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Sequencing Treatment for Castration-Resistant Prostate Cancer

  • Genitourinary Cancers (W Oh and M Galsky, Section Editors)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Prostate cancer is the most common non-cutaneous cancer diagnosed in men and the second leading cause of male cancer deaths in the USA. While most cases are diagnosed in early stages, some will present as or progress to metastatic disease and eventually castration-resistant prostate cancer (mCRPC) which has a mortality rate exceeding 50 %. There are currently six approved systemic life-prolonging therapies for use in mCRPC, yet little data to guide sequencing. Clinical factors, including the presence or absence of symptoms and the presence or absence of visceral metastases, should help determine the best therapeutic choice at each treatment node. Those with asymptomatic bone-only disease could be considered for sipuleucel-T, abiraterone, enzalutamide, or docetaxel in the first-line setting. For symptomatic disease, docetaxel could be used or radium-223 if disease is only present in the bone. In the second-line setting, sipuleucel-T or radium-223 can be used in the appropriate clinical setting. Taxane chemotherapy could be used if a novel androgen-directed therapy was used in the first-line setting. Cabazitaxel, if docetaxel was previously used, should be considered. There is scarce data on best treatment options in the third-line setting. In general, we recommend alternating between androgen-targeting agents and taxane chemotherapy. Finally, consideration should be given to testing for the androgen receptor splice variant AR-V7, which may be a relevant treatment-specific biomarker to aid in the selection of androgen-targeting therapy versus chemotherapy at each treatment juncture. Mutation testing for DNA damage repair defects can also be considered, as such patients may benefit from investigational poly ADP ribose polymerase (PARP) inhibitors or platinum-based chemotherapies. Several ongoing studies have been designed to answer some of these sequencing questions, including the biomarker questions, and will hopefully continue to inform us about rational therapy selection in mCRPC.

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Acknowledgments

CEH has no funding sources to report. ESA has received funding from the Prostate Cancer Foundation, the Patrick C Walsh Fund, and the NIH grants R01 CA185297 and P30 CA006973.

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  1. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 600 N. Wolfe Street, Harvey 306, Baltimore, MD, 21287, USA

    Catherine E. Handy M.D., M.P.H.

  2. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, 1650 Orleans Street, CRB1 - Room 1M45, Baltimore, MD, 21287, USA

    Emmanuel S. Antonarakis M.D.

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Catherine E. Handy declares that she has no conflict of interest.

Emmanuel S. Antonarakis has served as a paid consultant/advisor for Janssen, Astellas, Sanofi, Dendreon, Essa, and Medivation; has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Exelixis, Genentech, Novartis, and Tokai; and is a co-inventor of a technology that has been licensed to Tokai.

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Handy, C.E., Antonarakis, E.S. Sequencing Treatment for Castration-Resistant Prostate Cancer. Curr. Treat. Options in Oncol. 17, 64 (2016). https://doi.org/10.1007/s11864-016-0438-9

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