LAUSR

BACKGROUND Vulvar Paget disease is an extremely rare skin disorder, which is most common in postmenopausal women. The majority of vulvar Paget disease cases are non-invasive, however, it may be invasive or associated with an underlying vulvar or distant adenocarcinoma. The current treatment of choice for non-invasive vulvar Paget disease is wide local excision, which is challenging due to extensive intraepithelial spread and may cause severe morbidity. Recurrence rates are high, ranging from 15% to 70%, which emphasizes the need for new treatment options. Imiquimod, a topical immune response modifier, has been shown to be effective in a few studies and case reports and is a promising new treatment modality. OBJECTIVE To prospectively investigate the efficacy, safety, and quality of life in patients with non-invasive vulvar Paget disease using a standardized treatment schedule with 5% imiquimod cream. STUDY DESIGN The Paget Trial is a multicenter prospective observational clinical study including seven tertiary referral hospitals in the Netherlands. Twenty-four patients with non-invasive vulvar Paget disease were treated with topical 5% imiquimod cream three times a week for 16 weeks. The primary efficacy outcome was the reduction in lesion size at 12 weeks after the end of treatment. Secondary outcomes were safety, the clinical response after 1 year and quality of life. Safety was assessed by evaluation of adverse events and tolerability of treatment. Quality of life was investigated with three questionnaires taken before, during, and after treatment. RESULTS Data was available for 23 patients, 82.6% of these patients responded to therapy. A complete response was reported in 12 patients (52.2%) and seven patients (30.4%) had a partial response. A histological complete response was obtained in ten of the twelve patients with a complete response. Patients experienced side effects like fatigue (66.7-70.9%), headaches (16.7-45.8%), and almost 80% needed painkillers during treatment. Eight patients (34.8%) adjusted the treatment protocol into two applications a week, and three patients (13.0%) stopped treatment because of the side effects after four to eleven weeks. Treatment improved the quality of life, whereas during treatment a slight, temporarily negative impact was seen. Two patients with a complete response developed a recurrence within one year after treatment. Follow-up showed six patients with a non-invasive recurrence, after a median of 31 months (14 to 46 months) after the end of treatment. CONCLUSION Topical 5% imiquimod cream can be an effective and safe treatment alternative for non-invasive vulvar Paget disease. Topical 5% imiquimod cream can be considered as an alternative to surgical excision.