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Early PSA decline after starting second-generation hormone therapy in the post-docetaxel setting predicts cancer-specific survival in metastatic castrate-resistant prostate cancer

Prostate Cancer and Prostatic Diseases (2023)Cite this article

Subjects

Abstract

Background

The objective of this study was to evaluate the prognostic value of early PSA decline following initiation of second-generation hormone therapy (2nd HT), namely abiraterone acetate or enzalutamide, in patients with taxane-refractory metastatic castrate-resistant prostate cancer (mCRPC) and evaluate utility of this metric in informing intensified surveillance/imaging protocols.

Methods

We retrospectively identified 75 mCRPC patients treated with 2nd HT following docetaxel failure (defined as PSA rise and radiographic progression). Patients were categorized patients into two cohorts based on the first PSA within 3 months after initiation of therapy: PSA reduction ≥50% (Group A) and PSA reduction <50% (Group B). The primary endpoint was cancer-specific mortality (CSM). The secondary endpoint was radiographic disease progression (rDP) on 2nd HT. In univariate and multivariate analyses, we investigated factors associated with rPD and CSM.

Results

We included 75 patients (52 in Group A, 23 in Group B) in the analytic cohort. Baseline clinico-demographic characteristics, including median age, primary Gleason score risk group, median pre-treatment PSA, disease burden, site of metastases, and pre-treatment ECOG score were not statistically different between the two groups. Median follow up time was 30 months and the median time to radiographic disease progression was 28.1 and 12.5 months (p = 0.002) in cohorts A and B, respectively. On univariate and multivariate analyses, both PSA reduction ≥50% and volume of metastatic disease were significantly associated with a decreased risk of radiographic disease progression (HR 0.41, 95% CI 0.21–0.80, p = 0.0113) as well as a decreased risk of cancer-specific mortality (HR 0.29, 95% CI 0.09–0.87, p = 0.0325).

Conclusion

PSA reduction ≥50% within 3 months of starting 2nd HT was associated with significantly improved radiographic disease progression-free survival and 3-year cancer-specific mortality. This suggests using PSA 50%-decline metric in surveillance patients with on 2nd HT and identifies patients who require further evaluation with imaging.

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Data availability

The authors affirm that the data substantiating the conclusions of this study can be found within the article itself, including its figures and tables. In addition, the raw data underpinning the study’s results is accessible from the corresponding author in an anonymized format upon reasonable request for the purpose of review.

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Author notes

  1. These authors contributed equally: Daniel S. Childs, Jack R. Andrews.

Authors and Affiliations

  1. Department of Urology, Mayo Clinic, Rochester, MN, USA

    Mohamed E. Ahmed, Matthew S. Lee, Ahmed M. Mahmoud, Ajay Gopalakrishna, Raevti Bole, Rimki Haloi, Robert Jeffrey Karnes & Eugene D. Kwon

  2. Villanova University Charles Widger School of Law, Villanova, PA, USA

    Vidhu B. Joshi

  3. Department of Radiology, Division of Nuclear Medicine, Mayo Clinic, Rochester, MN, USA

    A. Tuba Kendi & Michael S. Bold

  4. Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, AZ, USA

    Alan H. Bryce

  5. Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA

    Daniel S. Childs

  6. Department of Urology, Mayo Clinic, Scottsdale, AZ, USA

    Jack R. Andrews

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  1. Mohamed E. Ahmed
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Contributions

Conceptualization, MEA; writing—original draft preparation, MEA, and MSL; writing—review and editing, AMM, AG, RB, ATK, DSC, and MSB; data collection: RH; statistical analysis: MEA; supervision, AHB, RJK, EDK, and JRA. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Mohamed E. Ahmed.

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Ahmed, M.E., Lee, M.S., Mahmoud, A.M. et al. Early PSA decline after starting second-generation hormone therapy in the post-docetaxel setting predicts cancer-specific survival in metastatic castrate-resistant prostate cancer. Prostate Cancer Prostatic Dis (2023). https://doi.org/10.1038/s41391-023-00751-6

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  • DOI: https://doi.org/10.1038/s41391-023-00751-6

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