A multidisciplinary approach to address unmet needs in the management of patients with non-metastatic castration-resistant prostate cancer

A multidisciplinary approach to address unmet needs in the management of patients with non-metastatic castration-resistant prostate cancer

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ABSTRACT BACKGROUND With the availability of second-generation androgen receptor inhibitors (SGARIs), the treatment landscape has changed dramatically for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). In clinical trials, the SGARIs (apalutamide, enzalutamide, darolutamide) increased metastasis-free survival (MFS), overall survival (OS), and patient quality of life compared to placebo. These drugs were subsequently integrated into nmCRPC clinical practice guidelines. With advances in radiographic imaging, disease assessment, and patient monitoring, nmCRPC strategies are evolving to address limitations related to tracking disease progression using prostate-specific antigen (PSA) kinetics. METHODS A panel of 10 multidisciplinary experts in prostate cancer conducted reviews and discussions of unmet needs in the management and monitoring of patients with nmCRPC in order to develop consensus recommendations. RESULTS Across the SGARI literature, patient MFS and OS are generally comparable for all treatments, but important distinctions exist regarding short- and long-term drug safety profiles and drug-drug interactions. With respect to disease monitoring, a substantial proportion of patients using SGARIs may experience disease progression without rising PSA levels, suggesting a need for enhanced radiographic imaging in addition to PSA monitoring. Recent data also indicate that novel prostate-specific membrane antigen positron emission tomography radiotracers provide enhanced accuracy for disease detection, as compared to conventional imaging. CONCLUSIONS Clinical decision-making in nmCRPC has become more complex, with new opportunities to apply precision medicine to patient care. Multidisciplinary teams can ensure that patients with nmCRPC receive optimal and individualized disease management. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 4 print issues and online access $259.00 per year only $64.75 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS TREATMENT OF NONMETASTATIC CASTRATION-RESISTANT PROSTATE CANCER: FOCUS ON SECOND-GENERATION ANDROGEN RECEPTOR INHIBITORS Article Open access 08 February 2021 NAVIGATING THERAPEUTIC SEQUENCING IN THE METASTATIC CASTRATION-RESISTANT PROSTATE CANCER PATIENT JOURNEY Article Open access 17 October 2024 REAL-WORLD PATIENT CHARACTERISTICS ASSOCIATED WITH SURVIVAL OF 2 YEARS OR MORE AFTER RADIUM-223 TREATMENT FOR METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (EPIX STUDY) Article Open access 21 February 2022 CHANGE HISTORY * _ 20 APRIL 2024 A Correction to this paper has been published: https://doi.org/10.1038/s41391-024-00835-x _ REFERENCES * National Cancer Institute (NCI). 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FOCUS: Androgen receptor antagonists; castration-resistant prostate cancer; drug interactions; prostate-specific antigen; quality of life; safety. FUNDING This activity is supported by an independent medical education grant from Bayer for medical writing of this manuscript. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * GenesisCare US, Myrtle Beach, SC, USA Neal D. Shore * University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA Emmanuel S. Antonarakis * Northwestern University Feinberg School of Medicine, Chicago, IL, USA Ashley E. Ross * Johns Hopkins Medical Institutions, Baltimore, MD, USA Catherine H. Marshall * University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA Kelly L. Stratton, Adanma Ayanambakkam & Michael S. Cookson * University of California, San Diego, La Jolla, CA, USA Rana R. McKay * Mayo Clinic, Phoenix, AZ, USA Alan H. Bryce * Dana Farber Cancer Institute, Boston, MA, USA Marina D. Kaymakcalan Authors * Neal D. Shore View author publications You can also search for this author inPubMed Google Scholar * Emmanuel S. Antonarakis View author publications You can also search for this author inPubMed Google Scholar * Ashley E. Ross View author publications You can also search for this author inPubMed Google Scholar * Catherine H. Marshall View author publications You can also search for this author inPubMed Google Scholar * Kelly L. Stratton View author publications You can also search for this author inPubMed Google Scholar * Adanma Ayanambakkam View author publications You can also search for this author inPubMed Google Scholar * Michael S. Cookson View author publications You can also search for this author inPubMed Google Scholar * Rana R. McKay View author publications You can also search for this author inPubMed Google Scholar * Alan H. Bryce View author publications You can also search for this author inPubMed Google Scholar * Marina D. Kaymakcalan View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS EAS, CHM, and AER contributed to section 1—Metastatic Free Survival (MFS) Endpoint. KLS, MSC, and AA contributed to section 2—Safety/Tolerability. RRM and MDK contributed to section 3—Drug-Drug Interactions. AHB contributed to section 4—Patient Monitoring. All authors contributed to section 5—Current Challenges and Future Considerations. CORRESPONDING AUTHOR Correspondence to Neal D. Shore. ETHICS DECLARATIONS COMPETING INTERESTS NDS: Consulting fees: AbbVie, Alessa Therapeutics, Amgen, Arquer, Asieris, Astellas, Astra Zeneca, Bayer, BMS, Boston Scientific, Clarity, Dendreon, Exact Images, Ferring, FIZE Medical, GConcology, GenesisCare, Genetech, 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, Speciality Networks, Telix, Tolmar, Urogen, Vaxiion, Vessi; Payment for expert testimony: Ferring; Other financial or non-financial interests: Alessa, Photocure Board. ESA: Support for present the manuscript: Merck; Grants or contracts: Astellas, AstraZeneca, Bayer, Bristol Myers-Squibb, Celgene, Constellation Pharma, MacroGenics, Merck, Orion, Sanofi; Consulting fees: Aikido Pharma, Corcept Therapeutics, EcoR1, Foundation Medicine, Hookipa Pharma, Invitae, KeyQuest Health, Menarini Silicon Biosystems, z-Alpha; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: UroWebinar; Support for attending meetings and/or travel: MJH Events, Research to Practice, Sanofi; Patents planned, issued or pending: Qiagen; Participation on a Data Safety Monitoring Board or Advisory Board: Aadi Bioscience/CM Propel, Amgen; Board or Advisory Board: AstraZeneca, Bayer, Blue Earth Diagnostics, Ismar, Janssen, Merck, Sanofi. AHB: Support for present manuscript: Bayer; Grants or contracts: Astellas; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Merck, Pfizer, Janssen, Myovant, Astra Zeneca, Bayer, Astellas, Novartis; Support for attending meetings and/or travel: Pfizer, Bayer. RRM: Consulting fees: AstraZeneca, Aveo, Bayer, Bristol-Myers Squibb, Calithera, Caris, Dendreon, Eisai, Exelixis, Johnson & Johnson, Lilly, Merck, Myovant, Novartis, Pfizer, Sanofi, SeaGen, Sorrento Therapeutics, Telix, Tempus; Institutional research support: AstraZeneca, Bayer, Tempus, Oncternal, BMS, Exelixis. KLS: Grants or contracts: Dendreon Pharmaceuticals, Alliance Foundation Trials, Pfizer-B8011006, TulsaPRO – Perigon, Landmark Services, Janssen-pending, Merck Master Engagement, Medical Director, Surgery Center, Phase IB Trial of Relugolix and Enzalutamide as Neoadjuv; Consulting fees: Merck & Company Advisory-expired; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Bayer Speaker Bureau 2022, Carden Jennings Publishing, Elzevier, Ebix Oakstone, National Comprehensive Cancer Network, Society of Urologic Nurses & Associates, ARK Prostate Cancer Symposium; Support for attending meetings and/or travel: Tulsa Pro Perigon – Onsite Case Observation; American Urological Association; National Comprehensive Cancer Network; Participation on a Data Safety Monitoring Board or Advisory Board: Merck; Leadership or fiduciary role in other board, society, committee or advocacy group: Society of Urologic Oncology Trials Consortium – Board of Directors, Prostate Organ Site Comm; Johns Hopkins Medicine/Oakstone Publishing Practical Reviews in Urology; Society of Urologic Oncology-Clinical Trials Consortium Board Of Directors; Society of Urologic Oncology Young Urologic Oncologist. AA: Nothing to disclose. 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Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Shore, N.D., Antonarakis, E.S., Ross, A.E. _et al._ A multidisciplinary approach to address unmet needs in the management of patients with non-metastatic castration-resistant prostate cancer. _Prostate Cancer Prostatic Dis_ 28, 250–259 (2025). https://doi.org/10.1038/s41391-024-00803-5 Download citation * Received: 04 October 2023 * Revised: 23 January 2024 * Accepted: 26 January 2024 * Published: 02 March 2024 * Issue Date: June 2025 * DOI: https://doi.org/10.1038/s41391-024-00803-5 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

