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

Prostate Cancer and Prostatic Diseases (2024)Cite this article

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A Correction to this article was published on 20 April 2024

This article has been updated

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.

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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

  1. GenesisCare US, Myrtle Beach, SC, USA

    Neal D. Shore

  2. University of Minnesota Masonic Cancer Center, Minneapolis, MN, USA

    Emmanuel S. Antonarakis

  3. Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Ashley E. Ross

  4. Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Catherine H. Marshall

  5. University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Kelly L. Stratton, Adanma Ayanambakkam & Michael S. Cookson

  6. University of California, San Diego, La Jolla, CA, USA

    Rana R. McKay

  7. Mayo Clinic, Phoenix, AZ, USA

    Alan H. Bryce

  8. Dana Farber Cancer Institute, Boston, MA, USA

    Marina D. Kaymakcalan

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  1. Neal D. Shore
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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.

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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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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 (2024). https://doi.org/10.1038/s41391-024-00803-5

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