Treatment and outcomes of primary urethral cancer treated with radiation therapy

Primary urethral cancer (PUC) is a heterogeneous and aggressive malignancy that accounts for less than 1% of all genitourinary malignancies. Due to its rarity, no prospective data exists to guide treatment paradigms. The purpose of this study is to report our clinical experience treating PUC with external beam radiation therapy (EBRT) with or without high-dose rate brachytherapy (HDR-BT) as part of curative-intent therapy.

Adult patients who had received treatment for PUC between January 2000 and December 2023 within a multi-center academic hospital system were queried in the medical record. Patients who received EBRT with or without HDR-BT as part of curative-intent treatment, including in the neoadjuvant, adjuvant, and definitive treatment settings, were included. Baseline clinicopathologic features, treatment details, and follow-up were recorded. The primary endpoint locoregional control (LRC), defined as the absence of recurrence at the primary site or regional lymph nodes, was estimated using the Kaplan Meier method and compared with the log-rank test. Cox regression analysis was performed to assess factors associated with LRC. A p-value of <0.05 was considered statistically significant.

Seventy patients who received treatment for PUC were identified. Among these, 21 received EBRT as part of curative-intent treatment (including 8 in the adjuvant setting, 11 in the definitive setting, and 2 in the neoadjuvant setting). Among these 21 patients, 10 also received HDR-BT. The 2-year locoregional control rate was 100% versus 85.7% in patients who did and did not receive HDR-BT, respectively (p = 0.49). Univariate analysis did not show a significant correlation of sex, stage, race, receipt of systemic therapy, EBRT dose, or HDR-BT use with locoregional control. Among the 10 patients that received HDR-BT, one patient experienced a chronic grade 3 fistula, however, fistula was present after biopsy and before radiation. Two of the 10 patients experienced a grade 3 stricture which resolved over time with dilation. No patients experienced grade 4 or 5 toxicity.

PUC is a rare malignancy with little data to guide treatment paradigms. HDR-BT may offer improved locoregional control with acceptable toxicity in this small study. Larger studies are needed to refine optimal therapeutic approach and radiation treatment technique.