A Systematic Review of the Clinical Features, Management, and Outcomes in Urethral Squamous Cell Carcinoma

Primary urethral squamous cell carcinoma (SCC) is a rare and aggressive malignancy, accounting for a minority of genitourinary cancers but presenting significant diagnostic and therapeutic challenges. Due to its rarity, limited data exists to guide standardized management. We aim to systematically review the available literature on urethral SCC, with a focus on epidemiology, clinical presentation, histological characteristics, treatment modalities, and patient outcomes. A comprehensive systematic search of PubMed was conducted for studies published between January 1995 and December 2025, with data extraction performed in accordance with PRISMA guidelines. The inclusion criteria encompassed studies involving patients with histologically confirmed urethral SCC. Retrospective studies and case series/reports were included due to the absence of prospective trials. Primary outcomes included overall survival and disease-specific survival, while secondary outcomes encompassed recurrence rates, treatment-related complications, and quality of life. A total of 27 studies (15 retrospective and 12 case reports/series) were included, representing 2,917 male and 1,292 female patients. The majority of patients were over 60 years of age. The most common presenting symptoms included lower urinary tract obstruction, hematuria, and pelvic mass. High-grade tumors (Grade 3 and 4) were most frequently observed. Treatment modalities varied widely and included transurethral resection, urethrectomy, chemotherapy, and radiotherapy, often in combination. Recurrence was observed in 139 patients, while metastasis was reported in 51. The reported 5- to 10-year survival rates ranged from 30% to 60%. Urethral SCC is a highly aggressive and understudied malignancy with heterogeneous clinical features and treatment practices. The findings underscore the urgent need for standardized staging criteria, prospective multicenter studies, and consensus-driven treatment guidelines. Improved recognition and tailored therapeutic strategies are critical to enhancing outcomes in this rare but impactful cancer.