As shown in the many previous studies, low-dose-rate brachytherapy (LDRB) is one of the effective treatment options, and is currently a standard treatment for localized prostate cancer. Although LDRB is generally reported to be well tolerated, lower urinary tract symptoms (LUTS) often occur following implantation of LDRB. The presumed causes of LUTS after LDRB are the traumatic effect of needle insertion, direct irritation of peripheral nerves by irradiation, edematous change following seed implantation, and inflammatory changes in urethra and prostate following radiation exposure (1, 2). Even though the cause of LUTS after LDRB is multi-factorial, investigation about the pathogenesis is important to establish adequate treatment for LUTS after LDRB. However, the mechanisms and process of LUTS after LDRB have not been proved yet. 
Moreover, the previous report indicated the severity of LUTS after LDRB synchronized to decrease of prostate volume (PV) (3). These results indicate that atrophic change of prostate tissue might mainly cause LUTS after LDRB. However, the changes of PV have different degree and many variations including enlargement in size due to intraprostatic bleeding or edema after implantation. Therefore, relationship between PV and LUTS should be investigated in detail to clarify the pathogenesis of LUTS after LDRB. Herein, we evaluated the impact of PV change on severity of LUTS after LDRB focusing on the two cohorts; increase and decrease of prostate volume.  The aim of this study is to clarify the pathogenesis of LUTS after LDRB for establishment of adequate management for LUTS after LDRB.

Prostate cancer patients who received LDRB from 2014 to 2018 were retrospectively enrolled in this study. Very low risk, low risk, and intermediate risk localized cancer were eligible for LDRB in accordance with National Comprehensive Cancer Network risk classification. Patients with T2c, prostate specific antigen (PSA) > 10.0 ng/mL, and Gleason score 4+3 were received external beam radiation therapy (EBRT) before LDRB. Patients who have large prostate (40 cm3<), severe LUTS due to neurogenic bladder, and more than 50 mL of residual urine volume (RUV) were excluded for LDRB. International Prostate Symptom Score (IPSS), IPSS-QOL, Overactive Bladder Symptom Score (OABSS), uroflowmetry including voided volume (VV), maximum flow rate (Qmax), RUV, and PV were evaluated at the preimplantation stage and 1, 3, 6, 9 and 12 months after implantation of LDRB. RUV and PV was measured by transabdominal ultrasound by a single ultrasonographer. 
First, clinical parameters were compared with the baseline data. Correlation of PV and IPSS was also evaluated in all of the patients. Second, for the sub-analysis to assess the role of PV change after LDRB, the patients were separated into two groups; PV increase group or PV decrease group. PV 3 months after LDRB were used to separate the patients.
Paired t-test was used for comparison of all of the basic and clinical data at 1, 3, 6, 9, and 12 months after LDRB. Spearman’s correlation was used to evaluate the correlation between PV and IPSS. Clinical background and parameters were compared among the groups including age, initial PSA, Gleason score, T stage, IPSS, IPSS-QOL, OABSS, VV, Qmax, RUV, and PV. For the statistical analysis, unpaired t-test and chi square test ware used to comparison among the groups.

Eighty-four patients of prostate cancer were enrolled in this study. The basic clinical characteristics of the patients are shown in Table 1. Comparisons between PV increase group and PV decrease group were also included in Table 1.
Change of PV and IPSS were presented in Figure 1. PV decreased and IPSS increased at 3 months after LDRB, and both recovered in a process of a year. IPSS-QOL, OABSS, Qmax, VV, and RUV were changed similarly to IPSS after the implantation of LDRB. Figure 2 demonstrate the correlation between change of PV and IPSS 3 months after LDRB (at the peak of decrease of PV and increase of IPSS). However, there was no significant correlation, and coefficient of correlation was 0.103. The comparisons of PV increase group and PV decrease group were presented in Figure 3a-c. IPSS and Qmax were similarly changed in the 2 groups. There are no statistical changes among the groups in all of the process. Other parameters also changed similarly in the 2 groups.

LUTS reached the peak 3 months after LDRB synchronizing to decrease of PV. From 3 months to 1 year after LDRB, LUTS improved as PV recovery. However, PV and LUTS after LDRB showed no significant correlation, and there is much individual difference of PV change after LDRB. Moreover, there are no statistical differences of IPSS between PV increase group and PV decrease group. These results indicate that change of PV after LDRB does not associate with LUTS after LDRB. If so, LUTS after LDRB is not due to the pathogenesis related to PV change, such as edema, hematoma, inflammation, and atrophic change of prostate induced by radiation. Therefore, the pathogenesis of LUTS after LDRB might be independent factors from those leading PV change, such as direct neural irradiation. In fact, high radiation activities theoretically remain almost 3 months after LDRB implantation.

PV change synchronized severity of LUTS after LDRB. However, PV change might not associate with LUTS after LDRB. Other pathogenesis such as direct neural irritation by irradiation was indicated as the main cause of LUTS after LDRB.

Mallick S, Azzouzi R, et al. Urinary morbidity after 125I brachytherapy of the prostate. BJU Int. 2003; 92(6): 555-8.
Keyes M, Miller S, et al. Predictive factors for acute and urinary toxicity after permanent prostate brachytherapy: long-term outcome in 712 consecutive patients. Int J Radiat Oncol Biol Phys. 2009; 73: 1023-32.
Daimon H, Minagawa T, et al.  Assessment for correlation between prostatic volume change and lower urinary tract symptoms after low-dose-rate brachytherapy for prostate cancer. ICS Annual Meeting 2017.