International Urology and Nephrology

, Volume 52, Issue 1, pp 77–85 | Cite as

Predictors of poor response to first-generation anti-androgens as criteria for alternate treatments for patients with non-metastatic castration-resistant prostate cancer

  • Kenichiro Fukuoka
  • Jun TeishimaEmail author
  • Hirotaka Nagamatsu
  • Shogo Inoue
  • Tetsutaro Hayashi
  • Koji Mita
  • Masanobu Shigeta
  • Kanao Kobayashi
  • Mitsuru Kajiwara
  • Yuichi Kadonishi
  • Takatoshi Tacho
  • Akio Matsubara
Urology - Original Paper



There are no criteria for administering first- or second-generation anti-androgens (FGA and SGA, respectively) to patients with non-metastatic castration-resistant prostate cancer (nmCRPC). This study aimed to assess the efficacy of alternative FGA therapy in nmCRPC patients and the prognosis of these patients and to identify factors for predicting patients potentially responsive to FGA.


Data from 63 men with nmCRPC who underwent alternative FGA therapy (bicalutamide, flutamide, or chlormadinone acetate) as first-line therapy after failure of primary androgen-deprivation therapy (PADT) between 2004 and 2017 at Hiroshima University Hospital and affiliated hospitals were retrospectively investigated. The associations of clinicopathological parameters with overall survival (OS) and prostate-specific antigen (PSA) progression-free survival (PFS) of alternative FGA-treated patients were analyzed.


Time to CRPC [p = 0.007, hazard ratio (HR) = 4.77], regional lymph node involvement at the diagnosis of CRPC (p = 0.022, HR = 2.42), and PSA-PFS of alternative FGA therapy ≤ 6 months (p = 0.020, HR = 2.39) were identified as prognostic factors using a multivariate analysis. Additionally, Cox proportional hazard models revealed that PSA nadir value > 1 ng/mL during PADT (p = 0.034, HR = 2.40) and time from starting PADT to PSA nadir ≤ 1 year (p = 0.047, HR = 1.85) were predictive factors for worse PSA-PFS in alternative FGA therapy.


Shorter time to CRPC, regional lymph node involvement, PSA nadir during PADT > 1 ng/mL, and time from starting PADT to PSA nadir ≤ 1 year might suggest the potential benefit of immediate commencement of SGA, compared to FGA administration after nmCRPC diagnosis.


Non-metastatic castration-resistant prostate cancer Prognostic factors PSA nadir Time to nadir Alternative first-generation anti-androgen therapy 



We are grateful to R. Kanaoka, Y. Kohada, T. Babasaki, S. Ohara, and H. Iwamoto for their assistance with data collection. We would like to thank Editage ( for English language editing.


This study was not funded by a grant.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All the procedures performed in the study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments. For this type of study, formal consent is not required.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Kenichiro Fukuoka
    • 1
    • 2
  • Jun Teishima
    • 1
    Email author
  • Hirotaka Nagamatsu
    • 2
  • Shogo Inoue
    • 1
  • Tetsutaro Hayashi
    • 1
  • Koji Mita
    • 3
  • Masanobu Shigeta
    • 4
  • Kanao Kobayashi
    • 5
  • Mitsuru Kajiwara
    • 6
  • Yuichi Kadonishi
    • 7
  • Takatoshi Tacho
    • 8
  • Akio Matsubara
    • 1
  1. 1.Department of Urology, Graduate School of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Department of UrologyNakatsu Daiichi HospitalNakatsuJapan
  3. 3.Department of UrologyHiroshima City Asa Citizens HospitalHiroshimaJapan
  4. 4.Department of UrologyNational Hospital Organization Kure Medical Center and Chugoku Cancer CenterKureJapan
  5. 5.Department of UrologyChugoku Rosai HospitalKureJapan
  6. 6.Department of UrologyHiroshima Prefectural HospitalHiroshimaJapan
  7. 7.Department of UrologyJA Onomichi General HospitalOnomichiJapan
  8. 8.Department of UrologyMatsuyama Red Cross HospitalMatsuyamaJapan

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