ABSTRACT BACKGROUND With the availability of second-generation androgen receptor inhibitors (SGARIs), the treatment landscape has changed dramatically for patients with nonmetastatic


castration-resistant prostate cancer (nmCRPC). In clinical trials, the SGARIs (apalutamide, enzalutamide, darolutamide) increased metastasis-free survival (MFS), overall survival (OS), and


patient quality of life compared to placebo. These drugs were subsequently integrated into nmCRPC clinical practice guidelines. With advances in radiographic imaging, disease assessment, and


patient monitoring, nmCRPC strategies are evolving to address limitations related to tracking disease progression using prostate-specific antigen (PSA) kinetics. METHODS A panel of 10


multidisciplinary experts in prostate cancer conducted reviews and discussions of unmet needs in the management and monitoring of patients with nmCRPC in order to develop consensus


recommendations. RESULTS Across the SGARI literature, patient MFS and OS are generally comparable for all treatments, but important distinctions exist regarding short- and long-term drug


safety profiles and drug-drug interactions. With respect to disease monitoring, a substantial proportion of patients using SGARIs may experience disease progression without rising PSA


levels, suggesting a need for enhanced radiographic imaging in addition to PSA monitoring. Recent data also indicate that novel prostate-specific membrane antigen positron emission


tomography radiotracers provide enhanced accuracy for disease detection, as compared to conventional imaging. CONCLUSIONS Clinical decision-making in nmCRPC has become more complex, with new


opportunities to apply precision medicine to patient care. Multidisciplinary teams can ensure that patients with nmCRPC receive optimal and individualized disease management. Access through


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CONTENT BEING VIEWED BY OTHERS TREATMENT OF NONMETASTATIC CASTRATION-RESISTANT PROSTATE CANCER: FOCUS ON SECOND-GENERATION ANDROGEN RECEPTOR INHIBITORS Article Open access 08 February 2021


NAVIGATING THERAPEUTIC SEQUENCING IN THE METASTATIC CASTRATION-RESISTANT PROSTATE CANCER PATIENT JOURNEY Article Open access 17 October 2024 REAL-WORLD PATIENT CHARACTERISTICS ASSOCIATED


WITH SURVIVAL OF 2 YEARS OR MORE AFTER RADIUM-223 TREATMENT FOR METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (EPIX STUDY) Article Open access 21 February 2022 CHANGE HISTORY * _ 20 APRIL


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https://www.drugs.com/drug_interactions.html. Download references ACKNOWLEDGEMENTS We acknowledge the contributions of Carden Jennings Publishing Co., Ltd., and medical writers Aimee Spevak


and Caitlin Rothermel in assisting in the preparation of this manuscript. FOCUS: Androgen receptor antagonists; castration-resistant prostate cancer; drug interactions; prostate-specific


antigen; quality of life; safety. FUNDING This activity is supported by an independent medical education grant from Bayer for medical writing of this manuscript. AUTHOR INFORMATION AUTHORS


AND AFFILIATIONS * GenesisCare US, Myrtle Beach, SC, USA Neal D. Shore * University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA Emmanuel S. Antonarakis * Northwestern University


Feinberg School of Medicine, Chicago, IL, USA Ashley E. Ross * Johns Hopkins Medical Institutions, Baltimore, MD, USA Catherine H. Marshall * University of Oklahoma Health Sciences Center,


Oklahoma City, OK, USA Kelly L. Stratton, Adanma Ayanambakkam & Michael S. Cookson * University of California, San Diego, La Jolla, CA, USA Rana R. McKay * Mayo Clinic, Phoenix, AZ, USA


