Skip to main content

Advertisement

SpringerLink
Log in

Dutasteride for the prevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia: results of a phase III randomized open-label 3-year trial

  • Original Article
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Purpose

High-grade prostatic intraepithelial neoplasia (HGPIN) is a potential precursor of prostate cancer (PCa), and patients with HGPIN are at high risk for PCa development. Objective of our study was to evaluate the efficacy of dutasteride 0.5 mg in PCa prevention among men with isolated HGPIN on biopsy.

Methods

This prospective, randomized, phase III, open-label 3-year trial assessed dutasteride versus active surveillance in patients with HGPIN. Patients were randomized to dutasteride 0.5 mg daily or active surveillance. Per-protocol prostate biopsies were performed at 6, 12, 24, and 36 months until cancer detection or study end. The primary end point was cancer-free survival (CFS). An intention-to-treat analysis was done for patients who underwent at least one per-protocol biopsy. An efficacy analysis was done for patients who completed the study. CFS was evaluated using Kaplan–Meier and log-rank analysis.

Results

In total, 220 men were randomized (dutasteride, n = 107; surveillance, n = 113). PCa was detected in 47.6: 49.1 % in the surveillance group and 45.9 % in the treatment group (p = 0.66). The detected PCa differentiation by Gleason score (GS) was GS 6 in 76.9 %, GS 7 in 19.8 %, and GS ≥ 8 in 3.3 %, with no difference between groups. The 3-year PCa-free survival was 43.6 % in the surveillance and 49.6 % in the dutasteride group (log rank p = 0.57). Limitations include a relatively high non-adherence rate, open-label design, and baseline sextant biopsy scheme.

Conclusions

Dutasteride 0.5 mg for 3 years did not lower the PCa detection rate but did not worsen detected PCa characteristics in men with HGPIN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Aboseif S, Shinohara K, Weidner N, Narayan P, Carroll PR (1995) The significance of prostatic intra-epithelial neoplasia. Br J Urol 76:355–359

    Article  CAS  PubMed  Google Scholar 

  2. Park S, Shinohara K, Grossfeld GD, Carroll PR (2001) Prostate cancer detection in men with prior high grade prostatic intraepithelial neoplasia or atypical prostate biopsy. J Urol 165:1554–1559

    Article  Google Scholar 

  3. Lefkowitz GK, Sidhou GS, Torre P, Lepor H, Taneja SS (2001) Is repeat prostate biopsy for high-grade prostatic intraepithelial neoplasia necessary after routine 12-core sampling? Urology 58:999–1003

    Article  CAS  PubMed  Google Scholar 

  4. Auskalnis S, Milonas D, Jievaltas M, Vaiciunas K, Mickevicius A, Gudinaviciene I (2010) The role of high-grade prostatic intraepithelial neoplasia for biochemical relapse of prostate carcinoma after radical prostatectomy. Medicina 46:604–610

    PubMed  Google Scholar 

  5. Qian J, Wollan P, Bostwick DG (1997) The extent of multicentricity of high-grade prostatic intraepithelial neoplasia in clinically localized prostatic adenocarcinoma. Hum Pathol 28:143–148

    Article  CAS  PubMed  Google Scholar 

  6. Klein EA, Thompson IM Jr, Tangen CM, Crowley JJ, Lucia MS, Goodman PJ, Minasian LM, Ford LG, Parnes HL, Gaziano JM, Karp DD, Lieber MM, Walther PJ, Klotz L, Parsons JK, Chin JL, Darke AK, Lippman SM, Goodman GE, Meyskens FL Jr, Baker LH (2011) Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 306:1549–1556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Fleshner NE, Kapusta L, Donnelly B, Tanguay S, Chin J, Hersey K, Anne Farley A, Jansz K, Siemens DR, Tripkov K, Lacombe L, Gleave M, Tu D, Parulekar WD (2011) Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium. J Clin Oncol 29:2386–2390

    Article  CAS  PubMed  Google Scholar 

  8. Marshall JR, Tangen CM, Sakr WA, Wood DP, Berry DL, Klein EA, Lippman SM, Parnes HL, Alberts DS, Jarrard DF, Lee WR, Gaziano JM, Crawford ED, Ely B, Ray M, Davis W, Minasian LM, Thompson IM Jr (2011) Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia: SWOG S9917. Cancer Prev Res 4:1761–1769

    Article  CAS  Google Scholar 

  9. Taneja SS, Morton R, Barnette G, Sieber P, Hancock ML, Steiner M (2013) Prostate cancer diagnosis among men with isolated high-grade intraepithelial neoplasia enrolled onto a 3-year prospective phase III clinical trial of oral toremifene. J Clin Oncol 31:523–529

    Article  CAS  PubMed  Google Scholar 

  10. Thomson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr (2003) The influence of finasteride on the development of prostate cancer. N Engl J Med 349:215–224

