Management of Nonmetastatic Castration-Resistant Prostate Cancer: Recent Advances and Future Direction

Opinion statement

Nonmetastatic castration-resistant prostate cancer (nmCRPC) comprises a relatively narrow niche of advanced prostate cancer, but the treatment landscape for men with nmCRPC has drastically changed over the past year. Prior to the SPARTAN and PROSPER trials, men with nmCRPC were commonly treated with first-generation androgen receptor antagonists, such as bicalutamide or flutamide, or with estrogens or ketoconazole, none of which were associated with any proven survival benefit. The SPARTAN trial evaluated apalutamide versus placebo for men with nmCRPC and found that apalutamide significantly improved metastasis-free survival (MFS), the primary endpoint of this trial. Similarly, the PROSPER trial showed that enzalutamide significantly improved MFS compared with placebo for men with nmCRPC. In both trials, the data for overall survival was immature at the time of analysis. The SPARTAN and PROSPER trials led to the approval of apalutamide and enzalutamide, respectively, for men with nmCRPC. More recently, the phase 3 trial ARAMIS showed that darolutamide, a novel androgen receptor antagonist, also improves MFS compared with placebo for men with nmCRPC, and this trial is expected to garner regulatory approval for darolutamide in the nmCRPC setting. Novel imaging modalities are becoming more prevalent for the diagnostic evaluation of men with prostate cancer and are more sensitive than conventional bone or CT scans for detection of oligometastatic disease that previously was undetected. These modalities are likely to reduce the incidence and prevalence of nmCRPC in the near future. Ultimately, the treatment options for men with nmCRPC have significantly improved over the past 2 years.

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Corresponding authors

Correspondence to Neeraj Agarwal MD or Andrew W. Hahn MD.

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Conflict of Interest

John Esther declares that he has no conflict of interest.

Benjamin L. Maughan has received compensation from Janssen Oncology, Exelixis, Peloton Therapeutics, and Tempus for participation on advisory boards.

Neysi Anderson declares that she has no conflict of interest.

Neeraj Agarwal has received research funding (paid to his institution) from Active Biotech, AstraZeneca, Bavarian Nordic, Bristol-Myers Squibb, Calithera, Celldex, Eisai, Exelixis, Genentech, GlaxoSmithKline, Immunomedics, Janssen, Medivation, Merck, NewLink Genetics, Novartis, Pfizer, Prometheus, Rexahn, Sanofi, Takeda, and TRACON Pharmaceuticals; and has received compensation from Pfizer, Novartis, Merck, Genentech, Eisai, Exelixis, Clovis, EMD Serono, Bristol-Myers Squibb, AstraZeneca, FoundationOne, Astellas, Eli Lilly, Bayer, Argos, Medivation, and Nektar for service as a consultant.

Andrew W. Hahn declares that he has no conflict of interest.

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Esther, J., Maughan, B.L., Anderson, N. et al. Management of Nonmetastatic Castration-Resistant Prostate Cancer: Recent Advances and Future Direction. Curr. Treat. Options in Oncol. 20, 14 (2019).

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  • nmCRPC
  • Enzalutamide
  • Apalutamide
  • Darolutamide