Treatment options and outcomes of men with Penile Intraepithelial Neoplasia (PeIN): A systematic review

Abstract

Introduction & Objectives: Penile intraepithelial neoplasia (PeIN) is a rare skin condition characterised by dysplastic changes of the epidermal squamous cells which does not extend beyond the basement membrane. Successful treatment options for PeIN with minimal side effects are essential as progression into invasive cancer may require more extensive surgery in a cosmetically sensitive anatomical location. Our aim was to systematically review the published literature for treatment options and outcomes of men with PeIN. Materials & Methods: We performed a systematic review to summarise treatment options and outcomes in the published literature using the electronic databases MEDLINE, EMBASE and Cochrane Database of Systematic Reviews. Results: Of 1594 publications 94 full-text manuscripts of publications were screened and finally 19 studies contributing 691 patients with PeIN were included. Topical therapies included imiquimod and Fluorouracil (5-FU) with complete response rates in 40-100% and 48-74% respectively. Progression after Imiquimod and 5-FU was observed in 20% and 11% respectively. Adverse events were observed in 10% during imiquimod and in 5-12% during 5-FU with the most common being local inflammation causing pain and severe irritation. Phimosis was observed in 5% treated with imiquimod. Discontinuation of treatment in men treated with imiquimod and 5-FU was described in 10% and 11% and one study reported that 11% of men treated with 5-FU were admitted to hospital because of severe inflammation and pain. There were several energy-based therapies discussed in the literature including Yag laser, CO2 laser and phototherapy. Laser treatment demonstrated higher rates of total response (52%-100%). Recurrence was reported in 7%-48%. A significant side effect following laser treatment was a change in penile sensitivity including increased sensitivity in 50% and decrease sensitivity in 15%. Phototherapy led to complete response in 40%-70% but recurrence was observed in 30% and progression in 36%. Surgical treatment of PeIN was associated with recurrence in 4%-30%. Circumcision cleared all preputial PeIN whereas recurrence after surgical treatment of PeIN of the glans was observed in 25% after wide local excision, 4% after Mohs surgery, 5% after total glans resurfacing and 10% after Glansectomy. Conclusions: In summary the data on treatment options and outcomes of men with PeIN is limited and based on small retrospective cohort studies. Our conclusion from the published literature is that circumcision represents the most effective treatment for preputial PeIN whereas several treatment options should be discussed in men with PeIN of the glans and ideally assessed in prospective studies.