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Prognostic significance of total plasma cell-free DNA level and androgen receptor amplification in castration-resistant prostate cancer

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Abstract

Purpose

To investigate the prognostic significance of total cell-free DNA (cfDNA) level and androgen receptor amplification (AR-amp) in patients with castration-resistant prostate cancer (CRPC).

Methods

We retrospectively compared the total cfDNA level and AR-amp in 42 individuals without prostate cancer, 57 patients with localized prostate cancer without androgen-deprivation therapy (ADT), 97 patients with castration-sensitive prostate cancer (CSPC) with ADT, and 97 patients with CRPC. The association of these cfDNA biomarkers on disease status and overall survival was evaluated using Kaplan–Meier analysis and multivariable Cox regression analysis. Finally, a simple risk model was developed including total cfDNA and AR-amp to predict poor prognosis.

Results

The median total cfDNA level and AR-amp in patients with CRPC was 387 pg/μL and 1.07 copies, respectively. The total cfDNA levels and AR-amp were significantly higher in the patients with CRPC than in individuals without prostate cancer, patients with localized prostate cancer without ADT, and patients with CSPC with ADT. Total cfDNA-high (> 600 pg/μL) and AR-amp-high (> 1.26 copies) were significantly associated with poor overall survival. Multivariable Cox regression analysis showed cfDNA-high and AR-amp-high were significantly associated with poor overall survival in patients with CRPC. We developed a risk model using cfDNA-high (score 1) and AR-amp-high (score 1). The risk score 1–2 was significantly associated with worse overall survival than score 0.

Conclusion

Total cfDNA level and AR-amp are potential biomarkers for poor prognosis in patients with CRPC.

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Acknowledgements

The authors would like to thank Yuki Fujita, Yukie Nishizawa, and Satomi Sakamoto for their invaluable support. The authors would also like to thank Enago (www.enago.jp) for the English language review.

Funding

This work was supported by Japan Society for the Promotion of Science (JSPS), Grant Numbers: 18K09157 (T.Y.), 19H05556 (C.O.), 20K09517 (S.H.), 20K18106 (Y.K.), and 20K18107 (I.H.).

Author information

Authors and Affiliations

  1. Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    Yuka Kubota, Itsuto Hamano, Sakae Konishi, Teppei Okamoto, Hayato Yamamoto, Yasuhiro Hashimoto & Chikara Ohyama

  2. Department of Advanced Blood Purification Therapy, Hirosaki University Graduate School of Medicine, 5 Zaifu-chou, Hirosaki, 036-8562, Japan

    Shingo Hatakeyama & Chikara Ohyama

  3. Department of Glycotechnology, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    Tohru Yoneyama

  4. Department of Cancer Immunology and Cell Biology, Oyokyo Kidney Research Institute, Hirosaki, Japan

    Mihoko Sutoh Yoneyama

  5. Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

    Takahiro Yoneyama & Chikara Ohyama

Authors
  1. Yuka Kubota
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  2. Shingo Hatakeyama
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Contributions

Project development: SH, TY, CO. Manuscript writing: YK, SH, TY. Data analysis: SH, TY. Data collection: MSY, IH, SK, TO, HY, TY, YH. Critical review: CO.

Corresponding author

Correspondence to Shingo Hatakeyama.

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Conflict of interest

None of the authors have any conflicts of interest to declare.

Ethics statement

The present retrospective, multicenter study was performed in accordance with the ethical standards of the Declaration of Helsinki, and it was approved by the ethics review board of the Hirosaki University School of Medicine (authorization number: 2018–062) and all hospitals. Pursuant to the provisions of the ethics committee and the ethics guidelines in Japan, written informed consent is not required for public disclosure of study information in the case of a retrospective and/or observational study using materials, such as existing documents (opt-out approach).

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Supplementary Information

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345_2021_3649_MOESM1_ESM.pdf

Supplementary file1 The total cfDNA and AR-amp were compared between the pre-docetaxel and post docetaxel status (A). The median time from CRPC diagnosis to cfDNA evaluation was 12 months. The relationship between the time from CRPC diagnosis and cfDNA parameters was evaluated (B). There were no significant differences in the total cfDNA level and AR-amp between <12 and ≥12 months. The optimal cutoff value of total cfDNA (C) and AR-amp (D) for any cause of death were defined using a ROC curve and the AUC. (PDF 200 KB)

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Kubota, Y., Hatakeyama, S., Yoneyama, T. et al. Prognostic significance of total plasma cell-free DNA level and androgen receptor amplification in castration-resistant prostate cancer. World J Urol 39, 3265–3271 (2021). https://doi.org/10.1007/s00345-021-03649-x

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  • DOI: https://doi.org/10.1007/s00345-021-03649-x

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