Peyronie's disease (PD) is a superficial fibrosing condition of the penis characterized by plaque development in the tunica albuginea. PD often presents with a constellation of penile curvature, pain, and erectile dysfunction (ED).¹ The exact etiology of the Peyronie's plaque is not completely understood; however, it is thought to be secondary to an excessive healing response to sexual trauma in genetically susceptible individuals. Collagenase Clostridium histolyticum (CCH; Xiaflex^®, Endo Pharmaceuticals, Malvern, Pennsylvania) is an injectable therapeutic agent that selectively degrades collagen type I and III and thereby degrades the tunical fibrotic plaque (fig. 1).¹ It is suggested that once the plaque is weakened, the patient undergoes penile modeling that acts in synergy with the enzymatic process to reduce curvature and potentially increase penile length. CCH is the first and only intralesional agent approved by the U.S. Food and Drug Administration (FDA) to treat PD.²

Figure 1. CCH mechanism of action.

Evidence as to the safety and efficacy of CCH in the treatment of PD has been documented in the IMPRESS (Investigation of Maximal Peyronie’s Reduction Efficacy and Safety Studies) trials, 2 double-blinded, placebo-controlled phase III studies which included 836 patients at 64 sites in the United States and Australia.³ The IMPRESS trials did not include PD patients who presented with a ventral penile plaque (fig. 2) or men in the acute phase of PD (≤12 months).³ FDA approval of intralesional CCH does not include use for those men with atypical curvatures (ventral or hourglass deformities with curvatures <30°).² And yet, ventral curvatures represent a significant subgroup of PD cases, with approximately 9% of all plaques located on the ventral aspect of the penis.⁴ Available evidence suggests that PD patients with ventral curvatures treated with intralesional CCH experience similar safety and efficacy outcomes compared to dorsal or dorsal-lateral plaques.

Figure 2. Patients with ventral penile plaque and curvature.

A prospective cohort study published in 2019 included 228 patients treated with CCH for PD.⁵ Subjects in this study included those with atypical curvatures with 83%, 50% and 11% of the sample displaying some degree of dorsal, lateral and ventral angulation, respectively. Analysis of outcome measures by curvature group revealed more substantial improvements in the ventral and lateral groups than the dorsal group. While the dorsal curvature group experienced a 25% reduction in curvature, the ventral and lateral groups experienced improvements of 49% and 38%, respectively. The ventral and lateral curvature groups were also more likely to experience a greater degree (≥50%, ≥75% and ≥90%) of curvature improvement than those within the dorsal group. Limitations to this study included a relatively low census of ventral-curvature patients, limited followup duration and biases associated with an as-treated model. Furthermore, a retrospective study published in 2017 included 53 patients with ventral curvature.⁶ Patients received 3 CCH injections of 0.9 mg intralesionally at 4-week intervals in addition to modeling, stretching exercises, and vacuum therapy. Median penile curvature in the ventral curvature group was 40.0° with an interquartile range of 30° to 45°. Reductions in penile curvature were reported in interquartile range, with the middle 50% of patients experiencing between −20 to −10 reduction in curvature with a median of −20, which was statistically significant. No serious adverse events were reported. This study was also limited by a relatively small sample size. Notably, both of these studies reported that common adverse events included those typically observed with treatment with CCH for routine dorsal or dorsolateral curvatures, including local penile swelling, pain, hematoma and ecchymosis.

During the acute phase PD (defined as presence of penile pain and progression of curvature and duration of PD no longer than 12 months), patients usually experience significant psychological distress due to lack of an effective treatment during this period. Therefore, several studies have investigated the use of CCH injection during the acute phase PD. Nguyen et al conducted a study to specifically investigate the efficacy and safety of CCH injection in treating acute phase PD compared with stable disease.⁷ An analysis of 162 patients (22% with acute phase PD and 78% with stable phase PD) showed that CCH intralesional injections resulted in similar improvement in penile curvature in both groups (16.7° in acute phase vs 15.6° in stable phase; p=0.654). Furthermore, there were no statistically significant differences in frequency of treatment-related adverse events between the acute phase (4 patients, 11%) and the stable phase (12, 10%; p=0.778). This finding was subsequently reported in other studies.^8–10 Moreover, Cocci et al investigated the effect of a single injection of CCH in 72 patients with acute PD with mean penile curvature of 41.1° (±12.2°).⁸ Results showed that after 3 months there was mean improvement of penile curvature of 19.3° (±8.4; p <0.0001). There were also mild mean improvements of International Index of Erectile Function score of 1.1 (±0.9; p=0.02) and Peyronie’s Disease Questionnaire and in its subscores (psychological symptoms, penile pain and bother disease). These results suggest that CCH injection is safe and efficacious in the treatment of acute phase PD and perhaps reduces the psychological bother associated with treatment delays. However, because of the retrospective nature of these studies, further prospective studies are warranted to validate these findings.

In conclusion, intralesional CCH can provide benefit to PD men with ventral curvatures, and in men with PD who present in the acute phase.