Prostate cancer is one of the most frequently diagnosed cancers in developed countries. Permanent iodine-125 implant brachytherapy (PI) with or without external beam radiotherapy (EBRT) has been one of the standard definitive radiotherapies for localized prostate cancer. Prostate cancer is curable when treated early by surgery or radiotherapy, hence many of these patients live survive longer. It is well known that the 5-year survival rate for most men with local or regional prostate cancer is nearly 100%. Genitourinary toxicity as an adverse event caused by prostate radiotherapy affects patients’ quality of life. However, there is few study which evaluate lower urinary tract symptoms of prostate cancer patients that were treated with PI over more than 5 years. It is useful to know the long-term changes of lower urinary tract symptoms of prostate cancer survivor. We therefore investigated changes of lower urinary tract symptoms of prostate cancer patient who were treated with PI using International Prostate Symptoms Score (IPSS), Overactive Bladder Symptoms Score (OABSS) and uroflowmetry

This study was approved by the institutional review board. From August 2004 to December 2013, 313 patients underwent PI for localized prostate cancer at our hospital. All PI were performed with iodine-125 seeds using the ultrasonography-guided intraoperative transperineal technique. The prescribed minimum peripheral doses of iodine-125 seeds were 145Gy for PI alone and 104Gy for PI + EBRT. Neoadjuvant androgen deprivation therapy (ADT) was used for reducing prostate volume and/or for anticancer effects as required. Alpha-1 blocker was routinely initiated on all patients after PI to reduce risk of urinary retention, and discontinued after recovery of lower urinary tract symptoms. To evaluate lower urinary tract symptoms, IPSS and OABSS were assessed at pretreatment; at 1, 3, 6, 9, 12, 24, 36, 48 and 60 months after PI and annually thereafter. Uroflowmetry was also assessed at pretreatment; 1, 3, 6, 12, 36 and 60 months and annually thereafter. Multivariable linear regression model with robust sandwich estimator was used to evaluate the association between outcome and month adjusting for covariate. The covariates were determined at enrollment included age, body-mass index (BMI), number of needle at PI, biologically effective dose (BED), the minimal dose (Gy) received 5% of the urethra (UD5), with or without EBRT, risk classification and each pretreatment value for outcome. Nonlinear associations between month and outcome were assessed by including non-linear cubic splines in the regression model. In addition, we incorporated an interaction term to assess the effect modification of pretreatment values. A p value <0.05 was considered statistically significant.

The median age and BMI at baseline, median prostate-specific-antigen at diagnosis of prostate cancer, and median prostate volume at PI were 66 years (range; 50-78 years), 23.7 kg/m2 (range; 16.0-39.9 kg/m2), 6.3 ng/ml (range; 1.9-38.3 ng/ml), and 21.6ml (range; 8.6-57.6 ml), respectively. The median followup duration was 84 months (range; 1-168). The median Gleason score was 7 (range; 5-9). Based on modified D’Amico risk classification, 135 patients (43.1%), 157 patients (50.2%) and 21 patients (6.7%) were low risk, intermediate risk and high risk, respectively. Neoadjuvant ADT was administered to 259 patients (82.7%). The PI-alone consisted of 189 patients (60.4%) and the PI + EBRT consisted of 124 patients (39.6%). The dosimetry data of BED, UD5 were 191.8Gy (range; 121.0-261.5Gy) and 220.4Gy (range; 110.5-395.3Gy), respectively. The mean IPSS, OABSS, maximal voiding rate (Qmax), voided volume, and post-voided residual before PI were 6.6 (range 0-29), 3.1 (range; 0-10), 18.9 ml/s (range; 6.5-49.5ml/s), 293.1ml (range; 11.6-844ml), and 14.8ml (range; 0-74ml), respectively. IPSS increased at 3 months after PI with the mean score 17.3, and the score decreased at 36 months with the mean score 7.7. Non-linear regression analysis revealed that duration was significantly related change of IPSS (p<0.001) and 36 months after treatment with PI the score remained consistent level. In addition, pretreatment IPSS significantly modified the association between change of IPSS and month (p=0.023). OABSS also increased at 3 months after PI with the mean score 7.0, and the score decreased at 9 months after PI with the mean score 4.0. Non-linear regression analysis revealed that duration was significantly related change of OABSS (p<0.001). Interestingly, non-linear regression analysis revealed that OABSS increased again after 60 months unlike IPSS. In addition, pretreatment OABSS significantly modified the association between change of OABSS and month (p=0.017). Non-linear regression analysis of uroflowmetry revealed transient deterioration of Qmax, voided volume, and post-voided residual, and these factors recovered until 36 months after PI. It is noteworthy that Qmax and post-voided residual remain after improvement, voided volume became decreased again. Qmax, voided volume and post-voided residual did not modify the relationship between outcome and month significantly, but we could confirm weak tendency for effect modification (p-value for interaction was p=0.06, p=0.151 and p=0.057.).

IPSS, OABSS, uroflowmetry showed similar results in change until five years of treatment. However, OABSS and voided volume showed different results in change compared with IPSS, Qmax, and post-voided residual after five years of treatment. IPSS is a part of scale for dysuria. Qmax and post-voided residual also correlates with dysuria. Therefore, these factors showed similar behavior in the changes. On the other hand, OABSS was the scale of urine collection disorder. Decreased voided volume could explain exacerbation of OABSS. It is also noted that advancing in years caused the likelihood of these changes.

To the best of our knowledge, this is the longest prospective study of voiding symptom in prostate cancer patient treated with PI using IPSS, OABSS, and uroflowmetry. First five years, changes of symptoms of dysuria and urine collection disorder were similar, but urine collection disorder became worse again after five years of treatment. It is useful to know the urine collection disorder may occur in prostate cancer patients more than five years after PI.