The effects of dutasteride or tamsulosin alone and in combination on storage and voiding symptoms in men with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH): 4-year data from the Combination of Avodart and Tamsulosin (CombAT) study

Study Type - Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Long-term treatment with combination therapy (dutasteride plus tamsulosin) is significantly superior to tamsulosin but not dutasteride at reducing the relative risk of AUR or BPH-related surgery. Furthermore, combination therapy is significantly superior to both monotherapies at reducing the relative risk of BPH clinical progression, and provides significantly greater reductions in IPSS. In addition, combination therapy significantly improves patient-reported, disease specific QoL and treatment satisfaction compared with either monotherapy. Two-year results from the CombAT study showed that combination therapy was more effective than either monotherapy in controlling both storage and voiding symptoms, irrespective of baseline prostate volume (for men with prostate volume ≥30 cc). This post-hoc two-year analysis also showed that treatment with dutasteride not only improved voiding symptoms, as would be expected from its effects on prostate volume, but was also as effective as the α-blocker tamsulosin in the control of storage symptoms. Objective: To assess the effects of combined therapy with dutasteride and tamsulosin on voiding and storage symptoms compared with those of dutasteride or tamsulosin alone, using 4-year data from the Combination of Avodart and Tamsulosin (CombAT) study. Patients and methods: Men (n = 4844) aged ≥50 years with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH), a prostate volume of ≥30 mL, and a serum prostate-specific antigen level of 1.5-10 ng/mL. CombAT was a multicentre, double-blind, parallel-group study. Oral dutasteride (0.5 mg) or tamsulosin (0.4 mg) alone or in combination was taken daily for 4 years. Mean changes from baseline in storage and voiding symptoms at 4 years were assessed using subscales of the International Prostate Symptom Score. Results: At 4 years, the mean reduction in the storage subscore was significantly greater in the combined therapy group vs the dutasteride (adjusted mean difference -0.43) and tamsulosin (adjusted mean difference -0.96) monotherapy groups (P < 0.001). Also at 4 years, the mean reduction in the voiding subscore was significantly greater in the combined therapy group vs the dutasteride (adjusted mean difference -0.51) and tamsulosin (adjusted mean difference -1.60) monotherapy groups (P < 0.001). The improvement in the storage subscore with combined therapy was significantly better (P < 0.001) than dutasteride and tamsulosin from 3 months and 12 months, respectively. Similarly, the improvement in the voiding subscore with combined therapy was significantly better than dutasteride (P < 0.001) and tamsulosin (P ≤ 0.006) from 3 months and 6 months, respectively. Improvements in the storage and voiding symptom subscores with combined therapy were achieved irrespective of prostate volume, although in men with the highest baseline prostate volumes (≥58 mL), combined therapy was not better than dutasteride. Conclusions: In men with a prostate volume of ≥30 mL, combined therapy with dutasteride plus tamsulosin provided better long-term (up to 4 years) control of both storage and voiding LUTS compared with tamsulosin monotherapy. Combined therapy was better than dutasteride monotherapy in men with prostate volumes of ≥30 to <58 mL, but not in men with a prostate volume of ≥58 mL.