Efficacy and safety of tolterodine extended-release in men with overactive bladder symptoms treated with an α-blocker: effect of baseline prostate-specific antigen concentration.

Objective: To determine whether the efficacy and safety of a combination of tolterodine extended-release (ER) plus α-blocker treatment varies with high or low levels of serum prostate-specific antigen (PSA) in men who have persistent overactive bladder (OAB) symptoms after any α-blocker monotherapy.

Methods: Men aged ≥ 40 years were eligible if they reported ≥ 8 micturitions/24 h, including ≥ 1 urgency episode/24 h with or without urgency urinary incontinence (UUI), and at least some moderate bladder-related problems at baseline despite receiving treatment with an α-blocker for ≥ 1 month. Exclusion criteria included a postvoid residual urine volume (PVR) of ≥ 200 mL and history of acute urinary retention requiring catheterization. Subjects were randomly assigned to tolterodine-ER 4 mg or placebo for 12 weeks; all subjects continued their α-blocker treatment throughout the study. Subjects completed 5-day bladder diaries at baseline and week 12, in which they recorded all micturitions and rated the sensation associated with each micturition using the 5-point Urinary Sensation Scale (USS). For this post hoc analysis, efficacy, safety, and tolerability data were stratified by the study median PSA concentration at baseline (1.41 ng/mL).

Results: In the tolterodine-ER +α-blocker and placebo +α-blocker groups, 160 and 159 men, respectively, had PSA levels of <1.41 ng/mL, and 166 and 160 men, respectively, had PSA levels of ≥ 1.41 ng/mL. Men with higher PSA levels were slightly older and had higher PVR at baseline compared with men with lower PSA levels. At week 12, improvements in daytime micturitions, 24-h urgency episodes, and daytime urgency episodes were significantly greater with tolterodine-ER +α-blocker vs placebo +α-blocker both in men with PSA levels of ≥ 1.41 ng/mL and those with PSA levels of < 1.41 ng/mL (P < 0.05). Among men with PSA levels of < 1.41 ng/mL, improvements in 24-h micturitions and frequency-urgency sum (sum of USS ratings for all micturitions) were also significantly greater with tolterodine-ER +α-blocker vs placebo +α-blocker (P < 0.05). There were no significant treatment differences in change in UUI episodes in either PSA group (although only 19% of subjects reported UUI at baseline), nor in nocturnal micturitions or nocturnal urgency episodes. Among men with PSA levels of ≥ 1.41 ng/mL, there was a statistically significant increase in PVR (P = 0.036) and decrease in maximum urinary flow rate (Q(max); P = 0.038) with tolterodine-ER +α-blocker vs placebo +α-blocker; these changes were not considered clinically meaningful. There were no treatment differences for changes in PVR or Q(max) among men with PSA levels of < 1.41 ng/mL. One subject receiving tolterodine-ER +α-blocker (PSA concentration of ≥ 1.41 ng/mL) and two subjects receiving placebo +α-blocker (one each in the PSA concentration subgroups of ≥ 1.41 ng/mL and < 1.41 ng/mL) had acute urinary retention requiring catheterization.

Conclusions: In a 12-week study, the addition of tolterodine-ER to α-blocker therapy improved key OAB symptoms and appeared to be well tolerated compared with placebo +α-blocker in men with persistent OAB symptoms, regardless of subjects' prostate size as judged by serum PSA concentration.