Clinical considerations for the management of androgen indifferent prostate cancer.

TitleClinical considerations for the management of androgen indifferent prostate cancer.
Publication TypeJournal Article
Year of Publication2021
AuthorsBerchuck JE, Viscuse PV, Beltran H, Aparicio A
JournalProstate Cancer Prostatic Dis
Volume24
Issue3
Pagination623-637
Date Published2021 09
ISSN1476-5608
Abstract

BACKGROUND: Many systemic therapies for advanced prostate cancer work by disrupting androgen receptor signaling. Androgen indifferent prostate cancer (AIPC) variants, including aggressive variant prostate cancer (AVPC), neuroendocrine prostate cancer (NEPC), and double-negative prostate cancer (DNPC), are increasingly common and often overlapping resistance phenotypes following treatment with androgen receptor signaling inhibitors in men with metastatic castration-resistant prostate cancer and are associated with poor outcomes. Understanding the underlying biology and identifying effective therapies for AIPC is paramount for improving survival for men with prostate cancer.

METHODS: In this review, we summarize the current knowledge on AIPC variants, including our current understanding of the clinical, morphologic, and molecular features as well as current therapeutic approaches. We also explore emerging therapies and biomarkers aimed at improving outcomes for men with AIPC.

RESULTS AND CONCLUSIONS: Establishing consensus definitions, developing novel biomarkers for early and accurate detection, further characterization of molecular drivers of each phenotype, and developing effective therapies will be critical to improving outcomes for men with AIPC. Significant progress has been made toward defining the clinical and molecular characteristics of AVPC, NEPC, and DNPC. Novel diagnostic approaches, including cell-free DNA, circulating tumor cells, and molecular imaging are promising tools for detecting AIPC in clinical practice. Building on previous treatment advances, several clinical trials are underway evaluating novel therapeutic approaches in patients with AIPC informed by an understanding of variant-specific biology. In this review, we discuss how these recent and ongoing studies will help to improve diagnosis, prognosis, and therapy for men with AIPC.

DOI10.1038/s41391-021-00332-5
Alternate JournalProstate Cancer Prostatic Dis
PubMed ID33568748
PubMed Central IDPMC8353003
Grant ListP50 CA140388 / CA / NCI NIH HHS / United States
R37 CA241486 / CA / NCI NIH HHS / United States
U01 CA224044 / CA / NCI NIH HHS / United States
P50 CA211024 / CA / NCI NIH HHS / United States