Androgen receptor signaling-targeted therapy and taxane chemotherapy induce visceral metastasis in castration-resistant prostate cancer

Prostate. 2021 Jan;81(1):72-80. doi: 10.1002/pros.24082. Epub 2020 Oct 13.

Abstract

Background: Visceral metastasis (VM), an important poor prognostic factor of prostate cancer (PC), is not commonly observed in castration sensitive status but is often observed after castration-resistant progression. However, the site, timing of emergence, and incidence of VM in castration-resistant patients have not yet been fully elucidated.

Methods: Demographic, surgical, pathological, and follow-up data of PC patients treated at Kanazawa University Hospital between January 2000 and December 2016 were retrospectively analyzed using their medical charts. From this data, risk factors of VM and survival of patients with VM were elucidated.

Results: Of 1364 patients, 21 (1.5%) had VM at diagnosis. Of 179 (13.1%) castration-resistant patients, 55 experienced emergence of new VM during treatment course. Incidence of new VM, especially nonlung, such as liver and adrenal metastases, increased significantly in proportion with the number of prescribed treatments. Multivariate analysis revealed that T stage, M stage, age, and treatment history with androgen receptor (AR) signaling-targeted agents and/or taxanes significantly increased the risk of VM. Compared with the group with VM at diagnosis, survival after diagnosis of VM following treatment was significantly shorter.

Conclusion: Although sequential use of new AR signaling-targeted agents and taxanes for castration-resistant PC (CRPC) is a standard treatment strategy, it often results in development of VM. Elucidating the mechanisms of VM are essential to improve survival in patients with CRPC.

Keywords: androgen receptor; castration-resistance; prostate cancer; taxane; visceral metastasis.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androstenes / therapeutic use
  • Docetaxel / therapeutic use
  • Humans
  • Incidence
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Phenylthiohydantoin / analogs & derivatives
  • Phenylthiohydantoin / therapeutic use
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / epidemiology
  • Prostatic Neoplasms, Castration-Resistant / metabolism*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Receptors, Androgen / metabolism*
  • Retrospective Studies
  • Risk Factors
  • Signal Transduction / drug effects
  • Taxoids / therapeutic use

Substances

  • AR protein, human
  • Androstenes
  • Receptors, Androgen
  • Taxoids
  • Docetaxel
  • Phenylthiohydantoin
  • cabazitaxel
  • enzalutamide
  • abiraterone