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

  • John Esther
  • Benjamin L. Maughan
  • Neysi Anderson
  • Neeraj AgarwalEmail author
  • Andrew W. HahnEmail author
Genitourinary Cancers (S Gupta, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Genitourinary Cancers

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.


nmCRPC MO CRPC SPARTAN PROSPER Enzalutamide Apalutamide Darolutamide 


Compliance With Ethical Standards

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.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA
  2. 2.GU Medical Oncology, Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA
  3. 3.Huntsman Cancer InstituteUniversity of Utah HospitalSalt Lake CityUSA

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