GSOR19 Presentation Time: 12:00 PM: High-Dose Rate Brachytherapy for Female Urethral Cancer: A Multi-Center Review Over Two Decades

Abstract

<h3>Purpose</h3> Primary urethral cancer is an uncommon and aggressive malignancy that accounts for less than 1% of all genitourinary malignancies. Treatment paradigm often includes high-dose rate (HDR) brachytherapy, however data on treatment techniques, clinical outcomes, and toxicity remain limited. This study reviews our institutional experience treating female urethral cancer with brachytherapy over the past 2 decades. <h3>Materials and Methods</h3> The medical records of all adult female patients who had received treatment for urethral cancer between January 2000 and December 2021 within a multi-center academic hospital system were queried. Baseline clinicopathologic features, radiation treatment details, and outcomes were recorded. HDR brachytherapy dose homogeneity index (DHI) was defined as (V100 - V150)/V100. Survival analysis was performed using multivariable Cox proportional hazards regression. <h3>Results</h3> There were 37 females with urethral cancer identified in this study, of whom 10 (median age at diagnosis 65 years, median follow-up 35 months, see Table 1) underwent HDR brachytherapy. All 10 patients received a combination of external beam radiotherapy (EBRT) and HDR brachytherapy. Eight patients received treatment for primary disease, and 2 patients for recurrent disease. HDR brachytherapy was delivered in the neoadjuvant (10%), adjuvant (30%), and definitive treatment settings (60%). One patient received adjuvant intraoperative radiotherapy (IORT) 15 Gy in 1 fraction after pelvic exenteration for a positive margin, followed by adjuvant EBRT. Non-IORT brachytherapy regimens in the remaining 9 patients ranged from 18.5 Gy to 33.0 Gy in 3-5 fractions. Median size of HR-CTV was 22 cc (range 11-76 cc). Perineal Syed template with a urethral catheter was used in 7 patients; 6 of these patients were also treated with interstitial catheters (median 5 catheters, range 4-8). During conventionally fractionated EBRT, T4 disease (40%) was treated to 54.0-64.8 Gy and gross nodal disease (20%) to 55.8-59.4 Gy. Total EQD2 to the HR-CTV D90 exceeded 85 Gy in all cases except one, where an emerging fistula invoked under-coverage (71 Gy). The constraints of bladder D_2cc < 90 Gy and rectum D_2cc < 75 Gy were each unmet by one patient (20%); both of these patients had T4 disease. Acute toxicities from radiation included grade 2 urinary frequency (40%) and diarrhea (30%), while chronic toxicities included grade 2 pelvic pain (40%), grade 3 urethral stricture requiring dilation (20%), and grade 2 vesicovaginal (10%) and urethrocutaneous (10%) fistula. Brachytherapy DHI less than 0.2 was 75% sensitive and 100% specific for predicting the development of a fistula or urethral stricture. Among all 37 women in this cohort, the 10 who received brachytherapy had a trend toward longer recurrence-free survival (median 43 vs. 22 months, HR 0.35, 95% CI 0.11-1.13, <i>P</i>=0.079) after adjustment for stage and age at diagnosis. <h3>Conclusions</h3> Primary urethral cancer is an uncommon malignancy with sparse evidence to guide treatment. Brachytherapy may offer improved freedom from recurrence, but there is risk of severe toxicity especially when treatment volumes are large or dose homogeneity is poor. Additional studies are needed to further refine target dose and normal tissue constraints.