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Published on: March 6, 2018
5α-Reductase Inhibitors and Risk of Prostate Cancer Death
Tiago Bonde Miranda1, Hans Garmo2, Par Stattin3
1Department of Urology, Ryhov Hospital, Jonkoping, Sweden.
Purpose:
5α-Reductase inhibitors reduced the risk of prostate cancer in 25% in 2 randomized trials but increased the risk of Gleason 8-10 at biopsy. One explanation is that 5α-reductase inhibitors induce morphological changes in prostate cancer cells similar to higher Gleason grades but without its adverse biology. We compared risk of prostate cancer death between men on 5α-reductase inhibitors and men not on 5α-reductase inhibitors before prostate cancer diagnosis in each Gleason Grade Group.
Materials And Methods:
Prostate Cancer data Base Sweden consists of linkages between the National Prostate Cancer Register, the Prescribed Drug Registry and the Cause of Death Registry. Of 89,227 men diagnosed with prostate cancer between July 2007 and December 2016, 5,816 had been on 5α-reductase inhibitors for more than 180 days before the date of diagnosis. Followup ended in December 2018. A Cox proportional hazard model was used to assess hazard ratio for prostate cancer death. Adjustments for age, comorbidity, education and curative treatment were made. Men with high risk cancer were stratified according to Gleason Grade Group.
Results:
In men with high risk cancer the risk of prostate cancer death was similar among 5α-reductase inhibitor users and nonusers, with Gleason Grade Group 1 HR 1.02 (95% CI 0.53-1.95), Gleason Grade Group 2 HR 1.04 (95% CI 0.65-1.69), Gleason Grade Group 3 HR 1.27 (95% CI 0.89-1.80), Gleason Grade Group 4 HR 0.95 (95% CI 0.76-1.18) and Gleason Grade Group 5 HR 0.99 (95% CI 0.83-1.19), for 5α-reductase inhibitor users vs nonusers.
Conclusions:
We found no evidence that 5α-reductase inhibitors affect Gleason grading as no difference in mortality was observed among 5α-reductase inhibitor users and nonusers in each Gleason group.
Insights
5α-Reductase inhibitors did not increase prostate cancer death risk across Gleason Grade Groups. This study found no evidence that these inhibitors affect Gleason grading, as mortality rates were similar between users and non-users.
Area of Science:
- Oncology
- Pharmacology
- Urology
Background:
- 5α-Reductase inhibitors (5ARIs) are associated with reduced prostate cancer risk but potentially increased high-grade disease.
- A hypothesis suggests 5ARIs induce morphological changes mimicking higher Gleason grades without altering cancer biology.
- Investigating the impact of 5ARIs on prostate cancer mortality across different Gleason Grade Groups is crucial.
Purpose of the Study:
- To compare prostate cancer death risk between 5ARI users and non-users stratified by Gleason Grade Group.
- To determine if 5ARIs influence the actual aggressiveness or mortality of prostate cancer.
- To address the discrepancy between reduced cancer incidence and potential increased high-grade diagnosis.
Main Methods:
- Utilized the Prostate Cancer data Base Sweden, linking national registers for prostate cancer, prescribed drugs, and causes of death.
- Analyzed data from 89,227 men diagnosed with prostate cancer between 2007 and 2016, with 5,816 on 5ARIs for over 180 days pre-diagnosis.
- Employed Cox proportional hazard models, adjusting for clinical factors, and stratified high-risk cases by Gleason Grade Group.
Main Results:
- No significant difference in prostate cancer death risk was observed between 5ARI users and non-users across all Gleason Grade Groups (Gleason Grade Group 1-5).
- Hazard ratios for prostate cancer death were consistently close to 1.0 across all Gleason Grade Groups, indicating similar mortality.
- Specific HRs for Gleason Grade Groups 1-5 were: 1.02, 1.04, 1.27, 0.95, and 0.99, respectively, for 5ARI users versus non-users.
Conclusions:
- 5α-Reductase inhibitors do not appear to affect the mortality risk associated with prostate cancer across different Gleason Grade Groups.
- The findings suggest that observed increases in high-grade biopsies in previous studies may not translate to increased prostate cancer death.
- There is no evidence from this study to support that 5ARIs alter the underlying biology or lethality of prostate cancer.
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