Urethral Adenocarcinoma: A Rare Malignancy With Poor Oncologic Outcomes Despite Neoadjuvant Treatment and Consolidative Therapy

Purpose: Primary urethral adenocarcinoma (PAC) is a rare malignancy associated with poor outcomes. There are 2 primary subtypes—clear cell adenocarcinoma (CCAC) and non–clear cell adenocarcinoma (nCCAC). In this study, we compare oncologic outcomes between CCAC vs nCCAC histological subtypes and describe differences in treatment modalities. Materials and Methods: We performed a retrospective review of patients diagnosed with PAC at our institution between 1993 to 2024. Survival analysis was stratified by histologic subtype (CCAC vs nCCAC) and primary treatment modality. Survival outcomes were stratified by patient age, neoadjuvant therapy (NAT), primary treatment modality, clinical stage, and histological subtype. Results: Of the 35 patients identified, the majority were female, were Black, and presented with locally advanced disease. Most of the patients were treated with radiotherapy (XRT) or surgical extirpation. There were no significant differences in clinical staging or histologic subtype between the 2 treatment modalities. Ten patients were treated with XRT, and 21 patients underwent primary surgical extirpation. Most of the patients received NAT. Locally advanced disease on final pathology was common for both histological subtypes. No patients were downstaged after surgical extirpation, despite nearly all receiving NAT. Survival was significantly better for CCAC vs nCCAC. There was no statistical difference in survival when comparing by treatment modality. Conclusions: PAC represents a rare, aggressive form of cancer. Favorable outcomes among the CCAC cohort may reflect a more favorable disease biology. Despite most of the patients receiving NAT, there were no patients with pathologic downstaging suggesting current neoadjuvant regimens are suboptimal and novel systemic strategies are needed for tumor downstaging to facilitate optimal local tumor control and improved oncologic outcomes.