Combined brachytherapy with external beam radiotherapy for localized prostate cancer: reduced morbidity with an intraoperative brachytherapy planning technique and supplemental intensity-modulated radiation therapy.

PURPOSE: To report the acute and late treatment-related toxicities of combined permanent interstitial (125)I implantation delivered via real-time intraoperative planning and supplemental intensity-modulated radiotherapy (IMRT) for patients with clinically localized prostate cancer. METHODS AND MATERIALS: One hundred twenty-seven patients were treated with a combined modality (CM) regimen consisting of (125)I implantation (110Gy) using a transrectal ultrasound-guided approach followed 2 months later by 50.4Gy of IMRT directed to the prostate and seminal vesicles. Late toxicity was scored according to the NCI Common Terminology Criteria for Adverse Events toxicity scale. The acute and late toxicities were compared to a contemporaneously treated cohort of 216 patients treated with (125)I alone to a prescribed dose of 144Gy. RESULTS: The incidence of Grade 2 acute rectal and urinary side effects was 1% and 10%, respectively, and 2 patients developed Grade 3 acute urinary toxicities. The 4-year incidence of late Grade 2 gastrointestinal toxicity was 9%, and no Grade 3 or 4 complications have been observed. The 4-year incidence of late Grade 2 gastrourinary toxicities was 15% and 1 patient developed a Grade 3 urethral stricture, which was corrected with urethral dilatation. The percentage of patients who experienced resolution of late rectal and urinary symptoms was 92% and 65%, respectively. Multivariate analysis revealed that in addition to higher baseline International Prostate Symptom Score, those patients treated with implant alone compared to CM were more likely to experience Grade 2 acute urinary symptoms. Increased Grade 2 late rectal toxicities were noted for CM patients (9% vs. 1%; p=0.001) as well as a significant increase for late Grade 2 urinary toxicities (15% vs. 9%; p=0.004). CONCLUSIONS: Adherence to dose constraints with combination real-time brachytherapy using real-time intraoperative planning and IMRT is associated with a low incidence of acute and late toxicities. Acute urinary side effects were significantly less common for CM patients compared to those treated with implantation alone. Late Grade 2 rectal and urinary toxicities were more common for patients treated with CM compared to implant alone.