Advances in the management of genitourinary melanomas

Michael J. Carr, James Sun, Philippe E. Spiess, Jonathan S. Zager


Primary mucosal melanomas of the genitourinary (GU) tract are rare but aggressive tumors that can affect mucosal surfaces of the GU tract and urinary tract. They exhibit distinct biological differences compared to cutaneous melanomas and other mucosal melanomas. There is also significant variation among genitourinary melanoma subtypes. Little is known about the etiology of this disease or the natural history and there is currently no established staging system. Treatment is challenging as diagnosis is typically made at a later stage of disease and response to immunotherapy is not robust. Targetable activating mutations are infrequent, the most common being in c-KIT, expressed in one-third or less of patients. Surgical resection remains the standard of care, and emphasis on less invasive resection is recommended whenever possible. Initial adjuvant treatment typically consisted of dacarbazine-based chemotherapy, though recent advances in effective systemic immunotherapies have shown promising results. Existing data are insufficient to make evidence-based recommendations regarding the best course of treatment and much remains unknown regarding the best management of this disease. Given the rarity of GU melanomas, specific clinical trials are difficult to design. Ongoing trials of mucosal melanomas are underway which may identify new effect treatment modalities.