Editing Prostate Cancer: Prevention (section)

== 5-alpha reductase inhibitors (5-ARIs) ==
* '''<span style="color:#ff0000">Randomized trials (PCPT and REDUCE, see below ) evaluating 5-ARIs for prostate cancer prevention have found that their use results in (2)</span>'''
*# '''<span style="color:#ff0000">≈5% reduced risk of cancer</span>'''
*# '''<span style="color:#ff0000">Slight increased risk of high grade cancer</span>''' 
*#* '''<span style="color:#ff0000">Increased "risk" of high grade cancer is thought to be due to the higher probability of targeting a focus of high grade disease in a 5-ARI-induced smaller size gland</span>'''
*'''FDA concluded that 5-ARIs did not have a favourable risk-benefit profile for the chemoprevention of prostate cancer'''
** FDA assessment: for every 150-200 men treated with a 5-ARI, 1 additional man would be diagnosed with high-grade prostate cancer to avert 3-4 low-grade cancers.

=== <span style="color:#ff00ff">Prostate Cancer Prevention Trial (PCPT) (NEJM 2003)</span> ===
*'''<span style="color:#ff0000">Objective: determine whether a 5-ARI could reduce the risk of prostate cancer</span>'''
* '''<span style="color:#ff0000">Population: 18,882 men aged ≥ 55 years with normal DRE and PSA ≤ 3.0ng/ml</span>'''
* '''<span style="color:#ff0000">Randomized to finasteride</span>''' (5mg) '''<span style="color:#ff0000">vs. placebo daily</span>''' 
** '''<span style="color:#ff0000">Biopsy was recommended at the end of the study (7 years) for all participants, or “for cause” in men who had a PSA ≥ 4 ng/ml (adjusted for the effect of finasteride) or an abnormal DRE</span>'''
* '''<span style="color:#ff0000">Primary end point: prevalence of prostate cancer during the 7 years of the study</span>'''
* '''<span style="color:#ff0000">Results:</span>''' 
** 9060 (48%) evaluable for primary end point
** '''<span style="color:#ff0000">Significantly reduced risk of incident prostate cancer with finasteride</span>''' 
***'''<span style="color:#ff0000">Absolute risk reduction: 6%</span>''' (18.4% finasteride vs. 24.4% placebo)
** '''<span style="color:#ff0000">Significant increase biopsy Gleason score 7-10 cancers in finasteride group</span>'''
***'''<span style="color:#ff0000">Absolute risk increase: 15%</span> among those undergoing biopsy''' (37% finasteride vs. 22% placebo)
** '''Apparent increase in high-grade cancers with the use of 5-ARIs does not influence cancer-specific survival''' [https://pubmed.ncbi.nlm.nih.gov/30673548/ Goodman, Phyllis J., et al.] "Long-term effects of finasteride on prostate cancer mortality." New England Journal of Medicine 380.4 (2019): 393-394.
* [https://www.nejm.org/doi/full/10.1056/NEJMoa030660 Thompson, Ian M., et al.] "The influence of finasteride on the development of prostate cancer." New England journal of medicine 349.3 (2003): 215-224.

=== <span style="color:#ff00ff">REDUCE (NEJM 2010)</span> ===
* '''<span style="color:#ff0000">Objective: determine whether a 5-ARI could reduce the risk of prostate cancer</span>'''
* '''<span style="color:#ff0000">Population: 8,231 men aged 50-75 with a negative prior biopsy within 6 months of enrollment baseline PSA 2.5-10, prostate volume ≤80cc</span>''' 
* '''<span style="color:#ff0000">Randomized to dutasteride vs. placebo daily</span>'''
* '''<span style="color:#ff0000">Primary end point: prevalence of cancer on study-mandated 10-core prostate biopsies performed at 2 and 4 years after randomization (different from PCPT where biopsy was not mandated)</span>'''
* '''<span style="color:#ff0000">Results:</span>''' 
**6.726 (82.6%) underwent at least one biopsy
** <span style="color:#ff0000">'''Significantly reduced risk of incident prostate cancer with dutasteride''' </span>
***'''Absolute risk reduction: 5%''' (19.9% dutasteride vs. 25.1% placebo)
** '''No difference in Gleason 7-10 cancers throughout the study, however, increased risk of Gleason 8-10 cancers during years 3 and 4 in dutasteride arm[https://www.nejm.org/doi/full/10.1056/NEJMoa0908127#]'''
* [https://www.nejm.org/doi/full/10.1056/NEJMoa0908127 Andriole, Gerald L., et al.] "Effect of dutasteride on the risk of prostate cancer." New England Journal of Medicine 362.13 (2010): 1192-1202.