Risk Factors for Ureteral Stricture After Radiochemotherapy Including Image Guided Adaptive Brachytherapy in Cervical Cancer: Results From the EMBRACE Studies

Abstract

Ureteral stricture is a rare but severe side effect of radiation therapy for locally advanced cervical cancer. This report describes the incidence and risk factors for ureteral stricture in a large patient cohort treated with 3-dimensional imageguided adaptive brachytherapy and radiochemotherapy within the EMBRACEstudies. A total of 1860 patients were included. Treatment consisted of external beam radiation therapy (45-50Gy in 25-30 fractions), concomitant cisplatin, and image guided adaptive brachytherapy. Grade 3 to 4 ureteral strictures were assessed with Common Terminology Criteria for Adverse Events v. 3.0. Risk factors for grade 3 to 4 ureteral stricture were analyzed. These factors included age, hydronephrosis on imaging at time of diagnosis, TNM stage, high-risk clinical target volume, laparoscopic staging, chemotherapy, radiation therapy doses to targets and organs at risk, applicator type, intracavitary versus intracavitary/interstitial technique, and dose rate. At a median follow-up of 34months (range, 2-163), 31 patients received diagnoses of grade 3 to 4 ureteral stricture. Actuarial 3- and 5-year risk for ureteral stricture grade 3 to 4 was 1.7% and 2.1%, respectively, for all patients. Advanced tumor stage T3-4 with hydronephrosis at diagnosis was the only independent risk factors for ureteral stricture (P=.01). Patients with TNM stage T1 (n=359) had a low risk of 0.4% and 1.0% at 3 and 5years, and those with T2 (n=1085) had a low risk of 1.0% and 1.0% at 3 and 5years, respectively. Patients (n=274) with T3-T4 without hydronephrosis at diagnosis had a 3- and 5-year risk of 2.2% and 4.8%, respectively, compared with 11.5% and 11.5%, respectively, in those with baseline hydronephrosis (n=142). Severe to life-threatening ureteral stricture occurs rarely in patients with locally advanced cervical cancer with T1-2 tumors. The risk for ureteral stricture is significantly increased in patients with T3-T4 tumors with hydronephrosis at diagnosis.