Alan H. Bryce * Dana Farber Cancer Institute, Boston, MA, USA Marina D. Kaymakcalan Authors * Neal D. Shore View author publications You can also search for this author inPubMed Google


Scholar * Emmanuel S. Antonarakis View author publications You can also search for this author inPubMed Google Scholar * Ashley E. Ross View author publications You can also search for this


author inPubMed Google Scholar * Catherine H. Marshall View author publications You can also search for this author inPubMed Google Scholar * Kelly L. Stratton View author publications You


can also search for this author inPubMed Google Scholar * Adanma Ayanambakkam View author publications You can also search for this author inPubMed Google Scholar * Michael S. Cookson View


author publications You can also search for this author inPubMed Google Scholar * Rana R. McKay View author publications You can also search for this author inPubMed Google Scholar * Alan H.


Bryce View author publications You can also search for this author inPubMed Google Scholar * Marina D. Kaymakcalan View author publications You can also search for this author inPubMed 


Google Scholar CONTRIBUTIONS EAS, CHM, and AER contributed to section 1—Metastatic Free Survival (MFS) Endpoint. KLS, MSC, and AA contributed to section 2—Safety/Tolerability. RRM and MDK


contributed to section 3—Drug-Drug Interactions. AHB contributed to section 4—Patient Monitoring. All authors contributed to section 5—Current Challenges and Future Considerations.


CORRESPONDING AUTHOR Correspondence to Neal D. Shore. ETHICS DECLARATIONS COMPETING INTERESTS NDS: Consulting fees: AbbVie, Alessa Therapeutics, Amgen, Arquer, Asieris, Astellas, Astra


Zeneca, Bayer, BMS, Boston Scientific, Clarity, Dendreon, Exact Images, Ferring, FIZE Medical, GConcology, GenesisCare, Genetech, 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, Speciality


Networks, Telix, Tolmar, Urogen, Vaxiion, Vessi; Payment for expert testimony: Ferring; Other financial or non-financial interests: Alessa, Photocure Board. ESA: Support for present the


manuscript: Merck; Grants or contracts: Astellas, AstraZeneca, Bayer, Bristol Myers-Squibb, Celgene, Constellation Pharma, MacroGenics, Merck, Orion, Sanofi; Consulting fees: Aikido Pharma,


Corcept Therapeutics, EcoR1, Foundation Medicine, Hookipa Pharma, Invitae, KeyQuest Health, Menarini Silicon Biosystems, z-Alpha; Payment or honoraria for lectures, presentations, speakers


bureaus, manuscript writing or educational events: UroWebinar; Support for attending meetings and/or travel: MJH Events, Research to Practice, Sanofi; Patents planned, issued or pending:


Qiagen; Participation on a Data Safety Monitoring Board or Advisory Board: Aadi Bioscience/CM Propel, Amgen; Board or Advisory Board: AstraZeneca, Bayer, Blue Earth Diagnostics, Ismar,


Janssen, Merck, Sanofi. AHB: Support for present manuscript: Bayer; Grants or contracts: Astellas; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or


educational events: Merck, Pfizer, Janssen, Myovant, Astra Zeneca, Bayer, Astellas, Novartis; Support for attending meetings and/or travel: Pfizer, Bayer. RRM: Consulting fees: AstraZeneca,


Aveo, Bayer, Bristol-Myers Squibb, Calithera, Caris, Dendreon, Eisai, Exelixis, Johnson & Johnson, Lilly, Merck, Myovant, Novartis, Pfizer, Sanofi, SeaGen, Sorrento Therapeutics, Telix,


Tempus; Institutional research support: AstraZeneca, Bayer, Tempus, Oncternal, BMS, Exelixis. KLS: Grants or contracts: Dendreon Pharmaceuticals, Alliance Foundation Trials, Pfizer-B8011006,


TulsaPRO – Perigon, Landmark Services, Janssen-pending, Merck Master Engagement, Medical Director, Surgery Center, Phase IB Trial of Relugolix and Enzalutamide as Neoadjuv; Consulting fees:


Merck & Company Advisory-expired; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Bayer Speaker Bureau 2022, Carden


