Luke Witherspoon, MSc, MB, MD, was one of the recipients of the 2024 Urology Care Foundation™ Research Scholar Awards. These awards provide $40,000 annually for mentored research training for clinical and postdoctoral fellows or early-career faculty. The Sexual Medicine Society of North America sponsored Dr Witherspoon’s award.

Clinical Problem to Be Addressed

Peyronie’s disease (PD) is a collagen-based fibrosing disorder of the penis characterized by fibrous inelastic plaque formation of the tunica albuginea that contains the erectile bodies of the penis. This scarring results in curvature and deformity of the erect penis and can have an acute onset within days.^1,2 As a consequence, affected men experience sexual dysfunction and psychological distress. It is estimated that PD is present in 0.3% to 13.1% of all men but is rarely discussed, given significant social stigma.³ The only currently Food and Drug Administration/Health Canada–approved therapy used in PD is collagenase clostridium histolyticum (CCH). CCH is an injected intralesional therapy where collagenase enzymes are used to break down the collagen-based Peyronie’s plaque. It has been shown in several large studies that there is an efficacy rate of approximately 50% in improving curvature.⁴

CCH was recently removed from markets outside the US, leaving the majority of the world’s patients suffering from PD with few treatments.

Fractional CO₂ laser therapy is a topical ablative therapy where abnormal collagen in scarred tissues is destroyed to permit the formation of more organized collagen. The CO₂ laser therapy functions by using a 10,600-nm laser to target water molecules and cause collagen thermolysis within tissue.⁵ This laser is applied in a fractionated pattern to create small columns of thermal injury in the scarred tissue (otherwise known as microthermal zones) between areas of healthy tissue.^5-8 This alternating pattern of healthy tissue and microthermal zones allows for new collagen to form in an organized manner. Although fractionatal CO₂ laser therapy has not been used in urology, it is commonly used in dermatology to treat a variety of conditions. Pertinent conditions that share some degree of pathophysiology include hypertrophic scars and Dupuytren’s disease.⁸

Aims of Study

Aim 1: Evaluate the safety of fractional CO₂ laser therapy in the treatment of PD.

Aim 2: Assess the feasibility of fractional CO₂ laser therapy in improving penile curvature and symptom bother in PD.

Preliminary Data

We have completed a registered clinical trial (NCT04326465) pilot study of fractional CO₂ laser therapy for PD in 5 patients in the chronic phase of Peyronie’s. This paper has been accepted for publication in the Canadian Urological Association Journal.

Penile curvature measurement

Although not powered to assess efficacy, a reduction in primary penile curvature was observed in every patient. At baseline, the median degree of primary penile curvature was 37° (range: 30°-50°). Twenty-four weeks after the initial CO₂ laser therapy, the median degree of primary penile curvature had decreased to 35° (range: 21°-57°), representing a mean difference of −4.8° ± 6.2° and an overall median reduction in penile curvature of 13.2% (range: −7.5% to 30%), a nonstatistically significant reduction from baseline. However, at the 52-week time interval after initial CO₂ laser therapy, the median degree of penile curvature had decreased to 28° (range: 14°-44°), representing a statistically significant reduction in penile curvature compared to baseline (P = .03). The mean change in penile curvature between baseline and at 52 weeks was −11.6° ± 3.6° with an overall median reduction in their penile curvature of 24.3% (range: 16.9%-53.3%).

Peyronie’s Disease Questionnaire

Although a significant difference from baseline was not evident for Peyronie’s Disease Questionnaire (PDQ) scores at 24 weeks, patients did report a significant improvement in their overall PDQ score at the 52-week follow-up (P = .03). No significant differences existed among PDQ-PD when comparing baseline scores (median: 12, range: 11-17) to follow-up scores at either 24 weeks (median: 8, range: 4-12, P = .34) or 52 weeks (median: 7, range: 5-13, P = .25). The PDQ–bother domain showed no significant difference between baseline (median: 7, range: 4-12) and weeks 24 (median: 5, range: 1-11, P = .81) and 52 (median: 4, range: 1-8, P = .62). Patients did not report any significant difference in PDQ–penile pain score; at baseline, patients had a median score of 0 (median: 7, range 0-7), while at 24- and 52-week follow-up, patients reported a median score of 0 (range: 0-5, P > .99) and 2 (range: 0-5, P > .99), respectively.

Adverse events

Adverse events were screened for at every scheduled study visit. In total, throughout the study period, there were 4 Clavien-Dindo grade 1 complications. At week 6 of the study, one patient reported penile pain following laser therapy. There were 2 adverse events reported at week 12 of the study. One patient reported hyperesthesia, which eventually resolved, and another described experiencing temporary penile contusion for 7 days. The last adverse event was reported at the week 24 follow-up, where the patient experienced a penile contusion following his last laser therapy session. There were no reports of abnormal swelling, dysuria, or infection.

Innovation and Impact

Fractional CO₂ laser therapy would represent a potential new therapeutic option for PD patients. Positive results will set the stage for a large clinical trial to test efficacy fully.