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The PCPT-Does finasteride cause high-grade prostate cancer

Created: 17/3/2007
Updated: 17/3/2007

 

THE PCPT- Finasteride and high-grade prostate cancer

High grade prostate cancer (gleason 8,9,10) was found in 37% of tumours in the finasteride group and 22.2% of tumours in the placebo group

Does finasteride cause high-grade prostate cancer?

  • The incidence of high grade disease was higher in the finasteride group. However, this difference was seen in the 1st year of the study, and the subsequent incidence of high grade disease was similar between the 2 groups for the remainder of the study. If finasteride does cause high grade disease, an increasing number of high grade tumours would be expected to occur throughout the entire study period

  • Further histological examination of the high-grade tumours identified has subsequently been performed. Despite having smaller prostates and an equivalent number of biopsies, patients with high-grade disease in the finasteride group were less likely to have bilateral disease. Furthermore, there was no difference in other markers of tumour aggressiveness between to 2 groups

What are the potential explanations of the observation?

Alteration to histology

  • Androgen deprivation therapy has been shown to consistently cause histological changes in prostate tissue which mimic high grade prostate cancer
  • It is possible therefore that finasteride may exert a similar effect
  • However, this potential effect of finasteride on histological grading has not been in observed in a variety of other studies including a review of data from PLESS

Prostate volume

  • Finasteride reduces prostate volume. It is well known that prostate cancer detection rates decrease with increasing volume and accuracy of tumour detection and grading improves with smaller tumours
  • Further analysis of the PCPT data indicate that the change in prostate volume as a result of finasteride may well be responsible for the increased detection of high grade disease

PSA Effect

  • The high grade tumours were identified following biopsies carried for a raised PSA
  • The difference in high grade disease between the 2 groups was not seen when comparing end-of-study biopsies and biopsies performed for an abnormal DRE or abnormal DRE plus a raised PSA
  • A subset analysis of the PCPT concentrating on patients who had no cause for a biopsy during the study, has demonstrated that as PSA increases so does the prevalence of cancer including high grade disease
  • The suggestion has been made that finasteride improves the performance of PSA in detecting cancer-thereby leading to an increase in the detection of all cancers including higher grade tumours

Conclusions

  • The increase in high grade disease in the finasteride arm is probably artefact and due to a decrease in prostate volume and improved performance in PSA
  • It appears that finasteride does not have a significant effect on histology and cannot be used as an explanation for the increase in high grade disease
  • Importantly, if prostate volume decrease does lead to an increase in cancer detection, the reduction in prostate cancer risk with finasteride may actually be higher than reported

Click here for a summary of the PCPT


ArticleDate:20070317
SiteSection: Article
 
   
    
                                            



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