Does finasteride prevent or promote prostate cancer?
Published in Health News and Evidence
Date published: About this date
Summary | Practice points | When is a 5-ARI indicated? | Does finasteride induce high-grade prostate cancer? | 5-ARIs decrease PSA levels | Do 5-ARIs have beneficial effects in prostate cancer reduction? | 5-ARI FDA warnings | Patient information | References
5-alpha reductase inhibitors (5-ARIs) are TGA approved in Australia for treatment of benign prostatic hypertrophy and male baldness.1 Their effect is associated with a reduction in PSA levels, which has prompted studies to determine whether these medicines may modify the risk of prostate cancer.2
Ten years ago the results of the Prostate Cancer Prevention Trial (PCPT) suggested, paradoxically, that the 5-ARI finasteride decreased the risk of low-grade prostate cancer but at the same time increased the risk of high-grade cancer.2
In 2011 the FDA announced ‘the 5-ARI class of drugs has been revised to include new safety information about the increased risk of being diagnosed with a more serious form of prostate cancer (high-grade prostate cancer)’.3
A recent follow-up study (up to 18 years) has confirmed the findings of the PCPT but further demonstrated that, although high-grade prostate cancer was more common in the finasteride group compared with placebo, finasteride had no significant effect on overall survival.4
This indicates that finasteride treatment may mask early detection of low-grade tumours by reducing PSA levels,4 thereby reducing the incidence of ‘overdiagnosis’ (early detection of cancers that may never cause harm in a person’s lifetime).
The increase in high-grade cancer diagnoses in the treated men may reflect lower detection rates at early stage of tumour development or, potentially, an increase in high-grade tumour development.5
There is no evidence to support the use of 5-ARIs for prostate cancer prevention although they may reduce the incidence of overdiagnosis.4-6
- Treatment with finasteride reduces the risk of being diagnosed with low-grade prostate cancer
But there is an increased risk of a later diagnosis of high-grade prostate cancer.2,4
- In trials, overall mortality was not affected by the impact of finasteride on incidence of diagosis4
After 18 years follow-up there was no significant increase in mortality among men receiving finasteride.4
- There is no evidence to support the use of 5-ARIs for prevention of prostate cancer3
However, men who choose to have regular PSA testing may benefit from a 5-ARI to reduce the risk of overdiagnosis, although it is not indicated for this purpose in Australia.5
- 5-ARIs are associated with around a 50% reduction in serum PSA levels7,8
Be aware that a confirmed increase in PSA level in a patient taking a 5-ARI, for whatever reason, may signal the presence of high-grade prostate cancer.3
- One way to reduce the harm of overdiagnosis resulting from PSA screening is to choose not to be screened.5
5-ARIs such as finasteride and dutasteride are currently indicated in Australia to treat men with symptomatic benign prostatic hypertophy (BPH). Finasteride is also indicated for the treatment of male-pattern hair loss.1
5-ARIs reduce symptoms of BPH by inhibiting the conversion of testosterone into dihydrotestosterone (DHT), which stimulates prostate tissue proliferation. This reduces prostate size, resulting in improved urinary flow, and prevents progression of BPH in the longer term.9,10
There is abundant evidence that androgens influence the development of prostate cancer.11-13 The availability of 5-ARIs, which reduce androgen levels, prompted the PCPT study, which aimed to establish whether finasteride reduces the prevalence of prostate cancer among healthy men.2
5-ARIs available in Australia1
||Benign prostatic hyperplasia
||5 mg once daily
|Androgenetic alopecia||1 mg once daily
|Dutasteride||Benign prostatic hyperplasia
||500 micrograms once daily
|Benign prostatic hyperplasia
||500 micrograms once daily
in combination with controlled-release
tamsulosin 400 micrograms once daily
While the PCPT showed that finasteride reduced the incidence of low-grade prostate cancer detection, the study authors suggested it may directly induce high-grade prostate cancer by:
- reducing the level of intracellular dihydrotestosterone within the prostate — there is evidence that prostate tumours that develop in men with low testosterone levels have higher Gleason grades and poorer prognosis than those that develop in men with normal testosterone levels2,14-16
- selecting for high-grade tumours by inhibiting low-grade tumours.2
In the follow-up study the 15-year rate of survival in each of the two groups was about 78%.4 If the increased incidence of high-grade prostate cancers was induced by finasteride, an increase in mortality among men receiving finasteride would have been expected.4
However, a link between finasteride and high-grade prostate cancer development cannot be excluded, as noted in the results of the European Randomized Study of Screening for Prostate Cancer trial,17 a small difference in prostate-cancer mortality can exist in the absence of a difference in all-cause mortality.
