medwireNews: Use of 5α-reductase inhibitors (5-ARIs) is not associated with an increased risk for prostate cancer mortality (PCM), and long-term use may indeed reduce the risk, a Swedish population-based study has found.
“The results suggest the safety of 5-ARI treatment concerning PCM,” comment the investigators, adding that the previously reported “increased grade and stage of [prostate cancer] at diagnosis” for men treated with 5-ARIs does not appear to adversely impact PCM.
“However, it is still unclear if 5-ARIs inherently suppress or slow the growth of [prostate cancer], or if the survival difference is caused by increased and more sensitive testing,” they continue.
The researchers collated data from multiple Swedish registries – such as the Stockholm PSA and Biopsy Register, National Prostate Cancer Register, Prescribed Drug Register, and Swedish Death Register – and identified 349,152 men aged at least 40 years without a prior prostate cancer diagnosis who underwent prostate-specific antigen (PSA) testing during January 2007–December 2017. Of these, 26,190 were classified as 5-ARI users (median use, 4.5 years) as they had filled two or more new prescriptions for finasteride or dutasteride during the study period.
Over a median follow-up of 8.2 years, 0.4% of 5-ARI users and 4.2% of nonusers received a diagnosis of prostate cancer. In all, 10.2% of the participants died, and 2.4% of the deaths were attributed to prostate cancer.
Multivariable analysis adjusting for age, family history of prostate cancer, comorbidities, and other confounders showed a time-dependent association between use of 5-ARIs and a reduced risk for PCM. For instance, 0.1–2.0 years of use was associated with a nonsignificant 11% reduced risk for PCM versus no use, while the risk was reduced by a significant 49% and 56% with 6.0–8.0 years and more than 8.0 years of use, respectively.
By contrast, there was no significant difference between 5-ARI users and nonusers with regard to all-cause mortality risk irrespective of the level of exposure.
The results were similar in a sensitivity analysis using a “model with time-dependent 5-ARI exposure, which was based on treatment episodes that were updated at each drug [prescription],” report Lars Björnebo and colleagues, from Karolinska Institutet in Solna, Sweden, in JAMA Oncology.
They also found that “men receiving treatment with 5-ARI had significantly higher diagnostic activity” than nonusers, with more PSA tests and prostate biopsies per year, at medians of 0.63 versus 0.33 and 0.22 versus 0.12, respectively.
The authors summarize that “[c]ombined evidence from this study, randomized trials, and other observational studies suggest that treatment with 5-ARI does not increase the risk of prostate cancer and may decrease the risk of dying of [prostate cancer].”
And they conclude: “Future research may extend this work by separating the inherent effects on PCM of 5-ARI from differences in diagnostic activity with an interventional design, thereby reducing biases that affect observational studies.”
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