Update on systemic prostate cancer therapies: management of metastatic castration-resistant prostate cancer in the era of precision oncology

Nuhn, Philipp; De Bono, Johann S.; Fizazi, Karim; Freedland, Stephen J.; Grilli, Maurizio; Kantoff, Philip W.; Sonpavde, Guru; Sternberg, Cora N.; Yegnasubramanian, Srinivasan; Antonarakis, Emmanuel S.

doi:10.1016/j.eururo.2018.03.028

Cited by 437Prostate Cancer Treatment and ResearchProstate Cancer Diagnosis and TreatmentBone health and treatments

Update on systemic prostate cancer therapies: management of metastatic castration-resistant prostate cancer in the era of precision oncology

Nuhn, Philipp, De Bono, Johann S., Fizazi, Karim, Freedland, Stephen J., Grilli, Maurizio, Kantoff, Philip W., Sonpavde, Guru, Sternberg, Cora N. +2 more·2019·European Urology

DOI 10.1016/j.eururo.2018.03.028

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Abstract

Context Introduction of novel agents for the management of advanced prostate cancer provides a range of treatment options with notable benefits for men with metastatic castration-resistant prostate cancer (mCRPC). At the same time, understanding of optimal patient selection, effective sequential use, and development of resistance patterns remains incomplete.Objective To review current systemic therapies and recent advances in drug development for mCRPC and strategies to aid in patient selection and optimal sequencing.Evidence acquisition A literature review of PubMed/Medline, Cochrane Library, Current Contents Medicine, Web of Science, Clinical Trial.Gov, WHO-ICTRP (January 2004-November 2017), and the proceedings of major international meetings (2015/2016/2017) was performed in November 2017.Evidence synthesis In the last few years, several new options for treatment of mCRPC have shown a survival benefit in phase III trials besides docetaxel:abiraterone, enzalutamide, cabazitaxel, radium-223, and sipuleucel-T. Radium-223 and denosumab have increased options in management of bone metastases. Currently, novel agents such as next-generation androgen receptor (AR) axis-targeting treatments, immunotherapeutics, or therapies targeting other oncogenic and genomic pathways, particularly poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors and PD-1 inhibitors, are under clinical investigation. With increasing treatment options for mCRPC, information on how to personalize management and how to select and sequence existing therapies is beginning to emerge, as are predictive biomarkers (homologous repair mutations, mismatch repair mutations, AR splice variant 7). Finally, early use of active agents in the castration-sensitive state will likely also change the clinical management of the disease when it becomes castrate resistant.Conclusions The emergence of new drugs for mCRPC has improved treatment options dramatically. Currently, systemic treatment options for mCRPC include hormonal therapy, chemotherapy, immunotherapy, and radionuclide therapy as well as bone-modifying agents and palliative or supportive measures. Further, new genetically targeted agents (PARP inhibitors and PD-1 inhibitors) are on the horizon for certain subsets of biomarker-selected patients. The best strategies for patient selection and optimal sequential use to achieve the longest cumulative survival improvement and to prevent early resistance remain unclear.Patient summary The current literature and proceedings from relevant congresses related to available systemic agents for the treatment of metastatic castration-resistant prostate cancer, including novel genetically targeted therapies, including poly(adenosine diphosphate-ribose) polymerase inhibitors and PD-1 inhibitors, were reviewed. Current therapies and ongoing developments are discussed.

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Authors: Nuhn, P., De Bono, J. S., Fizazi, K., Freedland, S. J., Grilli, M., Kantoff, P. W., Sonpavde, G., Sternberg, C. N., Yegnasubramanian, S., & Antonarakis, E. S.
Affiliations: Heidelberg University (DE)
Université Paris-Sud (FR)
Cedars-Sinai Medical Center (US)
Memorial Sloan Kettering Cancer Center (US)
Dana-Farber Cancer Institute (US)
Azienda Ospedaliera San Camillo-Forlanini (IT)
Johns Hopkins University (US)
Corresponding author: Antonarakis, Emmanuel S.
ORCID: Fizazi, Karim
Freedland, Stephen J.
Grilli, Maurizio
Kantoff, Philip W.
Sonpavde, Guru
Sternberg, Cora N.
Yegnasubramanian, Srinivasan
Antonarakis, Emmanuel S.
Venue: European Urology
Publisher: Elsevier BV
Published: 2019-01
Volume: 75
Issue: 1
Pages: 88-99
ISSN: 0302-2838 (ISSN-L)
DOI: 10.1016/j.eururo.2018.03.028
OpenAlex: W2800410357
Cited by: 437
References: 100
Citations by year: 2026: 19 · 2025: 33 · 2024: 46 · 2023: 45 · 2022: 63 · 2021: 81 · 2020: 77 · 2019: 54 · 2018: 16 · 2014: 1
FWCI: 10.12
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: European Urology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Diagnosis and Treatment
Health Sciences › Medicine › Oncology › Bone health and treatments
Keywords: metastatic castration-resistant prostate cancer, systemic therapy, precision oncology, treatment sequencing, predictive biomarkers, PARP inhibitors, PD-1 inhibitors, abiraterone, enzalutamide, cabazitaxel, radium-223, sipuleucel-T, denosumab, bone metastasis, immunotherapy, drug resistance
MeSH terms: Androgen Antagonists, Antineoplastic Agents, Humans, Male, Patient Selection, Precision Medicine, Prostatic Neoplasms, Castration-Resistant

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Update on systemic prostate cancer therapies: management of metastatic castration-resistant prostate cancer in the era of precision oncology

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