The Journal of Urology | 2019
MP38-07\u2003URETHRAL MELANOMA – CLINICAL, PATHOLOGICAL AND MOLECULAR CHARACTERISTICS
Abstract
INTRODUCTION AND OBJECTIVES: Mucosal melanoma of the urethra is a rare disease with distinct clinical and pathological characteristics and poor outcomes compared to cutaneous melanoma. We describe the clinical, pathological and molecular characteristics of urethral melanoma. METHODS: After receiving IRB approval, we identified 31 patients treated at our center for urethral melanoma between 1986-2017. Clinical and pathological characteristic were obtained from patients’ medical records. The results of targeted exome sequencing using MSK IMPACT (n=7) or targeted gene sequencing of BRAF, KIT and/or NRAS (n=7) were summarized and compared to the results of MSK IMPACT testing of cutaneous melanomas (n=190). Survival outcomes were estimated with the Kaplan-Meier method. RESULTS: The study cohort included 29 females and 2 males with a median age of 72 years (IQR 59-79). Charlson Comorbidity Index was >3 in 23 patients (74%). A urethral/ vulvar mass was apparent in 65% of patients and 42% presented with hematuria or vaginal bleeding. External genitalia were involved in 21 patients. Stage at diagnosis was localized in 21 patients (68%), regional/ nodal in 7 (23%) and distant/ metastatic in 3 (10%). Mutations in CDKN2B and PAK1 were more prevalent in urethral melanoma while TERT and BRAF mutations were more frequent in cutaneous melanoma (Figure 1). Initial treatment included surgery in 25 patients; 8 had multimodal treatment. Median follow-up for survivors was 30 months (IQR 25-81); 25 of the 28 patients with loco-regional disease recurred and/or progressed at a median of 10 months (IQR 8-31). Patients who did not recur either died of other causes or were lost to follow-up at a median of 8 months (IQR 7-19). Treatment for recurrent disease included surgery (14/25 patients, 56%), radiotherapy (7/25, 28%), chemotherapy (10/25, 40%), targeted therapy (2/25, 8%) and immunotherapy (14/25, 56%). 22 patients died during follow-up, 16 from metastatic melanoma. The 2- and 5-year cancer-specific survival rates were 79% and 48%, respectively. No significant change in survival was observed based on year of diagnosis (HR=1.035 per year; 95% CI (0.96-1.12); p=0.39). CONCLUSIONS: Survival remains poor for patients with urethral melanoma and is unchanged over the time studied. Our findings support a unique mutational landscape of urethral melanoma compared to that of cutaneous melanoma. Figure. No caption available. Source of Funding: This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.