Urethral cancer: a comprehensive review endorsed by the Global Society of Rare Genitourinary Tumours

OBJECTIVE: To determine the effectiveness and adverse effects of urethrectomy alone or as part of multimodal therapy (MMT). METHODS: A comprehensive search was conducted across MEDLINE (OVID), EMBASE, LILACS and the Cochrane Central Register of Controlled Trials (CENTRAL) databases, from their inception to the present date. The study cohort comprised individuals aged 16 years and older diagnosed with urethral tumours at any stage who underwent either isolated urethrectomy or urethrectomy as an integral component of MMT. RESULTS: Ninety-two studies comprising 25 480 patients met the inclusion criteria. Surgical outcomes for urethral cancer vary considerably, with 5-year overall survival (OS) ranging from 10% to 68% based on disease extent, approach, and gender. Radiotherapy (RT) alone provides 5-year OS of approximately 40%. Combined regimens provide better outcomes compared to single modalities, including reduced recurrence and enhanced survival. However, trimodal therapy showed survival benefits only for urothelial subtypes, indicating the need to tailor management according to cancer type. MMT with neoadjuvant chemotherapy prior to surgery demonstrated the most consistent survival gains. CONCLUSIONS: The management of urethral cancer demands a nuanced, personalised approach, accounting for factors such as tumour location, sex, and tumour stage. MMT combining surgery, chemotherapy and RT has shown the ability to enhance outcomes in advanced disease. More extensive collaborative studies through specialised centres are imperative to advance evidence-based protocols and refine treatment in order to improve survival.