SPECIAL ISSUE - AGOlive Event: Prostate (Part1): Prostate cancer prevention with 5-alpha reductase inhibitors: is this a reasoned practice? Concepts and controversies
M. Falsaperla, G. Bonvissuto
Vol.6 (2021), issue 2, pag. 82 - 90
SPECIAL ISSUE - AGOlive Event: Prostate (Part1): Prostate cancer prevention with 5-alpha reductase inhibitors: is this a reasoned practice? Concepts and controversies
M. Falsaperla, G. Bonvissuto
Vol.6 (2021), issue 2, pag. 82 - 90
| Received | 23/08/2021 |
| Accepted | 1/09/2021 |
| Published | 07/09/2021 |
| Review by | Single-blind |
| DOI | https://doi.org/10.48253/AGO14 |
ABSTRACT
Prostate cancer prevention provides an alternative to early detection and the use of the 5-alpha reductase inhibitors to prevent prostate cancer has been investigated. In the Prostate Cancer Prevention Trial (PCPT), nasteride reduced the relative risk (RR) of prostate cancer by 24.8% compared with placebo, but its use was also as- sociated with a 26.9% increase in the risk of developing high-grade cancers. Similarly, in the Reduction by Dutasteride of Prostate Can- cer Events (REDUCE) trial, dutasteride was also found to reduce the RR of prostate cancer with an increase in the detection of high- grade cancers. Following this in 2011, the US FDA announced a label change citing the increased risk of high-grade prostate cancer in patients taking 5-ARIs. The American Society of Clinical Oncolo- gy and the AUA have updated the guidelines on the use of 5-ARIs discouraging non-FDA-approved use for cancer chemoprevention. Recent long-term follow-up of patients in the Prostate Cancer Pre- vention Trial demonstrated that after 18 years of follow-up, there remained a 30% reduction in the RR of low-grade prostate cancer but no signi cant decrease in overall mortality.
It is possible that low-grade tumors may have a different etiology than high-grade and the effects of 5-ARIs may differ based on tu- mor characteristics. The underlying mechanism of the differential effects of 5-ARIs on high-grade and low-grade tumors are not clear- ly understood, one may conclude that low-grade prostate cancer require classical androgenic stimulation whilst we hypothesize that progression to high-grade tumors may at least in some cases not require this stimulus.
By means of pharmacobiology studies, it was possible to under- stand that dihydrotestosterone is not an indispensable hormone of the metabolic pathway of prostate cancer cells.
Prostate cancer cells, even in the presence of low levels of dihy- drotestosterone or even in its absence, are able to continue their metabolic activities and also to progress, exploiting the use of other steroid hormones such as testosterone or dehydroepiandroster- one, or even by non-hormonal stimuli such as interleukin or other biochemical growth factors.