Discussion
Our real-life data concerning current pharmacotherapy for benign prostate enlargement (BPE) shows that ARAs monotherapy remains as the most frequent therapeutic option utilized in more than one-third of patients. It is in line with the survey performed among Polish urologists, showing that ARAs in monotherapy was the first line option for patients with and even without BPE [13]. When comparing the prescribed medication for non-neurogenic LUTS with the data coming from PolSenior study [15], performed in years 2007 – 2012, one may see that the prescription of ARAs in monotherapy has declined from 64.7 to 25.6%, during last years, possibly as a consequence of later guidelines from 2010. In parallel, during this period of time there was an increase in the utilisation of ARA+5αRI combined therapy from 21.9% to 30.9% and most spectacularly the use of MRAs (in the combined therapy) from 1.7 to 23.6%. The increase in the utilization of MRAs, revealed by our observation, is in line with the treatment option accepted by 83.7% of Polish urologists concerning MRAs use for the management of storage LUTS [13]. While the most recently introduced drug – mirabegron is currently rarely used (1.4% of overall study population and 2.4% of those with storage symptoms), probably due to the lack of reimbursement from Polish National Health Fund. Of note, as much as 54.5% of patients with storage symptoms were treated neither with MRAs nor with β3-adrenergic receptors agonists, despite the EAU recommendations.
Similarly to Poland, the ARAs monotherapy is the most frequently utilized medication for BOO in the USA, yet slowly decreasing during the last decade from 74.6% in 2006 to 68.7% in 2014 in favour of monotherapy with 5αRI [16]. BOO medication in the USA was characterized by more profound, than in Poland (based on our data), underutilization of MRAs. Only 3.7% of the USA cohort with BPH/LUTS were prescribed with MRAs (5.7% of those receiving other BOO medication) with no significant increase in the study period (2006-2014).
A different landscape is presented by a recent MERCURE study from Spain [17], that analysed the compliance with the EAU 2013 recommendations in the management of LUTS in men. In this study, treatment with ARAs in monotherapy and ARAs with MRAs was almost equally frequent (37.5 vs 37.2%, respectively).
Having in mind the recommended individualization of pharmacotherapy for non-neurogenic LUTS, that take into account not only the severity, prostate volume, structure / dominance of certain symptoms, but also co-morbidities as well as patients’ expectations and preferences, we analysed how storage symptoms (urinary urgency, frequency and nocturia) affects the prescription of 5αRI and MRAs. We have demonstrated that decisions concerning pharmacotherapy with MRAs was affected mostly by the occurrence of urinary urgency and urinary frequency, but not nocturia, among the storage symptoms. In addition MRAs were more frequently prescribed in younger adults (< 65 years old). While the decision concerning the use of 5αRI was mostly affected by severity of LUTS, older age and education level.
The more frequent choice of 5αRI in older men is potentially explainable by a benefit from reducing the risk of prostate cancer during long-term with these drugs [18], while bearing the risk of decrease in libido, ejaculation disorders and painful enlargement of the breast [19]. However, it is hard to say whether it reflects patients’ preferences or the knowledge of the physicians.
The relatively high costs of MRAs therapy in Poland probably explain the more frequent use of these drugs in triple, rather than double schedule, and more prevalent utilization of cheaper tolterodine rather than solifenacin (in 20.2 and 9.0% of MRAs users, respectively). In line with this statement is the low utilization of mirabegron (more expensive than MRAs), the only currently available β3-adrenoceptors agonist, in patients with storage symptoms. Our data indirectly demonstrates how per capita income modifies the application of the EAU recommendations in European societies.
Study limitations are related to the methodology. The survey was focused mostly of the current clinical presentation of storage symptoms, and not those preceding the initiation of pharmacotherapy. The survey did not collect the data concerning the changes in medication during the therapy. We cannot exclude some overrepresentation of patients with more severe symptoms, potentially, more frequently utilizing medical services. The generalization of the data is restricted to Polish population due to the effect of drug reimbursement policy by the national health system.
In conclusion: urinary urgency and frequency are associated with increased utilization of MRAs in men with BPE in daily clinical practice. The attitude of Polish urologists toward management of persistent storage symptoms in BPE patients is in line with EAU guidelines.