Ki67 and prostate specific antigen are prognostic in metastatic hormone naïve prostate cancer

Authors

  • Vasiliki Spyratou a Department of Urology, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden
  • Eva Freyhult b Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
  • Anders Bergh c Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
  • Camilla Thellenberg-Karlsson d Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
  • Pernilla Wikström c Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
  • Karin Welén a Department of Urology, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden; e Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  • Andreas Josefsson a Department of Urology, Institute of Clinical Sciences, University of Gothenburg, Gothenburg, Sweden;f Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden; g Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden

DOI:

https://doi.org/10.1080/0284186X.2023.2254480

Keywords:

Metastatic prostate cancer, biomarker, androgen deprivation therapy, docetaxel, prostate specific antigen

Abstract

Background

For metastatic hormone naïve prostate cancer patients, androgen deprivation therapy (ADT) with escalation therapy including docetaxel and/or androgen targeting drugs is the standard therapy. However, de-escalation is preferable to avoid unnecessary side effects, especially from docetaxel, but markers to identify these patients are lacking. The purpose of the present study was to investigate the potential of PSA and Ki67 immunoreactive scores as prognostic and treatment-predictive markers.

Material and methods

Prostate biopsies from 92 patients with metastatic hormone naïve PC (PSA > 80 ng/mL or clinical metastases) were immunohistochemically evaluated for PSA and Ki67. Gene expression analysis was performed with Clariom D microarrays to identify the phenotypic profile associated with the immunohistochemistry scores of biopsies. Cox regression analysis for progression free survival after ADT adjustment for age, ISUP, and serum PSA and Kaplan-Meier analyses were performed to assess prognostic values of Ki67, PSA, and the Ki67/PSA ratio.

Results

The immunohistochemical score for PSA was the strongest prognostic factor for progression-free and overall survival after ADT. Consequently, the ratio between Ki67 and PSA displayed a stronger prognostic value than Ki67 itself. Further, mRNA expression data analysis showed an association between high Ki67/PSA ratio, cell-cycle regulation, and DNA damage repair. In an exploratory sub-analysis of 12 patients treated with early docetaxel as addition to ADT and matched controls, a high Ki67/PSA ratio showed potential to identify those who benefit from docetaxel.

Conclusion

PSA and Ki67 immunoreactive scores are prognostic in the metastatic hormone-sensitive setting, with PSA being superior. The combination of Ki67 and PSA did not give additional prognostic value. The results suggest immunohistochemical scoring of PSA to have potential to improve identification of patients responding well to ADT alone.

Downloads

Download data is not yet available.

Downloads

Additional Files

Published

2023-12-02

How to Cite

Spyratou, V., Freyhult, E., Bergh, A., Thellenberg-Karlsson, C., Wikström, P., Welén, K., & Josefsson, A. (2023). Ki67 and prostate specific antigen are prognostic in metastatic hormone naïve prostate cancer. Acta Oncologica, 62(12), 1698–1706. https://doi.org/10.1080/0284186X.2023.2254480

Issue

Vol. 62 No. 12 (2023): Acta Oncologica

Section

Articles