Clinical and histological predictors of treatment outcomes in primary urethral carcinoma.

Introduction and objectives: Primary urethral cancer (PUC) is a rare malignancy (<1% of all urological cancers). High-grade or advanced cases often require multimodal treatment, including surgery, chemotherapy, immunotherapy, and radiotherapy. This study reviews outcomes and predictors of recurrence and survival in PUC at our tertiary care center.

Methods: We conducted a retrospective chart review at a single tertiary care institution, identifying 251 urethral cancer cases from January 1, 2014, to July 1, 2024. After excluding 163 cases due to non-PUC or insufficient follow-up, 88 cases remained. We collected data on demographics, tumor pathology, treatment modality, and oncologic outcomes. Primary outcomes included overall survival (OS) and recurrence-free survival (RFS). Cox regression was used to assess predictors of OS and RFS.

Results: The cohort included 53 men (60%), with a median age of 64 years. Squamous cell carcinoma was most common (51%), followed by urothelial carcinoma (20%), adenocarcinoma (20%), and variant histology (8%). At presentation, 45% had locally advanced disease (T3/T4), 23% had nodal involvement, and 12% were metastatic. Treatment included surgery (82%), systemic therapy (40%), radiation (36%), and multimodal therapy (41%). Multivariable analysis showed that nonurothelial histology (HR = 8.09, P = 0.04) was associated with increased risk of recurrence, while nodal involvement (HR = 5.63, P < 0.01) predicted worse OS.

Conclusion: In this large North American cohort, nodal involvement predicted worse survival, while nonurothelial histology was linked to shorter recurrence-free survival. These findings support multidisciplinary care and highlight the need for prospective registries in this rare malignancy.