Values of alkaline phosphatase at the diagnosis of castration resistance and response to primary androgen deprivation therapy as predictors of subsequent metastasis in non-metastatic castration-resistant prostate cancer

Int J Clin Oncol. 2020 Mar;25(3):479-485. doi: 10.1007/s10147-019-01541-8. Epub 2019 Sep 11.

Abstract

Purpose: Among various therapeutic options available for metastatic castration-resistant prostate cancer (mCRPC), only apalutamide and enzalutamide have shown evidences of improved metastasis-free survival (MFS) for non-metastatic castration-resistant prostate cancer (nmCRPC). However, there is a paucity of evidence to indicate who may be targeted for aggressive therapy among patients with nmCRPC. The objectives of this retrospective study were to explore predictors of metastasis in patients with nmCRPC and to identify a subpopulation of patients with nmCRPC who may benefit from aggressive therapy.

Methods: A total of 115 patients with CRPC who had no metastasis detected at the time of diagnosis of CRPC were included in this retrospective study. All patients were treated at Jikei University and its affiliated hospitals. The primary outcome measure was MFS from the time of diagnosis of CRPC. Predictors of MFS were also explored with a multivariate Cox hazard model.

Results: The median observation period after diagnosis of CRPC was 30 months (range 2-143 months). Kaplan-Meier analysis revealed a median MFS of 76. Multivariate analysis demonstrated that low alkaline phosphatase (ALP) values at diagnosis of CRPC and favorable response to primary androgen deprivation therapy (ADT) were significant predictors of longer MFS (P = 0.011, and 0.031, respectively).

Conclusions: Results of this study suggest that high ALP values at diagnosis of CRPC and poor response to primary ADT may predict the propensity of metastasis in patients with nmCRPC. Further prospective studies will be required enrolling more patients to confirm our findings.

Keywords: Alkaline phosphatase (ALP); Castration-resistant prostate cancer (nmCRPC); Metastasis-free survival (MFS); Non-metastatic; Retrospective study.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alkaline Phosphatase / blood*
  • Androgen Antagonists / therapeutic use
  • Benzamides
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nitriles
  • Phenylthiohydantoin / analogs & derivatives
  • Phenylthiohydantoin / therapeutic use
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / pathology*
  • Retrospective Studies
  • Thiohydantoins / therapeutic use
  • Treatment Outcome

Substances

  • Androgen Antagonists
  • Benzamides
  • Nitriles
  • Thiohydantoins
  • apalutamide
  • Phenylthiohydantoin
  • enzalutamide
  • Alkaline Phosphatase