Current Treatment Options in Oncology

, Volume 7, Issue 5, pp 346–354 | Cite as

Should finasteride be used to prevent prostate cancer?

  • Neil Fleshner
  • Girish Kulkarni
Article

Opinion statement

Prostate cancer is an important public health problem. Chemoprevention offers an attractive solution because it may lead to decreased disease-specific mortality. Furthermore, because many men are treated radically for prostate cancers that pose little or no threat to life, chemoprevention may also provide an excellent strategy for diminishing treatment-related costs and adverse effects such as erectile and urinary dysfunction. The Prostate Cancer Prevention Trial was a 7-year randomized study of finasteride versus placebo among men aged older than 55 years. All men were intended to have a prostate biopsy at study conclusion. At trial's end, there was a 25% reduction in period prevalence in all prostate cancers (24.4% for placebo vs 18.4% for finasteride). This represents a 6% absolute risk reduction. A larger number of higher-grade cancers were noted among men randomized to finasteride, which post hoc analyses and studies suggest are almost certainly related to previously unrecognized biases in trial design. There continues to be great debate as to the clinical significance of the cancers prevented. It is our opinion that among men who warrant 5-alpha reductase inhibitors (5ARIs) as part of their benign prostatic hyperplasia regimen, cancer prevention should be recognized as an additional benefit of treatment. Furthermore, men with high risk of clinically significant prostate cancer, such as significant family history, abnormal prostate biopsy histologies, and African descent, should be made aware of these findings. Men with significant anxiety or concern about prostate cancer should also be made aware of the risks and benefits of this therapy. Additional trials of antiestrogens, micronutrients, and other 5ARIs, which will mature over the next 2 to 5 years, will better define the role of 5ARIs in prostate cancer chemoprevention.

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References and Recommended Reading

