Acute genitourinary toxicity after high dose rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: Second analysis to determine the correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity

Abstract

We have been treating localized prostate cancer with high-dose-rate (HDR) brachytherapy combined with hypofractionated external beam radiation therapy (EBRT) at our institution. We recently reported the existence of a correlation between the severity of acute genitourinary (GU) toxicity and the urethral radiation dose in HDR brachytherapy by using different fractionation schema. The purpose of this study was to evaluate the role of the urethral dose in the development of acute GU toxicity more closely than in previous studies. For this purpose, we conducted an analysis of patients who had undergone HDR brachytherapy with a fixed fractionation schema combined with hypofractionated EBRT. Among the patients with localized prostate cancer who were treated by 192-iridium HDR brachytherapy combined with hypofractionated EBRT at Gunma University Hospital between August 2000 and November 2004, we analyzed 67 patients who were treated by HDR brachytherapy with the fractionation schema of 9 Gy x two times combined with hypofractionated EBRT. Hypofractionated EBRT was administered at a fraction dose of 3 Gy three times weekly, and a total dose of 51 Gy was delivered to the prostate gland and seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography-guided HDR brachytherapy. The planning target volume was defined as the prostate gland with a 5-mm margin all around, and the planning was conducted based on computed tomography images. The tumor stage was T1c in 13 patients, T2 in 31 patients, and T3 in 23 patients. The Gleason score was 2-6 in 12 patients, 7 in 34 patients, and 8-10 in 21 patients. Androgen ablation was performed in all the patients. The median follow-up duration was 11 months (range 3-24 months). The toxicities were graded based on the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer toxicity criteria. The main symptoms of acute GU toxicity were dysuria and increase in the urinary frequency or nocturia. The grade distribution of acute GU toxicity in the patients was as follows: Grade 0-1, 42 patients (63%); Grade 2-3, 25 patients (37%). The urethral dose in HDR brachytherapy was determined using the following dose-volume histogram (DVH) parameters: V30 (percentage of the urethral volume receiving 30% of the prescribed radiation dose), V80, V90, V100, V110, V120, V130, and V150. In addition, the D5 (dose covering 5% of the urethral volume), D10, D20, and D50 of the urethra were also estimated. The V30-V150 values in the patients with Grade 2-3 acute GU toxicity were significantly higher than those in patients with Grade 0-1 toxicity. The D10 and D20, but not D5 and D50, values were also significantly higher in the patients with Grade 2-3 acute GU toxicity than in those with Grade 0-1 toxicity. Regarding the influence of the number of needles implanted, there was no correlation between the number of needles implanted and the severity of acute GU toxicity or the V30-V150 values and D5-D50 values. It was concluded that HDR brachytherapy combined with hypofractionated EBRT is feasible for localized prostate cancer, when considered from the viewpoint of acute toxicity. However, because the urethral dose was closely associated with the grade of severity of the acute GU toxicity, the urethral dose in HDR brachytherapy must be kept low to reduce the severity of acute GU toxicity.