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Prevention of Prostate Cancer: Is It Effective?

This article discusses strategies, agents, and complementary medicine for preventing prostate cancer. It delves into ongoing trials and the implications of the Prostate Cancer Prevention Trial.

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Prevention of Prostate Cancer: Is It Effective?

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  1. Prevention Of Prostate Cancer: Is This The Way To Go? Per-Anders Abrahamsson Chairman & Professor Department of Urology Malmö University Hospital, Sweden

  2. Strategy to Reduce Mortality In Prostate Cancer Prevention Early diagnosis of prostate cancer

  3. Agents of Interest to Prevent Prostate Cancer • 5-[alpha]-reductase inhibitors • Selenium • vitamin E • vitamin D • cyclooxygenase-2 inhibitors • Lycopenes • green tea

  4. Complementary “preventive” Medicine In Prostate Cancer • Herbal medicine • green tea • garlic • Micronutrient supplements • lycopenes and other carotenoids • selenium • vitamin E • vitamin D • Dietary measures • soy protein and plant fibers • reduction in dietary fat Up to 50% of patients have used CAM CAM sales exceeds 2.5 billion $ in the US

  5. Vitamin E (Alpha-tocopherol)The ATBC Study • 29,133 Finnish male smokers 50-69 years old randomized • (1)alpha -tocopherol only • (2)beta -carotene only • (3) alpha-tocopherol plus beta-carotene • (4) placebo • Evaluated incidence of lung cancer and other cancers

  6. Vitamin E (Alpha-tocopherol)The ATBC study 1985-93 • Supplementation with alpha-tocopherol had no effect on lung cancer incidence but did reduce the incidence of prostate cancer by 34% (95% CI, 14%-48%) • Lung cancer effect disappeared in follow-up, but prostate prevention persisted

  7. Ongoing Trials • SELECT • Selenium, Vitamin E, Both, or Placebo • 8,100 men in each arm • 7-12 years of follow-up planned • APPOSE - Australian Prostate Cancer Prevention Trial Using Selenium • 200 µg/day selenium vs placebo • 2000 high risk men in each arm

  8. PREVENTION Until recently……… Not possible for many years to come But the PCPT data may ultimately change this scenario !?

  9. The Implications of the PCPT in terms of Clinical Practise Paris, December 19, 2005 A European Consensus Conference Abrahamsson & Teillac, Eur Urol, June 2006

  10. The Prostate Cancer Prevention Trial - Study design Enrollment 18,882 men randomized n=9459 Finasteride n=9423 Placebo Annual DRE And PSA for Seven years End-of-study Biopsy regardless Of PSA and DRE End-of-study Biopsy regardless Of PSA and DRE Study Group

  11. Gleason Score Total Number of Cancers Thompson IM, et al. New Engl J Med 2003;349:215-24

  12. Initial Thoughts on Grade • Observations made in letter to Editor of NEJM immediately after publication; • Risk of high-grade cancer did not increase over time; • If inducing HG cancer, the relative risk should increase over time; It did not.

  13. What Are the Potential Reasonsfor an Increased Grade? Was it due to an alteration in tumour grade, caused by finasteride?

  14. What Are the Potential Reasons for an Increased Grade? • Hormonal pathologic effect – probably not • Ascertainment artifact Reduced gland volume with finasteride Better sampling of gland More accurate grading (which is often higher)

  15. Gland Volume Artifact Hypothesis Assume no change in tumour with treatment Result in Placebo: Gleason 3+3 Result in Finasteride: Gleason 3+4 Gleason 4 Gleason 3

  16. Corrolary to Volume Artifact- How close is your grade to ‘true grade´ Finasteride – higher grade but more accurate grading Placebo – greater risk you missed the correct grade

  17. What Happens to Gleason Score – From Biopsy to Prostatectomy - …more commonly goes up. Sometimes goes down… 35 24 15 11 8 5 2 From: Bostwick DG. Amer J Clin Path 102(Suppl 1):S38, 1994

  18. How Does Our Hypothesis Play Out? FinasteridePlacebo Any ↑ at RP: 47/192 (24.5%) 83/272 (30.5%) No change: 107/192 (55.7%) 155/272 (57.0%) Any ↓ at RP: 38/192 (19.8%) 34/272 (12.5%)

  19. If You Had a HG Tumour at Prostatectomy, What Was the Likelihood that Biopsy Missed It? • Placebo – 50.0% • Finasteride – 29.7%

  20. Gland Volume Bias • There appears to have been some sort of bias in detection of high-grade disease • Most likely rationale – gland volume Recently verified by Kulkarni; J Urol 175:505, 2006

  21. Gleason Score – End-of-Study BiopsiesNumber of Cancers Not graded: Finasteride n=4, Placebo n=12

  22. PSA Performance? • Studied men in placebo and finasteride arms of PCPT • All had a biopsy and a PSA within one year of biopsy • Sensitivity and AUC for PSA compared between finasteride and placebo Thompson IM, AUA, Atlanta, 2006

  23. ROC’s AUC’s Cancer versus no Cancer: Finasteride .757, placebo .681, p <.001 Gleason > 7: Finasteride .838, placebo .781, p=.003 Gleason > 8: Finasteride .886, placebo .824, p=.071

  24. The Prostate Cancer Prevention Trial: Implications For Clinical Practice A European Consensus MeetingParis, December 19, 2005 Co-Chairmen: Pierre Teillac Per-Anders Abrahamsson

  25. Consensus Meeting Panelists From left to right: Jørgen Nordling, Manfred Wirth, Pierre Teillac, Per-Anders Abrahamsson, David Crawford (key note speaker on the PCPT data), Christopher Chapple, Adrian Joyce, Cle´ment-Claude Abbou, Jean-Louis Misset, Andrea Tubaro, Eduardo Solsona. Professor Pierre Teillac, France Professor Per-Anders Abrahamsson, Sweden Professor Clement Claude Abbou, France.Mr Christopher Chapple, United Kingdom Mr Adrian Joyce, United Kingdom. Professor Jean-Louis Misset, France Professor Jørgen Nordling, Denmark. Dr Eduardo Solsona, Spain Professor Andrea Tubaro, Italy. Professor Manfred Wirth, Germany

  26. PCPT: Background and Overview of Results (1) • Largest Chemoprevention study ever reported in the urological community and reports for the first time that medical intervention may reduce the incidence of diagnosed prostate cancer to a clinically meaningful extent (level 1b evidence)

  27. PCPT: Background and Overview of Results (2) • This study was initiated and funded by the National Cancer Institute for the National Institutes of Health of the USA • The results showed that finasteride reduced the risk of developing prostate cancer by 25% compared to placebo (24.4% placebo vs. 18.4% finasteride)

  28. Implications for PCa Chemoprevention • For men who are concerned about prostate cancer, • It may be appropriate to discuss chemoprevention with finasteride • In doing so, it is important to highlight both the benefits and potential side effects associated with long-term treatment

  29. Implications for PCa Chemoprevention • More data on health economic analyses are required before recommending widespread chemoprevention with finasteride

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