  1. 1.
    Burke HB, Bostwick DG, Meiers I, Montironi R: Prostate cancer outcome: epidemiology and biostatistics. Anal Quant Cytol Histol 2005, 27:211–217.PubMedGoogle Scholar
  2. 2.
    Akazaki K, Stemmermann G: Comparative study of latent carcinoma of the prostate among Japanese in Japan and Hawaii. J Natl Cancer Inst 1973, 50:1137–1144.PubMedGoogle Scholar
  3. 3.
    Arredondo SA, Elkin EP, Marr PL, et al.: CaPSURE Investigators. Impact of comorbidity on health-related quality of life in men undergoing radical prostatectomy: data from CaPSURE. Urology 2006, 67:559–565.PubMedCrossRefGoogle Scholar
  4. 4.
    Sakr W, Haas G, Cassin B: The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients. J Urol 1993, 150:379–385.PubMedGoogle Scholar
  5. 5.
    Wu CP, Gu FL: The prostate in eunuchs. Prog Clin Biol Res 1991, 370:249–255.PubMedGoogle Scholar
  6. 6.
    Wilson SS, Crawford ED: Controversies of androgen ablation therapy for metastatic prostate cancer. Curr Pharm Des 2006, 12:799–805.PubMedCrossRefGoogle Scholar
  7. 7.
    Kaplan SA, McConnell JD, Roehrborn CG, et al.: Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. Combination therapy with doxazosin and finasteride for benign prostatic hyperplasia in patients with lower urinary tract symptoms and a baseline total prostate volume of 25 ml or greater. J Urol 2006, 175:217–220.PubMedCrossRefGoogle Scholar
  8. 8.
    Thompson IM, Goodman PJ, Tangen CM, et al.: The influence of finasteride on the development of prostate cancer. N Engl J Med 2003, 349:215–224. This key article reports the results of the PCPT using finasteride.PubMedCrossRefGoogle Scholar
  9. 9.
    Pannek J, Marks LS, Pearson JD, et al.: Influence of finasteride on free and total serum prostate specific antigen levels in men with benign prostatic hyperplasia. J Urol 1998, 159:449–453.PubMedCrossRefGoogle Scholar
  10. 10.
    Albertsen PC, Hanley JA, Fine J: 20-year outcomes following conservative management of clinically localized prostate cancer. JAMA 2005, 293:2095–2101.PubMedCrossRefGoogle Scholar
  11. 11.
    Gleason DF: Histological grading of prostate cancer: a perspective. Hum Pathol 1992, 23:273–279.PubMedCrossRefGoogle Scholar
  12. 12.
    Epstein JI, Allsbrook WC, Amin MB, Egevad LL: Update on Gleason grading system for prostate cancer: results of an international consensus conference of urologic pathologists. Adv Anat Pathol 2006, 13:57–59.PubMedCrossRefGoogle Scholar
  13. 13.
    Armas OA, Aprikian AG, Melamed J, et al.: Clinical and pathobiological effects of neoadjuvant total androgen ablation therapy on clinically localized prostatic adenocarcinoma. Am J Surg Pathol 1994, 18:979–991.PubMedCrossRefGoogle Scholar
  14. 14.
    Civantos F, Soloway MS, Pinto JE: Histopathological effects of androgen deprivation in prostatic cancer. Semin Urol Oncol 1996, 4(Suppl 2):22–31.Google Scholar
  15. 15.
    Yang XJ, Lecksell K, Short K, et al.: Does long-term finasteride affect the histological features of benign prostate tissue and prostate cancer on needle biopsy? PLESS study group. Urology 1999, 53:696–700.PubMedCrossRefGoogle Scholar
  16. 16.
    Rubin MA, Allory Y, Molinie V, et al.: Effects of long-term finasteride treatment on prostate cancer morphology and clinical outcome. Urology 2005, 66:930–934.PubMedCrossRefGoogle Scholar
  17. 17.
    Kulkarni GS, Al-Azab R, Lockwood G, et al.: Evidence for a biopsy derived grade artifact among larger prostate glands. J Urol 2006, 175:505–509. This key publication first describes the volume/grade artifact.PubMedCrossRefGoogle Scholar
  18. 18.
    Marks LS, Partin AW, Dorey FJ, et al.: Long-term effects of finasteride on prostate tissue composition. Urology 1999, 53:574–580.PubMedCrossRefGoogle Scholar
  19. 19.
    Thompson IM, Chen C, Goodman P, et al.: Comparison of the operating characteristics of PSA for prostate cancer detection for finasteride and placebo in the prostate cancer prevention trial. J Urol 2006, 175:153.Google Scholar
  20. 20.
    Unger JM, LeBlanc M, Thompson IM, Coltman CA Jr: The person-years saved model and other methodologies for assessing the population impact of cancerprevention strategies. Urol Oncol 2004, 22:362–368. This was the first decision analysis based on PCPT data.PubMedGoogle Scholar
  21. 21.
    Lotan Y, Cadeddu JA, Lee JJ, et al.: Implications of the prostate cancer prevention trial: a decision analysis model of survival outcomes. J Clin Oncol 2005, 23:1911–1920.PubMedCrossRefGoogle Scholar
  22. 22.
    Zeliadt SB, Etzioni RD, Penson DF, et al.: Lifetime implications and cost-effectiveness of using finasteride to prevent prostate cancer. Am J Med 2005, 118:850–857.PubMedCrossRefGoogle Scholar
