Study FDC114615: Comparative efficacy of DuodartTM plus lifestyle advice versus watchful waiting plus lifestyle advice with step-up therapy to tamsulosin in the management of treatment naïve men with moderately symptomatic benign prostatic hyperplasia and prostate enlargement.

*Standard care* for men with symptoms of BPH at risk of progression has
developed into a cascade that escalates from watchful waiting through single or
multiple drugs and finally to surgery if lower urinary tract symptoms are
severe or bothersome enough to warrant intervention. The most widely used
strategy in urological practice is the system of sequential step-up therapy
that forms the essence of standard care. In this system, clinicians and
patients decide between them what treatment, if any, shall be initiated. If it
is effective and well tolerated it is continued often for long periods. If the
therapy is not well tolerated, another can be instituted, or the patient may be
referred for surgery. In the case of a failure of efficacy, combination medical
therapy can be tried, or the patient referred for surgery. Transurethral
resection of the prostate (TURP) is the most commonly used surgical
intervention. Although TURP reduces lower urinary tract symptoms (LUTS) to a
much greater extent than medical therapy, it is associated with irreversible
side effects, most notably urinary incontinence and retrograde ejaculation, and
so current practice is typically to utilise medical therapy prior to a surgical
referral.
In the only published study on men with LUTS where standard care (watchful
waiting followed by escalation) was used, exposure to standard care did not
result in an improvement in LUTS compared with baseline at 3, 6 or 12 month
evaluation points, although escalation to active therapy only occurred in a
minority of subjects. Therefore, it is possible to conclude that standard care
when offered to that particular patient population was ineffective in bringing
about a measurable improvement in the health status, although those that had
intervention had some benefit. This also questions the rationale of *watchful
waiting*, especially in men whose baseline parameters, most notably prostate
volume, PSA, IPSS and bother scores, place them in a category of being at a
heightened risk of disease progression due to worsening of symptoms, acute
urinary retention (AUR) or BPH-related surgery.
In men with a symptomatic BPH (moderate to severe symptoms), i.e. a baseline
prostate volume of *30 cc and a PSA of *1.5 ng/mL, we now have Level 1b
evidence that in long-term therapy, a combination of dutasteride and tamsulosin
results in a greater degree of symptom reduction and a lower risk of clinical
progression when compared with using either as monotherapy.

Primary: Effectivity. Secundary: Effectivity (questionnaires, progression,
surgery), safety and tolerability.

Multicenter randomized open parallel group phase IV study.
Randomisation (1:1) to treatment with:
1. Watchful waiting plus leefadviezen, zo nodig gevolgd door behandeling met
tamsulosine.
2. Combodart eenmaal per dag plus leefadviezen.
Treatment duration 2 years.
Approx 760 patients randomized.

Watchful waiting or Combodart, both combined with lifestyle advice.

Burden: 11 visits in 2 years. Duration 1-2 h.
Physical examination (incl. internal prostate examination) 3x. Echo prostate
and post-void residu 1x.
Blood tests 3x approx.. 10 ml/visit. Qustionnaires (IPSS, BII, patient
perception questionnaire) all visits.
Lifestyle advice.