, Astra Zeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Crispr, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Lava, Medivation, Merck, Nektar, Neoleukin, New Link Genetics, Novartis, Oric, Pfizer, Prometheus, Rexahn, Roche, Sanofi, Seattle Genetics, Takeda, and Tracon. Neal Shore has received compensation for a consulting or advisory role from AbbVie, Alessa Therapeutics, Akido, Amgen, Arquer, Asieris, Astellas, Astra Zeneca, Bayer, BMS, Boston Scientific, Clarity, Clovis, Cold Genesys, Dendreon, Exact Images, Exact Sciences, FerGene, FIZE Medical, GConcology, GenesisCare, Genetech, Guardant, Ferring, Foundation Medicine, ImmunityBio, Incyte, Invitae, Janssen, Lantheus, Lilly, MDX, Merck, Minomic, Myovant, Myriad, NGM, Nonagen, Novartis, NYMOX, Pacific Edge, Photocure, Pfizer, PlatformQ, Profound, Promaxo, Propella, Protara, Sanofi, SesenBio, Speciality Networks, Telix, Tolmar, Urogen, Vaxiion, and Vessi; received payment for expert testimony from Ferring; and is on the board of Photocure. Oliver Sartor has received compensation for a consulting or advisory role from Advanced Accelerator Applications, Amgen, ART BioScience, Astellas Pharma, AstraZeneca, Bayer, Clarity Pharmaceuticals, EMD Serono, Fusion Pharmaceuticals, Isotopen Technologien, Janssen, MacroGenics, Novartis, Pfizer, Point Biopharma, Ratio, Sanofi, Telix Pharmaceuticals, and TeneoBio; he has stock or other ownership interested with AbbVie, Cardinal Health, Clarity Pharmaceuticals, Convergent, Eli Lilly, Fusion Pharmaceuticals, Point Biopharma, Ratio, Telix, and United Health Group; he has patents for Saposin C and receptors as targets for treatment of benign and malignant disorders (U.S. patent awarded January 23, 2007; patent no. 7,166,691); he has provided expert testimony for Sanofi; he has received reimbursement for travel, accommodations, or expenses from AstraZeneca, Bayer, Lantheus, and Sanofi; and his institution has received research/grant funding from Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, InVitae, Janssen, Lantheus, Merck, and Sanofi. Phillip J. Koo has received compensation for a consulting or advisory role from Lantheus, Blue Earth Diagnostics, Merck, Janssen, Pfizer, Astellas, AstraZeneca, Bayer, Novartis, Sanofi, Telix, and Curium. Scott E. Eggener has received compensation for a consulting or advisory role Candel Therapeutics, A3P Biomedical, Cellvax, MetasTx, OptumHealth, and Janssen. Sandy Srinivas has received compensation for a consulting or advisory role from Novartis and Janssen. Scott T. Tagawa has received compensation for a consulting or advisory role from Sanofi, Medivation, Astellas, Dendreon, Janssen, Genentech, Bayer, Endocyte, Eisai, Immunomedics, Karyopharm, Abbvie, Tolmar, Seattle Genetics, Amgen, Clovis, QED, Pfizer, AAA/Novartis, Clarity, Genomic Health, POINT Biopharma, Blue Earth, AIkido Pharma, Telix Pharma, Convergent Therapeutics, EMD Serono, Myovant, Merck, Daiichi Sankyo, TransThera, and Regeneron; he is an unpaid consultant for Atlab Pharma, Phosplatin Therapeutics, Amgen, and Ambrx; he and his institution hold patents for biomarkers for sacituzumab govitecan therapy (Immunomedics/Gilead); and his institution has received research funding from Sanofi, Medivation, Astellas, Janssen, Amgen, Progenics, Dendreon, Lilly, Genentech, Newlink, BMS, Inovio, AstraZeneca, Immunomedics, Aveo, Rexahn, Atlab, Boehringer Ingelheim, Millennium, Bayer, Merck, Abbvie, Karyopharm, Endocyte, Clovis, Seattle Genetics, Novartis, Gilead, POINT Biopharma, Ambrx, Clarity. Thomas P. Boike has received compensation for a consulting or advisory role from Lantheus, Myovant, Novartis, Pfizer, Janssen, Astellas, Blue Earth, AstraZeneca, Palette Life Sciences, and Boston Scientific. Tanya Dorff has received compensation for a consulting or advisory role from AstraZeneca, Bayer, Janssen, and Sanofi. Tian Zhang has received compensation for a consulting or advisory role from Merck, Exelixis, Sanofi-Aventis, Janssen, Astra Zeneca, Pfizer, Amgen, BMS, Dendreon, SeaGen, Eisai, Aveo, Bayer, and Eli Lilly; honoraria from MJH Associates, Vaniam, Aptitude Health, PlatformQ, IntegrityCE, PeerView, and WJ Weiser; and her institution has received research funding from Novartis, Merck, Janssen, Astra Zeneca, Pfizer, Tempus, and Eli Lilly. Wendy Poage is an employee of Servier Pharmaceuticals; and she has ownership interests in 3D biopsy.

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Expert Perspectives on Controversies in Metastatic Castration-Resistant Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 2

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Expert Perspectives on Controversies in Metastatic Castration-Resistant Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 2

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