Purpose: We examined the factors associated with urinary toxicities because of brachytherapy with iodine-125 with or without supplemental external beam radiotherapy (EBRT) for prostate cancer. Methods and Materials: We investigated 1313 patients with localized prostate cancer treated with iodine-125 brachytherapy with or without supplemental EBRT between 2003 and 2009. The International Prostate Symptom Score (IPSS) and Common Terminology Criteria for Adverse Events data were prospectively determined. Patients, treatment, and implant factors were investigated for their association with urinary toxicity or symptoms. Results: IPSS resolution was not associated with biologically effective dose (BED). Baseline IPSS, total needles, and the minimal dose received by 30% of the urethra had the greatest effect according to multivariate analysis (MVA). Urinary symptom flare was associated with baseline IPSS, age, BED, and EBRT on MVA. Urinary symptom flare and urinary Grade 2 or higher (G2+) toxicity occurred in 51%, 58%, and 67% (p = 0.025) and 16%, 22%, and 20% (p = 0.497) of the <180, 180-220, and >220 Gy BED groups, respectively. Urinary G2+ toxicity was associated with baseline IPSS, neoadjuvant androgen deprivation therapy (NADT), and seed density on MVA. When we divided patients into four groups according to prostate volume (<30 cc or ≥30 cc) and NADT use, urinary G2+ toxicity was most commonly observed in those patients with larger prostates who received NADT, and least in the patients with smaller prostates and no NADT. Conclusions: NADT was associated with urinary G2+ toxicity. Higher dose and supplemental EBRT did not appear to increase moderate to severe urinary toxicities or time to IPSS resolution; however, it influenced urinary symptom flare.
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