The 5-alpha-reductase inhibitors, also known as 5-ARIs or dihydrotestosterone (DHT) blockers, are generally used for the long-term treatment of benign prostate hyperplasia (BPH). However, according to a recent study, these drugs reduce serum prostate-specific antigen (PSA) levels by half, which can lead to an underestimation of a possible risk of prostate cancer.
In the population-based cohort study published in 2019, data from a total of 80,875 men with prostate cancer diagnosed between 2001 and 2015 were examined. The research team focused on the question of whether the use of 5-ARI before a diagnosis could delay the time of diagnosis and increase the risk of higher-grade prostate cancer (PCa).
The time from the first elevated PSA level to the diagnosis of "prostate cancer" was actually significantly increased in the median of those men who had previously received 5-ARIs for the treatment of BPH compared to those without 5-ARIs (3.6 years versus 1.4 years; p < 0.001).
In addition, the median PSA level was significantly elevated in the 5-ARI patients at the time of prostate biopsy compared to men who had not received such inhibitors (13.5 ng/mL vs. 6.4 ng/mL; p < 0.001).
In addition, the suspicion that men with a history of 5-ARI were at higher risk for more advanced tumors at initial diagnosis than those without 5-ARI was confirmed (25.2% Gleason ≥ 8 vs. 17% Gleason ≥ 8; p < 0.001 and stage ≥ T3: 4.7% vs. 2.9%; p < 0.001). In addition, more than twice as many patients with 5-ARI had already metastasized (6.7% vs. 2.9%; p < 0.001).
Overall, men following 5-ARI showed a higher risk of both cancer-specific (HR = 1.39; 95% CI: 1.27-1.52; p < 0.001) and all-cause mortality (HR = 1.10; 95% CI: 1.05-1.15; p < 0.001).
The results of this cohort study show that the use of 5-ARI in patients with BPH can adversely affect or delay the outcome of prostate cancer screening and, in case of doubt, also a cancer diagnosis.
As a consequence, this results in delayed diagnosis at a more advanced tumor stage and a related worse prognosis for the men affected.
It is therefore particularly important to raise awareness of the fact that men with BPH who are offered therapy with 5-alpha-reductase inhibitors have a higher risk of PSA value suppression. These patients should, therefore, be monitored more closely in preventive assessments, the study authors said. So far, however, there are no recommendations or protocols on how to proceed in order to provide optimal care for men undergoing 5-ARI therapy.
Source:
Parsons JK et al., JAMA Intern Med 2019; doi:10.1001/jamainternmed.2019.0280