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

  • Keiichiro MoriEmail author
  • Takahiro Kimura
  • Wataru Fukuokaya
  • Kosuke Iwatani
  • Keigo Sakanaka
  • Gaku Kurokawa
  • Takafumi Yanagisawa
  • Hiroshi Sasaki
  • Jun Miki
  • Tatsuya Shimomura
  • Kenta Miki
  • Takashi Hatano
  • Katsuhisa Endo
  • Shin Egawa
Original Article



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.


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.


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).


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.


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



Metastatic castration-resistant prostate cancer


Metastasis-free survival


Non-metastatic castration-resistant prostate cancer


Alkaline phosphatase


Androgen deprivation therapy


Overall survival


Androgen receptor axis targeting


Computed tomography


Magnetic resonance imaging


Bone scintigraphy


Metastasis-free survival


PSA doubling time


White blood cell






Lactate dehydrogenase


C-reactive protein


Hazard ratio


Confidence interval

68 Ga-PSMA

68 Ga-labeled prostate-specific membrane antigen


Positron emission tomography



The authors thank Prof. Shin Egawa and Dr. Takahiro Kimura at Jikei University School of Medicine for their valuable comments and cooperations.

Author contributions

KM: project development, data collection, data analysis, manuscript writing/editing; TK: project development, data analysis, manuscript writing/editing; WF: data collection; KI: data collection KS: data collection; GK: data collection; TY: project development; HS: project development; JM: project development; TS: project development; KM: project development; TH: project development; KE: project development; SE: project development, manuscript writing/editing.


No founding sources were obtained for this study.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Statement of human rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Jikei University School of Medicine (30-416(9437)) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.


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Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  • Keiichiro Mori
    • 1
    Email author
  • Takahiro Kimura
    • 1
  • Wataru Fukuokaya
    • 1
  • Kosuke Iwatani
    • 1
  • Keigo Sakanaka
    • 1
  • Gaku Kurokawa
    • 1
  • Takafumi Yanagisawa
    • 1
  • Hiroshi Sasaki
    • 1
  • Jun Miki
    • 1
  • Tatsuya Shimomura
    • 1
  • Kenta Miki
    • 1
  • Takashi Hatano
    • 1
    • 2
  • Katsuhisa Endo
    • 1
    • 2
  • Shin Egawa
    • 1
  1. 1.Department of UrologyJikei University School of MedicineTokyoJapan
  2. 2.Department of UrologyJR Tokyo General HospitalTokyoJapan

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