Jennings Publishing, Elzevier, Ebix Oakstone, National Comprehensive Cancer Network, Society of Urologic Nurses & Associates, ARK Prostate Cancer Symposium; Support for attending


meetings and/or travel: Tulsa Pro Perigon – Onsite Case Observation; American Urological Association; National Comprehensive Cancer Network; Participation on a Data Safety Monitoring Board


or Advisory Board: Merck; Leadership or fiduciary role in other board, society, committee or advocacy group: Society of Urologic Oncology Trials Consortium – Board of Directors, Prostate


Organ Site Comm; Johns Hopkins Medicine/Oakstone Publishing Practical Reviews in Urology; Society of Urologic Oncology-Clinical Trials Consortium Board Of Directors; Society of Urologic


Oncology Young Urologic Oncologist. AA: Nothing to disclose. MSC: Grants or contracts: MDXHealth, Clinical Trial Agreement; Royalties or licenses: Springer Nature Group; Consulting fees:


Pfizer, Nonagen Bioscience Corp., Propella, Consulting JW, Myovant Sciences, Inc., TesoRx Pharma, LLC, Merck & Co., Inc.; Payment or honoraria for lectures, presentations, speakers


bureaus, manuscript writing or educational events: Remedica Medical Education & Publishing, MJH LifeSciences Prostate Cancer Roundtable, ASCO Symposium, Clinical Education Alliance,


BioPharm Communications, Abstract Reviewer, LynxDX; Payment for expert testimony: Walters, Stanley, Natrajan; Rhodes & Hieryonymus; Williams, Hall, Latherow; Moscarino & Treu;


Support for attending meetings and/or travel: American Urological Association (AUA), Society of Urologic Oncology, South Central Section of the AUA, UCSF Grand Rounds, Desai Sethi Urology


Institute, American Board of Urology, Onclive (USPROST8CON), American Society of Clinical Oncologists (ASCO), Astellas, Vanderbilt University, Thomas Jefferson University, VP, Southeastern


Section of the AUA, University of Wisconsin School of Medicine, VP; Participation on a Data Safety Monitoring Board or Advisory Board: Lantheus Advisory Board, Janssen Pharmaceuticals, Inc.


Advisory Board, Pacific Edge Diagnostics USA Ltd., Advisory Board, Janssen Biotech, Academic Urology Advisory Board, Signatera GU Cancers Advisory Board, Bayer Prostate Cancer Advisory


Council, Prokarium Ltd Bladder Cancer Advisory Board, Janssen Scientific Affairs, LLC Advisory Board, Bayer, Fallon Medica Advisory Board; Leadership or fiduciary role in other board,


society, committee or advocacy group, paid or unpaid: American Urological Association (AUA), South Central Section of the AUA, Society of Urological Oncology, Urology Times, American Board


of Urology. MDK: Nothing to disclose. CHM: Support for present the manuscript: NCI - P30 CA006973; Grants or contracts: V Foundation; Winn Career Development Award; Prostate Cancer


Foundation; Royalties or licenses: McGraw Hill; Consulting fees: Astellas Pharmaceuticals, Obseva, Bayer; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript


writing or educational events: Mashup MD; Participation on a Data Safety Monitoring Board or Advisory Board: Dendreon. AER: Grants or contracts: Site PI clinical trials with Bayer;


Consulting fees: Astellas/Pfizer, Bayer, Blue Earth, Janssen, Lantheus; Payment or honoraria for lectures, presentations, speakers bureaus: Astellas/Pfizer, Blue Earth, Janssen, Lantheus.


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this article is solely governed by the terms of such publishing agreement and applicable law. Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Shore, N.D., Antonarakis, E.S.,


Ross, A.E. _et al._ A multidisciplinary approach to address unmet needs in the management of patients with non-metastatic castration-resistant prostate cancer. _Prostate Cancer Prostatic


Dis_ 28, 250–259 (2025). https://doi.org/10.1038/s41391-024-00803-5 Download citation * Received: 04 October 2023 * Revised: 23 January 2024 * Accepted: 26 January 2024 * Published: 02 March


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