    Article  Google Scholar 

  11. Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, Pettaway CA, Tammela TL, Teloken C, Tindall DJ, Somerville MC, Wilson TH, Fowler IL, Rittmaster RS, REDUCE Study Group (2010) Effect of dutasteride on the risk of prostate cancer. N Engl J Med 362:1192–1202

    Article  CAS  PubMed  Google Scholar 

  12. Roehrborn CG, Andriole GL, Wilson TH, Castro R, Rittmaster RS (2011) Effect of dutasteride on prostate biopsy rates and the diagnosis of prostate cancer in men with lower urinary tract symptoms and enlarged prostates in the Combination of Avodart and Tamsulosin trial. Eur Urol 59:244–249

    Article  CAS  PubMed  Google Scholar 

  13. Fleshner NE, Lucia MS, Egerdie B, Aaron L, Eure G, Nandy I, Black L, Rittmaster RS (2012) Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial. Lancet 379:24–30

    Article  Google Scholar 

  14. Ross AE, Feng Z, Pierorazio PM, Landis P, Walsh PC, Carter BC, Trock BJ, Schaeffer EM (2012) Effect of treatment with 5-α reductase inhibitors on progression in monitored men with favourable-risk prostate cancer. BJUI 110:651–657

    Article  CAS  Google Scholar 

  15. Jones JS (2013) Prostate cancer diagnosis: PSA, biopsy and beyond, current clinical urology, current clinical urology. Springer, New York, pp 241–254

    Book  Google Scholar 

  16. Roscigno M, Scattoni V, Freschi M (2010) Diagnosis of high-grade prostatic intraepithelial neoplasia: the impact of the number of biopsy cores at initial sampling on cancer detection after a saturation re-biopsy. Arch Ital Urol Androl 82:242–247

    PubMed  Google Scholar 

  17. Eskicorapci SY, Guliyev F, Islamoglu E, Ergen A, Ozen H (2007) The effect of prior biopsy scheme on prostate cancer detection for repeat biopsy population: results of the 14-core prostate biopsy technique. Int Urol Nephrol 39:189–195

    Article  PubMed  Google Scholar 

  18. Gontero P, Marra G, Soria F, Oderda M, Zitella A, Baratta F, Chiorino G, Gregnanin I, Daniele L, Cattel L, Frea B, Brusa P (2015) A randomized double-blind placebo controlled phase I-II study on clinical and molecular effects of dietary supplements in men with precancerous prostatic lesions. Chemoprevention or “chemopromotion”? Prostate 75:1177–1186

    Article  CAS  PubMed  Google Scholar 

  19. Gee J, Baily H, Kim K, Kolesar J, Havighurst T, Tutsch KD, See W, Cohen MB, Street N, Levan L, Jarrard D, Wilding G (2013) Phase II open label, multi-center clinical trial of modulation of intermediate endpoint biomarkers by 1α-hydroxyvitamin D2 in patients with clinically localized prostate cancer and high grade pin. Prostate 73:970–978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Klein EA, Thompson IM (2012) Chemoprevention of prostate cancer: an update view. World J Urol 30:189–194

    Article  CAS  PubMed  Google Scholar 

  21. Marberger M, Freedland SJ, Andriole GL, Emberton M, Pettaway C, Montorsi F, Teloken C, Rittmaster RS, Somerville MC, Castro R (2012) Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study. BJUI 109:1162–1169

    Article  CAS  Google Scholar 

Download references

Author contributions

Daimantas Milonas had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. D Milonas performed protocol development, data collection, data analysis, and manuscript writing. S Auskalnis participated in data collection and data analysis. G Skulcius and I Gudinaviciene involved in data collection. M Jievaltas wrote the manuscript. S Joniau contributed to data analysis and manuscript writing.

Author information

Authors and Affiliations

  1. Department of Urology, Lithuanian Health Science University, Eiveniu 2, 50009, Kaunas, Lithuania

    Daimantas Milonas, Stasys Auskalnis, Giedrius Skulcius & Mindaugas Jievaltas

  2. Department of Pathology, Lithuanian Health Science University, Kaunas, Lithuania

    Inga Gudinaviciene

  3. Department of Urology, University Hospitals Leuven, Leuven, Belgium

    Steven Joniau

Authors
  1. Daimantas Milonas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stasys Auskalnis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giedrius Skulcius
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Inga Gudinaviciene
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mindaugas Jievaltas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Steven Joniau
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daimantas Milonas.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

The study protocol was approved by the Regional Biomedical Research Ethics Committee (Protocol ID BE-2-27), and the trial was registered in the ClinicalTrials.gov database (NCT00780754). ‘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.’

Informed consent

All patients signed written informed consent before trial enrollment.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Milonas, D., Auskalnis, S., Skulcius, G. et al. Dutasteride for the prevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia: results of a phase III randomized open-label 3-year trial. World J Urol 35, 721–728 (2017). https://doi.org/10.1007/s00345-016-1938-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-016-1938-8

Keywords

Search

Navigation