Overall Survival of Men with Metachronous Metastatic Hormone-sensitive Prostate Cancer Treated with Enzalutamide and Androgen Deprivation Therapy

Eur Urol. 2021 Sep;80(3):275-279. doi: 10.1016/j.eururo.2021.05.016. Epub 2021 May 22.


Men who initially present with localized prostate cancer and later develop metachronous metastases have a better prognosis than men with de novo metastatic disease and often have a low burden of disease on conventional imaging. Some have disease amenable to metastasis-directed therapy for lymph node or bone metastases, a strategy used by some because no documented overall survival (OS) benefit of combination systemic therapy in this setting. We report data for patients prospectively classified as "M0" at initial diagnosis from the interim analysis of the ENZAMET trial, with 34 mo of median follow-up for survivors. A total of 312 (28%) of the 1125 enrolled patients were classified as M0 at diagnosis, and 205 (66%) of the 312 patients had low-volume disease at study entry as per the CHAARTED criteria. The hazard ratio for OS, that is, HR(OS), was 0.56 (95% confidence interval [CI]: 0.29-1.06) with the addition of enzalutamide for all patients with metachronous metastatic hormone-sensitive prostate cancer, and for the low-volume subset the HR(OS) was 0.40 (95% CI: 0.16-0.97). The 3-yr OS was 83% without and 89% with enzalutamide for all patients with metachronous metastases, and 83% and 92%, respectively, for the low-volume subset. Intensification of hormonal therapy should strongly be considered for these men. PATIENT SUMMARY: Many men present with prostate cancer that has spread to distant sites beyond the prostate gland years after their initial diagnosis and treatment, while others have distant spread at the time the cancer is diagnosed. On average, men whose cancer comes back years after the initial diagnosis often survive much longer than men whose cancer has been found to spread to distant sites when it is first diagnosed. In this report, we demonstrate strong evidence for the first time that the survival of men whose cancer comes back years later is improved when drugs such as enzalutamide or apalutamide are added to testosterone suppression in this setting.

Keywords: Enzalutamide; Low volume; Metachronous; Metastatic hormone-sensitive prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists* / therapeutic use
  • Antineoplastic Agents* / therapeutic use
  • Benzamides* / therapeutic use
  • Clinical Trials as Topic
  • Humans
  • Male
  • Neoplasms, Second Primary* / drug therapy
  • Neoplasms, Second Primary* / mortality
  • Nitriles* / therapeutic use
  • Phenylthiohydantoin* / therapeutic use
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / mortality
  • Prostatic Neoplasms* / secondary
  • Prostatic Neoplasms, Castration-Resistant / drug therapy
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / secondary
  • Survival Analysis
  • Thiohydantoins* / therapeutic use


  • Androgen Antagonists
  • Antineoplastic Agents
  • Benzamides
  • Nitriles
  • Thiohydantoins
  • apalutamide
  • Phenylthiohydantoin
  • enzalutamide