Whether the use of finasteride has a positive or a negative effect on prostate-cancer– specific mortality remains unknown, but either way the effect is probably very small and does not result in any difference in all-cause mortality.5
5-ARIs decrease PSA levels
Be aware that treatment with 5-ARIs causes about a 50% reduction in PSA levels by 6 months; however, individual patients receiving 5-ARIs may experience varying decreases in PSA level.7,8
Therefore, any confirmed increase in a person’s PSA level while on a 5-ARI may signal the presence of prostate cancer, and the patient should be evaluated, even if the increased PSA level is in the normal range for men not taking a 5-ARI.3
Currently there is insufficient evidence to determine whether early detection of prostate cancer using PSA testing reduces cancer mortality or improves disease outcomes, although the latest evidence suggests any potential benefit is only likely to be small.17,18 For more information on PSA tests see Limitations of prostate specific antigen (PSA) tests.
The PCPT found a meaningful reduction in prostate cancer incidence — in the original trial there was a relative reduction of 38% in the risk of prostate cancer with a Gleason grade of 2–6.4
As most of the morbidity associated with prostate cancer occurs during the diagnosis and management of the disease, a treatment that decreases the incidence of overdiagnosis of early-stage disease may reduce associated harms such as repeated screening tests and complications due to biopsies.4-6
In all cases advise your patients that taking finasteride will not reduce the risk of mortality from prostate cancer.
In 2011 the FDA mandated revisions to the labels for 5-ARIs, stating that they may ‘increase the risk of high-grade prostate cancer’ and are ‘not approved for the prevention of prostate cancer’, based on the results of the PCPT and the REDUCE* trial.3
The Therapeutic Goods Administration is exploring the latest findings reported here and the sponsors' Product Information for 5-ARIs has been updated to reflect the findings of the PCPT and REDUCE trials.19,20
* The Reduction by Dutasteride of Prostate Cancer Events trial evaluated the daily use of dutasteride 0.5 mg versus placebo for 4 years, for the reduction in the risk of prostate cancer in men at least 50–75 years old.21
- Prostate cancer patient support guide – The early detection of prostate cancer in general practice: supporting patient choice
- Cancer Council Australia – Information on prostate cancer
- Australian Medicines Handbook 2013. Adelaide: Australian Medicines Handbook Pty Ltd, 2013.
- Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003;349:215–24. [PubMed]
- U.S. Food and Drug Administration. FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer. 2011. http://www.fda.gov/drugs/drugsafety/ucm258314.htm (accessed 21 August 2013).
- Thompson IM Jr, Goodman PJ, Tangen CM, et al. Long-term survival of participants in the prostate cancer prevention trial. N Engl J Med 2013;369:603–10. [PubMed]
- LeFevre M. A role for finasteride in the prevention of prostate cancer? N Engl J Med 2013;369:670–1. [PubMed]
- McCarthy M. Finasteride for prostate cancer prevention has no effect on survival, study finds. BMJ 2013;347:f5203. [PubMed]
- Guess HA, Gormley GJ, Stoner E, et al. The effect of finasteride on prostate specific antigen: review of available data. J Urol 1996;155:3–9. [PubMed]
- Marks LS, Andriole GL, Fitzpatrick JM, et al. The interpretation of serum prostate specific antigen in men receiving 5alpha-reductase inhibitors: a review and clinical recommendations. J Urol 2006;176:868–74. [PubMed]
- McConnell JD, Roehrborn CG, Bautista OM, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003;349:2387–98. [PubMed]
- Miller J, Tarter TH. Combination therapy with dutasteride and tamsulosin for the treatment of symptomatic enlarged prostate. Clin Interv Aging 2009;4:251–8. [PubMed]
- Hsing AW, Reichardt JK, Stanczyk FZ. Hormones and prostate cancer: current perspectives and future directions. Prostate 2002;52:213–35. [PubMed]
- Ross RK, Bernstein L, Lobo RA, et al. 5-alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males. Lancet 1992;339:887–9. [PubMed]
- Giovannucci E, Stampfer MJ, Krithivas K, et al. The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc Natl Acad Sci U S A 1997;94:3320–3. [PubMed]
- Ishikawa S, Soloway MS, Van der Zwaag R, et al. Prognostic factors in survival free of progression after androgen deprivation therapy for treatment of prostate cancer. J Urol 1989;141:1139–42. [PubMed]
- Schatzl G, Madersbacher S, Haitel A, et al. Associations of serum testosterone with microvessel density, androgen receptor density and androgen receptor gene polymorphism in prostate cancer. J Urol 2003;169:1312–5. [PubMed]
- Prehn RT. On the prevention and therapy of prostate cancer by androgen administration. Cancer Res 1999;59:4161–4. [PubMed]
- Schroder FH, Hugosson J, Roobol MJ, et al. Prostate-cancer mortality at 11 years of follow-up. N Engl J Med 2012;366:981–90. [PubMed]
- Andriole GL, Crawford ED, Grubb RL III, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310–9. [PubMed]
- Merck Sharp & Dohme (Australia) Pty Limited. Proscar Approved Product Information. August 2013. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03378-3 (accessed 12 September 2013).
- GlaxoSmithKline. Approved Product Information Avodart Soft Capsules. July 2013. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-07763-3 (12 September 2013).
- Andriole GL, Bostwick DG, Brawley OW, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med 2010;362:1192–202. [PubMed]