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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

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

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

Abbreviations

mCRPC

Metastatic castration-resistant prostate cancer

MFS

Metastasis-free survival

nmCRPC

Non-metastatic castration-resistant prostate cancer

ALP

Alkaline phosphatase

ADT

Androgen deprivation therapy

OS

Overall survival

ARAT

Androgen receptor axis targeting

CT

Computed tomography

MRI

Magnetic resonance imaging

BS

Bone scintigraphy

MFS

Metastasis-free survival

PSADT

PSA doubling time

WBC

White blood cell

Hb

Hemoglobin

PLT

Platelet

LDH

Lactate dehydrogenase

CRP

C-reactive protein

HR

Hazard ratio

CI

Confidence interval

68 Ga-PSMA

68 Ga-labeled prostate-specific membrane antigen

PET

Positron emission tomography

Notes

Acknowledgements

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.

Funding

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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