Assessment of Conservative Combination Therapies for Active and Stable Peyronie's Disease: A Systematic Review and Meta-analysis

Context: In patients with Peyronie's disease (PD), oral, injected, or topical agents provide limited efficacy. In this setting, combination of two or more conservative treatments may improve symptoms further. Objective: To explore the effects of available conservative combination therapies for active and stable PD through a systematic review and meta-analysis. Evidence acquisition: We searched multiple databases and sources of gray literature until June 2021. We included randomized or observational comparative studies assessing any conservative combination therapies for PD. We undertook a random-effect meta-analysis when at least two studies employed the same treatment modality (PROSPERO: CRD42021224517). Evidence synthesis: Overall, 13 studies on active PD and ten on stable PD (1962 participants) were included. Most included studies raised methodological concerns. In patients with active or stable PD, the available evidence is inconclusive to support the use of any combination treatment modality, such as intralesional verapamil injections, antioxidants, and other oral, injected, or topical agents. Based on data availability, we performed a meta-analysis to compare the effect of collagenase Clostridium histolyticum (CCH) plus adjunctive mechanical therapies (penile traction or vacuum pump) versus CCH monotherapy on penile curvature and length in patients with stable PD. CCH and adjunctive mechanical therapies resulted in an additional decrease of 0.3° in penile curvature (95% confidence interval [CI]: −3.97 to 4.49, I2 = 0%) and in an increase of 0.5 cm in penile length (95% CI: −0.32 to 1.4, I2 = 70%) compared with CCH monotherapy. Conclusions: The available combination treatment modalities, including the addition of adjunctive mechanical therapies to CCH, do not improve symptoms further compared with monotherapy and should not be implemented in patients with active or stable PD. Further high-quality randomized trials combining only recommended treatments are mandatory. Patient summary: Despite the interest in and optimism for combination treatment modalities, the road to an effective conservative therapy for Peyronie's disease still seems long.