Secondary bladder cancer during long-term follow-up after iodine-125 permanent seed implantation for localized prostate cancer



      Brachytherapy for prostate cancer treatment may induce secondary bladder cancer during long-term follow-ups. This study reviews the risk and tumor characteristics of secondary bladder cancer after brachytherapy.


      This single-institution retrospective study included 1162 patients treated with low-dose-rate permanent seed implantation brachytherapy with iodine-125, with or without external beam radiation therapy, for localized prostate cancer. We calculated and compared the rates of secondary bladder cancer among patients treated with brachytherapy and radical prostatectomy (n = 218) before and after a propensity score-matching analysis. Possible risk factors for secondary bladder cancer, such as patient age and external beam radiation therapy administration, were analyzed.


      Of 1162 patients with a median follow-up period of 11.4 (range: 0.7–15.5) years, 26 presented with urothelial carcinomas and 1 with adenocarcinoma at a median of 8.9 (range: 2.9–14.0) years after brachytherapy, although the incidence rates of secondary bladder cancer after brachytherapy were not significantly different from those after radical prostatectomy. No significant risk factors for secondary bladder cancer were identified. The initial symptoms of secondary bladder cancer were gross hematuria (74%) and microscopic hematuria with positive urine cytology (15%). Among 26 cases of secondary urothelial carcinoma, 54% were high-grade and 46% were invasive. After brachytherapy, invasive urothelial carcinoma occurred later than noninvasive urothelial carcinoma (p = 0.01).


      Considering the aggressive malignancy of secondary bladder cancer, cystoscopy and urine cytology should be performed for further investigation of the causes of gross or microscopic hematuria and rule out secondary bladder cancer in cases followed longer than 3 years after brachytherapy.



      BCA (Bladder cancer), BED (Biological effective dose), CT (Computed tomography), D90 (Minimal dose delivered to 90% of the prostate volume), EBRT (External beam radiation therapy), LDR (Low-dose-rate permanent seed implantation brachytherapy with iodine-125), LUTS (lower urinary tract symptoms), NCCN (National Comprehensive Cancer Network), PCA (Prostate cancer), PSA (Prostate-specific antigen), RP (Radical prostatectomy), TUR (Transurethral resection of bladder tumor), UC (Urothelial carcinoma)
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