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Aggressiveness of Localized Prostate Cancer: the Key Value of Testosterone Deficiency Evaluated by Both Total and Bioavailable Testosterone: AndroCan Study Results

  • Yann Neuzillet
  • Jean-Pierre Raynaud
  • Jean-François Dreyfus
  • Camélia Radulescu
  • Mathieu Rouanne
  • Marc Schneider
  • Sylvie Krish
  • Morgan Rouprêt
  • Sarah J. Drouin
  • Eva Comperat
  • Marc Galiano
  • Xavier Cathelineau
  • Pierre Validire
  • Vincent Molinié
  • Jean Fiet
  • Franck Giton
  • Thierry Lebret
  • Henry Botto
Original Paper

Abstract

Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high. Improvements to patient selection and identification of at-risk patients are central to reducing mortality. We aimed to determine if cancer aggressiveness correlates with androgen levels in patients undergoing radical prostatectomy for localized PCa. We performed a prospective, multicenter cohort study between June 2013 and June 2016, involving men with localized PCa scheduled to undergo radical prostatectomy. Clinical and hormonal patient data (testosterone deficiency, defined by total testosterone (TT) levels < 300 ng/dL and/or bioavailable testosterone (BT) levels < 80 ng/dL) were prospectively collected, along with pathological assessment of preoperative biopsy and subsequent radical prostatectomy specimens, using predominant Gleason pattern (prdGP) 3/4 grading. Of 1343 patients analyzed, 912 (68%) had prdGP3 PCa and 431 (32%) had high-grade (prdGP4, i.e., ISUP ≥ 3) disease on prostatectomy specimens. Only moderate concordance in prdGP scores between prostate biopsies and prostatectomy specimens was found. Compared with patients with prdGP3 tumors (i.e., ISUP ≤ 2), significantly more patients with prdGP4 cancers had demonstrable hypogonadism, characterized either by BT levels (17.4% vs. 10.7%, p < 0.001) or TT levels (14.2% vs. 9.7%, p = 0.020). BT levels were also lower in patients with prdGP4 tumors compared to those with prdGP3 disease. Testosterone deficiency (defined by TT and/or BT levels) was independently associated with higher PCa aggressiveness. BT is a predictive factor for prdGP4 disease, and evaluating both TT and BT to define hypogonadism is valuable in preoperative assessment of PCa (AndroCan Trial: NCT02235142).

Keywords

Prostate cancer Androgens Gleason ISUP Hypogonadism Testosterone 

Notes

Acknowledgements

The authors wish to thank the subjects and healthcare staff who participated in this study and Chris Hintze (NCSS, LLC) for assistance with preliminary logistic regression model development.

Support

This study was funded by the Foch Foundation, a non-profit institution, and a grant of the French Ministry of Health/DGOS/CRC3F. Medical writing support was provided by Iain O’Neill on behalf of Newmed Medical Publishing, funded by the Foch Foundation.

Supplementary material

12672_2018_351_MOESM1_ESM.docx (55 kb)
ESM 1 (DOCX 54 kb)
12672_2018_351_MOESM2_ESM.docx (33 kb)
ESM 2 (DOCX 33 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yann Neuzillet
    • 1
  • Jean-Pierre Raynaud
    • 2
  • Jean-François Dreyfus
    • 3
  • Camélia Radulescu
    • 4
  • Mathieu Rouanne
    • 1
  • Marc Schneider
    • 5
  • Sylvie Krish
    • 6
  • Morgan Rouprêt
    • 7
  • Sarah J. Drouin
    • 7
  • Eva Comperat
    • 8
  • Marc Galiano
    • 9
  • Xavier Cathelineau
    • 9
  • Pierre Validire
    • 10
  • Vincent Molinié
    • 11
  • Jean Fiet
    • 12
  • Franck Giton
    • 12
  • Thierry Lebret
    • 1
  • Henry Botto
    • 1
  1. 1.Department of Urology, Hôpital FochUniversity of Versailles−Saint-Quentin-en-YvelinesSuresnesFrance
  2. 2.Sorbonne UniversityParisFrance
  3. 3.Department of Clinical Research and Innovation, Foch HospitalUniversity of Versailles−Saint-Quentin-en-YvelinesSuresnesFrance
  4. 4.Department of PathologyFoch HospitalSuresnesFrance
  5. 5.Department of UrologyLouis Pasteur HospitalColmarFrance
  6. 6.Department of PathologyLouis Pasteur HospitalColmarFrance
  7. 7.Department of Urology, Pitié Salpêtrière Hospital, Assistance Publique - Hôpitaux de ParisSorbonne UniversityParisFrance
  8. 8.Department of Pathology, Tenon Hospital, Assistance Publique - Hôpitaux de ParisSorbonne UniversityParisFrance
  9. 9.Department of Urology, Institut Mutualiste MontsourisParis−Descartes UniversityParisFrance
  10. 10.Department of Pathology, Institut Mutualiste MontsourisParis−Descartes UniversityParisFrance
  11. 11.Department of PathologyCentre Hospitalier de MartiniqueLe LamentinFrance
  12. 12.Inserm U955, Eq07, Recherches Translationnelles en oncogenèse génitaleCréteilFrance

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