Treatment of Advanced Prostate Cancer

Abstract

The therapeutic landscape of prostate cancer has been transformed over the last decade by new therapeutics, advanced functional imaging, next-generation sequencing, and better use of existing therapies in early-stage disease. Until 2004, progression on androgen deprivation therapy for metastatic disease was treated with the addition of secondary hormonal manipulation; in the last decade, six systemic agents have been approved for the treatment of castration-resistant prostate cancer. We review clinical trials and survival benefit for these therapies and assess how the understanding of the disease shifted as these therapies were developed. We also discuss advances in noncastrate disease states, identification of biomarkers for prognosis and treatment selection, and opportunities in locoregional therapy to delay androgen deprivation therapy.

Keywords: CRPC; castration-resistant prostate cancer; dynamic classification; mHSPC; metastatic hormone-sensitive prostate cancer; systemic therapy.

Figure 1

Model of prostate cancer clinical states proposed by Prostate Cancer Working Group 3 (3), with management options in different clinical states. Abbreviations: ADT, androgen deprivation therapy; mCRPC, metastatic castration-resistant prostate cancer; nmCRPC, nonmetastatic castration-resistant prostate cancer; PSA, prostate-specific antigen. *Positive phase III data available but not approved by the US Food and Drug Administration (FDA). **Received FDA breakthrough designation based on phase II TOPARP-A trial. ***FDA approval based on tissue-agnostic microsatellite instability.