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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Change history
20 April 2024
A Correction to this paper has been published: https://doi.org/10.1038/s41391-024-00835-x
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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.
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This activity is supported by an independent medical education grant from Bayer for medical writing of this manuscript.
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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.
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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. 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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. 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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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DOI: https://doi.org/10.1038/s41391-024-00803-5
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