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Impact of nadir PSA level and time to nadir during initial androgen deprivation therapy on prognosis in patients with metastatic castration-resistant prostate cancer

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Abstract

Purpose

We determine whether the nadir prostate-specific antigen level (PSA nadir) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) are prognostic factors in metastatic castration-resistant prostate cancer (mCRPC) patients.

Methods

We reviewed the Michinoku Japan Urological Cancer Study Group database, including 321 mCRPC patients. Optimal cutoff values for PSA nadir and TTN on survival were calculated with the receiver operating characteristic (ROC) curve. Patients were stratified into unfavorable (higher PSA nadir and/or shorter TTN) and favorable (lower PSA nadir and longer TTN) groups. The inversed probability of treatment weighing (IPTW)-adjusted Cox proportional hazard model was performed to evaluate the impact of the unfavorable group on overall survival (OS) after CRPC diagnosis.

Results

Median age and follow-up period were 71 years and 35 months, respectively. ROC curve analysis demonstrated cutoffs of PSA nadir > 0.64 ng/mL and TTN < 7 months. The unfavorable group included 248 patients who had significantly shorter OS after mCRPC. The IPTW-adjusted multivariate model revealed that the unfavorable group had a negative impact on OS in mCRPC patients [hazards ratio (HR) 2.98, P < 0.001].

Conclusions

Higher PSA nadir and shorter TTN during the initial ADT are poor prognostic factors in patients with mCRPC.

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Acknowledgments

We would like to thank Teppei Okamoto, Takuma Narita, Naoki Fujita, Hiromichi Iwamura, Yuki Fujita, Yukie Nishizawa, and the entire staff of the Department of Urology in Hirosaki University for their invaluable help with the data collection. The authors would also like to thank Enago (www.enago.jp) for the English language review.

Funding

This work was supported by a Grant-in-Aid for Scientific Research (Grant Nos. 15H02563, 15K15579, 17K11118, 17K11119, 17K16768, 17K16770, 17K16771, 18K16681, 18K16682, 18K16717, 18K16718, 18K16719, and 18K09157) from the Japan Society for the Promotion of Science.

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Authors and Affiliations

  1. Department of Urology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, 036-8562, Japan

    Itsuto Hamano, Shingo Hatakeyama & Chikara Ohyama

  2. Department of Urology, Akita University School of Medicine, 1-1-1, Hondo, Akita, 010-8543, Japan

    Shintaro Narita, Hiromi Sato & Tomonori Habuchi

  3. Department of Urology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan

    Masahiro Takahashi, Koji Mitsuzuka & Yoichi Arai

  4. Department of Urology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, Yamagata, 990-9585, Japan

    Toshihiko Sakurai & Norihiko Tsuchiya

  5. Department of Urology, Miyagi Cancer Center, 47-1, Nodayama, Shiote, Aijima, Natori, Miyagi, 981-1293, Japan

    Sadafumi Kawamura & Tatsuo Tochigi

  6. Department of Urology, Yamagata Prefectural Central Hospital, 1800, Aoyanagi, Yamagata, 990-2292, Japan

    Senji Hoshi

  7. Department of Urology, Iwate Prefectural Isawa Hospital, 61, Ryugababa, Mizusawa, Oshu, Iwate, 023-0864, Japan

    Masanori Ishida & Jiro Shimoda

  8. Department of Urology, Aomori Prefectural Central Hospital, 2-1-1, Higashi-tsukurimichi, Aomori, Aomori, 030-8553, Japan

    Toshiaki Kawaguchi

  9. Department of Urology, Sendai City Hospital, 1-1-1, Nagamachi, Asuto, Taihaku-ku, Sendai, Miyagi, 982-8502, Japan

    Shigeto Ishidoya

Authors
  1. Itsuto Hamano
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  2. Shingo Hatakeyama
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  3. Shintaro Narita
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  15. Norihiko Tsuchiya
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  16. Yoichi Arai
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  17. Tomonori Habuchi
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  18. Chikara Ohyama
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Contributions

IH: manuscript writing, data analysis. SH: manuscript editing, data analysis. SN, MT, TS, SK, SH, MI, TK, SI, JS, HS, KM, and TT: project development, data collection. NT, YA, TH, and CO: project development, critical review and supervision

Corresponding author

Correspondence to Shingo Hatakeyama.

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Hamano, I., Hatakeyama, S., Narita, S. et al. Impact of nadir PSA level and time to nadir during initial androgen deprivation therapy on prognosis in patients with metastatic castration-resistant prostate cancer. World J Urol 37, 2365–2373 (2019). https://doi.org/10.1007/s00345-019-02664-3

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