Combination medical therapy with alpha blocker plus finasteride reduces clinical progression of BPH more than either drug alone, and combination or finasteride alone reduces the risk of acute urinary retention or needing surgery (MTOPS)
This landmark trial randomsied 3047 mean to either doxazosin alpha blocker alone 1mg start dose up to either 4 mg or 8 mg if tolerated or finasteride 5 mg daily or combination therapy or placebo and follow up was 4.5 years. Overall clinical progression risk (AUA score increase ≥4, acute urinary retention) was significantly reduced by combination therapy than either alone (66% reduction v 34% finasteride, 39% doxazosin) and combination therapy and finasteride significantly reduced the risk of need for invasive surgery and urinary retention. The patients in this study were median age 63, median AUA score 17, mean prostate volume 36 ml, mean flow rate 10.5 ml/sec, mean PVR 68, mean PSA 2.4 ng/ml, mean creatinine 1.1 mg/dl, no previous prostate surgery. The rate of drug discontinuation was 27% doxazosin, 24% finasteride, 18% on combination. Adverse effects were – doxazosin, dizziness, postural hypotension, asthenia (**alpha blocker therapy in hypertensive patients had a higher risk of cardiac failure, angina, stroke, so should be prescribed in this group in consultation with a cardiologist) and finasteride, erectile dysfunction, decreased libido, abnormal ejaculation (4 men had breast cancer). The individual results were:
- Acute urinary retention risk reduced – combination 81%, finasteride 68% (not doxazosin)
- Invasive surgery risk reduced – combination 67%, finasteride 64% (not doxazosin)
- Symptoms progression (increase in AUA score ≥4 points) – risk reduced by 64% combination, 45% doxazosin, 30% finasteride
- Symptom score reduced – combination 7.4 points, finasteride 5.6, doxazosin 6.6, placebo 4.9
- Flow rate reduced – combination 5.1 ml/sec, finasteride 3.2, doxazosin 4.0
- PSA – reduced by 50% combination and finasteride, increased by 15% placebo, 13% doxazosin
- Prostate volume – combination and finasteride reduced by 20%, placebo and doxazosin increased by 24%.
Also of interest was in the placebo group (n=737) at 4 years the cumulative incidence of clinical progression was 17%, urinary retention 2%, urinary infection <1%, invasive surgery 5%, increase in symptom score ≥4 14%.