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Is time to castration resistant prostate cancer a potential intermediate end-point for time to metastasis among men initiating androgen deprivation therapy for non-metastatic prostate cancer with rapid PSA doubling time (<9 months)?

Prostate Cancer and Prostatic Diseases volume 26, pages 151–155 (2023)Cite this article

Subjects

Abstract

Purpose

Metastasis-free survival (MFS) is a surrogate for overall survival (OS) in men with non-metastatic castration-resistant prostate cancer (CRPC), but this endpoint may take years to develop in men with non-metastatic castrate-sensitive disease. The study objective was to examine whether progression to CRPC is a potential intermediate endpoint for developing metastatic disease in patients with biochemical recurrence (BCR) after radical prostatectomy (RP).

Materials and methods

Men with BCR following RP who had PSA doubling times (PSADT) < 9 months and no metastasis at the time of initiating androgen deprivation therapy (ADT) (n = 210) were included. The primary objective was to assess the correlation between CRPC-free survival (CRPC-FS) and MFS, and the secondary objective was to assess the correlation between time to metastasis and time to CRPC. Kendall’s Tau was used to test the correlation for the primary and secondary outcomes.

Results

The median MFS was 104 months (95% CI: 83–114) and median CRPC-FS was 100 months (95% CI: 80–114). Based on the Kaplan–Meier curve, the greatest difference in time to MFS and CRPC-FS was around 70% free survival, which was reached at 61.2 months for MFS and 49.6 months for CRPC-FS. Kendall’s Tau for the correlation between CRPC-FS and MFS and between time to CRPC and time to metastasis was 0.867 (95% CI: 0.765–0.968) and 0.764 (95% CI: 0.644–0.884), respectively.

Conclusions

Given the high correlation between CRPC-FS and MFS, after validation, CRPC-FS may serve as a potential intermediate endpoint in trials for men with BCR initiating ADT following local therapy.

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Fig. 1: Consort diagram.
Fig. 2: Kaplan–Meier curves.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by funding from Pfizer. Furthermore, additional support included NIH R01CA231219 (WJA), and the Georgia Cancer Coalition (MKT). Views and opinions of, and endorsements by the author(s), do not reflect those of the US Army or the Dept. of Defense.

Author information

Authors and Affiliations

  1. Division of Urology, Department of Surgery, Medical College of Georgia – Augusta University, Augusta, GA, USA

    Zachary Klaassen & Martha K. Terris

  2. Georgia Cancer Center, Augusta, GA, USA

    Zachary Klaassen & Martha K. Terris

  3. Veterans Affairs Health Care System, Durham, NC, USA

    Lauren Howard, Jessica L. Janes, Amanda De Hoedt, Thomas J. Polascik & Stephen J. Freedland

  4. Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA

    Lauren Howard, Thomas J. Polascik & Yuan Wu

  5. Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA

    Christopher J. D. Wallis

  6. Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA

    William J. Aronson

  7. Department of Urology, UCLA School of Medicine, Los Angeles, CA, USA

    William J. Aronson

  8. Division of Urology, Oregon Health Sciences University, Portland, OR, USA

    Christopher J. Amling

  9. Urology Department, University of California San Diego Health System, San Diego, CA, USA

    Christopher J. Kane

  10. Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA

    Matthew R. Cooperberg

  11. Charlie Norwood Veterans Affairs Medical Center, Augusta, GA, USA

    Martha K. Terris

  12. Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Stephen J. Freedland

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  1. Zachary Klaassen
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Contributions

ZK: study concept and design, acquisition of data, analysis, and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, technical or material support. LEH: acquisition of data, analysis, and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, statistical analysis. CJDW: analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content. JL: acquisition of data, analysis, and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, statistical analysis. AH: study concept and design, acquisition of data, analysis, and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, technical or material support. WA: acquisition of data, analysis, and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, technical or material support. TJP: acquisition of data, analysis, and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, technical or material support. CA: acquisition of data, analysis, and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, technical or material support. CK: acquisition of data, analysis, and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, technical or material support. MC: acquisition of data, analysis, and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, technical or material support. MT: acquisition of data, analysis, and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, technical or material support. YW: acquisition of data, analysis, and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, statistical analysis. SF: study concept and design, acquisition of data, analysis, and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, technical or material support.

Corresponding author

Correspondence to Zachary Klaassen.

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Competing interests

ZK: Pfizer/Astellas, Bayer; SJF: Pfizer, Astellas, Janssen, Bayer, Astra Zeneca, Merck, Myovant, Clovis, Sanofi, Exact Sciences, Decipher Biosciences, Tempus, Exosome, Boston Scientific. The rest of the authors declare no competing interests.

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Klaassen, Z., Howard, L., Wallis, C.J.D. et al. Is time to castration resistant prostate cancer a potential intermediate end-point for time to metastasis among men initiating androgen deprivation therapy for non-metastatic prostate cancer with rapid PSA doubling time (<9 months)?. Prostate Cancer Prostatic Dis 26, 151–155 (2023). https://doi.org/10.1038/s41391-022-00585-8

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  • DOI: https://doi.org/10.1038/s41391-022-00585-8

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