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.