  23. 23.
    Fleshner N, Al Azab R: Prostate cancer: chemoprevention update 2005. Can J Urol 2005, 12(Suppl 2):2–4.PubMedGoogle Scholar
  24. 24.
    Fleshner N, Bagnell PS, Klotz L, Venkateswaran V: Dietary fat and prostate cancer. J Urol 2004, 171:S19-S24.PubMedCrossRefGoogle Scholar
  25. 25.
    Ornish D, Weidner G, Fair WR, et al.: Intensive lifestyle changes may affect the progression of prostate cancer. J Urol 2005, 174:1065–1069; discussion 1069-1070.PubMedCrossRefGoogle Scholar
  26. 26.
    Fleshner NE: Vitamin E and prostate cancer. Urol Clin North Am 2002, 29:107–113, ix.PubMedCrossRefGoogle Scholar
  27. 27.
    Heinonen OP, Albanes D, Virtamo J, et al.: Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 1998, 90:440–446.PubMedCrossRefGoogle Scholar
  28. 28.
    Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al.: Metaanalysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 2005, 142:37–46.PubMedGoogle Scholar
  29. 29.
    Lonn E, Bosch J, Yusuf S, et al.: HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005, 293:1338–1347.PubMedCrossRefGoogle Scholar
  30. 30.
    Nelson MA, Porterfield BW, Jacobs ET, Clark LC: Selenium and prostate cancer prevention. Semin Urol Oncol 1999, 17:91–96.PubMedGoogle Scholar
  31. 31.
    Venkateswaran V, Klotz LH, Fleshner NE: Selenium modulation of cell proliferation and cell cycle biomarkers in human prostate carcinoma cell lines. Cancer Res 2002, 62:2540–2545.PubMedGoogle Scholar
  32. 32.
    Fair WR, Fleshner NE, Heston W: Cancer of the prostate: a nutritional disease. Urology 1997, 50:840–848.PubMedCrossRefGoogle Scholar
  33. 33.
    Giovannucci E: Tomato products, lycopene, and prostate cancer: a review of the epidemiological literature. J Nutr 2005, 135:2030S-2031S.PubMedGoogle Scholar
  34. 34.
    Ansari M, Ansari S: Lycopene and prostate cancer. Future Oncol 2005, 1:425–430.PubMedCrossRefGoogle Scholar
  35. 35.
    Desgrandchamps F: Who will benefit from combination therapy? The role of 5 alpha reductase inhibitors and alpha blockade: a reflection from MTOPS. Curr Opin Urol 2004, 14:17–20.PubMedCrossRefGoogle Scholar
  36. 36.
    Carter BS, Bova GS, Beaty TH, et al.: Hereditary prostate cancer: epidemiologic and clinical features. J Urol 1993, 150:797–802.PubMedGoogle Scholar
  37. 37.
    Tomlins SA, Mehra R, Rhodes DR, et al.: TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Res 2006, 66:3396–3400.PubMedCrossRefGoogle Scholar
  38. 38.
    Spangler E, Zeigler-Johnson CM, Malkowicz SB, et al.: Association of prostate cancer family history with histopathological and clinical characteristics of prostate tumors. Int J Cancer 2005, 113:471–474.PubMedCrossRefGoogle Scholar
  39. 39.
    Djavan B, Remzi M, Schulman CC, et al.: Repeat prostate biopsy: who, how and when? A review. Eur Urol 2002, 42:93–103.PubMedCrossRefGoogle Scholar
  40. 40.
    Patel T, Huang G, Lepor H, Taneja SS: Are cancers diagnosed in long-term follow up of HGPIN clinically significant. J Urol 2006, 175:480.CrossRefGoogle Scholar
  41. 41.
    Epstein JI, Herawi M: Prostate needle biopsies containing prostatic intraepithelial neoplasia or atypical foci suspicious for carcinoma: implications for patient care. J Urol 2006, 175:820–834.PubMedCrossRefGoogle Scholar
  42. 42.
    Jones RA, Wenzel J: Prostate cancer among African-American males: understanding the current issues. J Natl Black Nurses Assoc 2005, 16:55–62.PubMedGoogle Scholar
  43. 43.
    Dutta Roy S, Philip J, Javle P: Trends in prostate cancer incidence and survival in various socioeconomic classes: a population-based study. Int J Urol 2005, 12:644–653.CrossRefGoogle Scholar
  44. 44.
    Taneja SS, Smith MR, Dalton JT, et al.: Toremifene--a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy. Expert Opin Investig Drugs 2006, 15:293–305.PubMedCrossRefGoogle Scholar
  45. 45.
    Lippman SM, Goodman PJ, Klein EA, et al.: Designing the selenium and vitamin E cancer prevention trial (SELECT). J Natl Cancer Inst 2005, 97:94–102.PubMedCrossRefGoogle Scholar
  46. 46.
    Andriole GL, Roehrborn C, Schulman C, et al.: Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia. Urology 2004, 64:537–541; discussion 542-543.PubMedCrossRefGoogle Scholar
  47. 47.
    Thomas LN, Lazier CB, Gupta R, et al.: Differential alterations in 5alpha-reductase type 1 and type 2 levels during development and progression of prostate cancer. Prostate 2005, 63:231–239.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2006

Authors and Affiliations

  • Neil Fleshner
    • 1
  • Girish Kulkarni
  1. 1.University Health NetworkTorontoCanada

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