Combined therapy with dutasteride and tamsulosin is better than monotherapy in reducing the risk of clinical progression of BPH in men with moderate-severe symptoms.

Almost 5,000 men over 50 years old with clinical BPH, IPSS more than or equal to 12 (i.e. at least moderately severe symptoms),

PSA 1.5 - 10 ng/ml and prostate volume >30cm3 were enrolled in the Combat study.

Patients were randomised to receive either tamsulosin, dutasteride or a combination of both, in this double blind, parallel group study. They were followed up for four years.

Several endpoints were examined by the study. First, time taken to progress to either acute urinary retention (AUR) or BPH-related surgery. Here, combination therapy was significantly better than tamsulosin monotherapy in reducing risk (p<0.0001), but not significantly better than dutasteride alone (p=0.18).

Combination therapy reduced the relative risk of AUR or BPH-related surgery by 65.8% compared with tamsulosin and by 19.6% compared with dutasteride.

The risk of these events occurring over the four years of the study was 11.9% in the tamsulosin arm, versus 5.2% for dutasteride and 4.2% for combination therapy.

Time to first BPH clinical progression was significantly different in favour of combination therapy compared with either monotherapy (p<0.001 for both comparisons). Combination therapy reduced the relative risk of BPH clinical progression by 44.1% compared with tamsulosin and 31.2% compared with dutasteride.

Symptom deterioration was the most common clinical progression event in each treatment group. Time to first symptom deterioration was significantly better for combination therapy compared with tamsulosin and dutasteride (p<0.001 for both comparisons). Combination therapy reduced the relative risk of symptom deterioriation of IPSS more than or equal to 4 points by 41.3% versus tamsulosin and 35.2% versus dutasteride.

In terms of symptom control, dutasteride was superior to tamsulosin monotherapy over the four years of the study. While tamsulosin was superior initially (due to quicker onset of action), after 15 months dutasteride became superior in IPSS reduction, with this difference increasing as the study progressed. Combination therapy gave significantly greater benefit than either monotherapy.

How should this important study affect prescribing for BPH in primary care? It shows that patients need full evaluation in terms of risk factors for progression to AUR or surgery, and

5-alpha reductase inhibitors considered for patients with LUTS deemed to be high risk.

It also demonstrates that while alpha blockers are better for short-term symptom relief in these patients, dutasteride is clearly superior in the long term, whether as monotherapy or in combination.

This would seem to give some justification for the management strategy of initiating combination therapy for patients with moderate to severe LUTS considered at risk of progression, and the subsequent trial of withdrawal of the alpha blocker at 12-18 months, accepting the slightly lower efficacy of 5-alpha reductase inhibitor monotherapy in terms of symptom control.

This approach may be more acceptable to patients increasingly concerned with polypharmacy and associated side-effects.