5ARI and PSA: open questions

Abstract

No consensus has ever been reached on the predictive value of serum prostate specific antigen (PSA) for the diagnosis of prostate cancer. Limitations of PSA testing in clinical practice have been often discussed in the peer-reviewed literature following data derived from clinical trials such as the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study that showed a linear rise in the risk of prostate cancer with increasing PSA levels. Benign prostatic hyperplasia is a known confounding factor for the use of PSA as a marker of prostate cancer. Increased prostate volume observed with ageing, urinary retention, acute and chronic inflammatory conditions of the prostate, sexual activity and digital rectal examination may all cause an increase of PSA values. Both finasteride and dutasteride, 5-alpha reductase inhibitors (5ARI) used in the treatment of BPH, are known to induce a significant decrease of serum PSA levels close to 50%. The observed change in PSA values following 5ARI treatment has raised questions about the accuracy of PSA testing for the early diagnosis of prostate cancer in patients on finasteride/dutasteride treatment. Careful analysis of data from various clinical trials on pharmacological treatment of LUTS due to BPH suggested that the accuracy of PSA testing is not just maintained but rather increased following 5ARI use. Then, the question of PSA accuracy during 5ARI treatment can be considered closed.

Keywords

5-alpha reductase inhibitors Dutasteride Finasteride Prostate specific antigen Benign prostatic hyperplasia Prostate cancer Inibitori delle 5-alfa reduttasi Antigene prostatico specifico Iperplasia prostatica benigna Carcinoma prostatico

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References

Crawford

Abrahamsson

PSA-based screening for prostate cancer: how does it compare with other cancer screening tests?

Eur Urol 2008; 54 (2): 262–273.

Thompson

Pauler Ankerst

Chi

Prediction of prostate cancer for patients receiving finasteride: results from the Prostate Cancer Prevention Trial. J Clin Oncol 2007; 25 (21): 3076–3081.

Andriole

Humphrey

Ray

Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer. J Urol 2004; 172 (3): 915–919.

Andriole

Bostwick

Brawley

The effect of dutasteride on the usefulness of prostate specific antigen for the diagnosis of high grade and clinically relevant prostate cancer in men with a previous negative biopsy: results from the REDUCE study. J Urol 2011; 185 (1): 126–131.

Thompson

Chi

Ankerst

Effect of finasteride on the sensitivity of PSA for detecting prostate cancer. J Natl Cancer Inst 2006; 98 (16): 1128–1133.

Andriole

Guess

Epstein

Treatment with finasteride preserves usefulness of prostate-specific antigen in the detection of prostate cancer: results of a randomized, double-blind, placebo-controlled clinical trial. PLESS Study Group. Proscar Long-term Efficacy and Safety Study. Urology 1998; 52 (2): 195–201.

Andriole

Bostwick

Brawley

Effect of dutasteride on the risk of prostate cancer. N Engl J Med 2010; 362 (13): 1192–1202.

Marberger

Freedland

Andriole

Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study. BJU Int 2012; 109 (8): 1162–1169.

Klomp

Hendrikx

Keyzer

The effect of transrectal ultrasonography (TRUS) including digital rectal examination (DRE) of the prostate on the level of prostate specific antigen (PSA). Br J Urol 1994; 73 (1): 71–74.