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Five-alpha reductase inhibitors in men undergoing active surveillance for prostate cancer: impact on treatment and reclassification after 6 years follow-up

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Abstract

Objectives

To evaluate the impact of 5-alpha reductase inhibitors (5-ARIs) on definitive treatment (DT) and pathological progression (PP) in patients on active surveillance (AS) for prostate cancer.

Methods

We identified 361 consecutive patients, from an IRB-approved database, on AS for prostate cancer with minimum 2 years follow-up. Patients were grouped into two cohorts, those using 5-ARIs (5-ARI; n = 119) or not using 5-ARIs (no 5-ARI; n = 242). Primary and secondary endpoints were treatment-free survival (TFS) and PP-free survival (PPFS), which were evaluated by Kaplan–Meier analysis. Univariate and multivariable cox regression analysis were used to identify predictors for PP and DT. A p value < 0.05 was considered statistically significant.

Results

Baseline characteristics and the prostate biopsy rate were similar between the two groups. Median (range) follow-up was 5.7 (2.0–17.2) years. Five-year and 10-year TFS was 92% and 59% for the 5-ARI group versus 80% and 51% for the no 5-ARI group (p = 0.005), respectively. Five-year and 10-year PPFS was 77% and 41% for the 5-ARI group versus 70% and 32% for the no 5-ARI group (p = 0.04), respectively. Independent predictors for treatment and PP were not taking 5-ARIs (p = 0.005; p = 0.02), entry PSA > 2.5 ng/mL (p = 0.03; p = 0.01) and Gleason pattern 4 on initial biopsy (p < 0.001; p < 0.001), respectively. The main limitation is the retrospective study design.

Conclusions

5-ARIs reduces reclassification and cross-over to treatment in men on active surveillance for prostate cancer. Further, taking 5-ARIs was an independent predictor for prostate cancer progression and definitive treatment.

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Abbreviations

5-AR:

5-Alpha reductase

5-ARIs:

5-Alpha reductase inhibitors

DHT:

Dihydrotestosterone

DT:

Definitive treatment

LUTS:

Lower urinary tract symptoms

No 5-ARI:

Not using 5-ARIs

PP:

Pathological progression

PSA:

Prostate-specific antigen

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Funding

This study was supported in part by the CA205058-01 R01 grant from the National Institutes of Health/National Cancer Institute (ALA and ISG) and by the Australasian Urological Foundation (ANA).

Author information

Authors and Affiliations

  1. USC Institute of Urology and Catherine and Joseph Aresty Department of Urology, Center for Image-Guided Surgery and Focal Therapy, Keck School of Medicine, University of Southern California, 1441 Eastlake Ave, Suite 7416, Los Angeles, CA, 90089, USA

    Akbar N. Ashrafi, Toshitaka Shin, Arnaud Marien, Sunao Shoji, Tsuyoshi Iwata, Atsuko Iwata, Masakatsu Oishi, Sameer Chopra, Jie Cai, Inderbir S. Gill & Andre Luis Abreu

  2. Department of Surgery, North Adelaide Local Health Network, South Australia Health, Adelaide, South Australia, Australia

    Akbar N. Ashrafi

  3. Discipline of Surgery, The University of Adelaide, Adelaide, South Australia, Australia

    Akbar N. Ashrafi

  4. College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia

    Akbar N. Ashrafi

  5. Department of Urology, Oita University, Oita, Japan

    Toshitaka Shin

  6. Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Thomas Clifford & Andre Luis Abreu

  7. Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Tsuyoshi Iwata, Atsuko Iwata, Masakatsu Oishi & Osamu Ukimura

  8. Prostate Institute of America, Ventura, CA, USA

    Duke Bahn

Authors
  1. Akbar N. Ashrafi
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  2. Toshitaka Shin
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  3. Arnaud Marien
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  4. Thomas Clifford
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  5. Sunao Shoji
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  6. Tsuyoshi Iwata
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  7. Atsuko Iwata
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  8. Masakatsu Oishi
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  9. Sameer Chopra
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  10. Jie Cai
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  11. Osamu Ukimura
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  12. Duke Bahn
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  13. Inderbir S. Gill
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  14. Andre Luis Abreu
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Contributions

All authors contributed to the study's conception and design. Material preparation, data collection, and analysis were performed by ANA, TS, AM, TC, SS, TI, AI, SC and ALA. The first draft of the manuscript was written by ANA, TS, ISG and ALA and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Andre Luis Abreu is consultant for Koelis and was proctor in training for Steba Biotech. Inderbir Gill is a non-paid consultant for Steba Biotech.

Corresponding author

Correspondence to Andre Luis Abreu.

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Research involving human participants and/or animals (ethical approval)

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Ashrafi, A.N., Shin, T., Marien, A. et al. Five-alpha reductase inhibitors in men undergoing active surveillance for prostate cancer: impact on treatment and reclassification after 6 years follow-up. World J Urol 39, 3295–3307 (2021). https://doi.org/10.1007/s00345-021-03644-2

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  • DOI: https://doi.org/10.1007/s00345-021-03644-2

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