Many investigators [2–14] have reported adverse events after LDR-brachytherapy. In some studies the adverse events were assessed by the RTOG or RTOG/EORTC scale [2–8], and in others, by the NCI-CTCAE scale [9–13]. Acute and late GU and GI toxicity were mostly evaluated in tetrameric style. To our best knowledge, this is the first study designed to assess the periodical incidence rates of both GU and GI toxicity in patients who had undergone prostate LDR-brachytherapy. Overall, severe adverse events were infrequent in the present study population. Only 6 patients developed grade 3 toxicity (3 patients: acute GU, 3 patients: late GU). No patients developed grade 3 GI toxicity. Stratified by treatment modality, the boost group showed significantly higher incidence rates of late GU and GI toxicity compared with the monotherapy group. On the other hand, there were no significant differences in acute GU and GI toxicity between the two groups.
In particular, acute GU toxicity was well observed in both the monotherapy group and the boost group. Around 80% of patients showed acute GU toxicity. This is comparable to the previous reports [5, 7, 10, 11]. Our previous report has also demonstrated that an objective parameter (uroflowmetry) and a subjective parameter (IPSS) showed transient deterioration in the first 6 months after seed implantation . There were no significant differences between the two groups. However, the grade of toxicity was low, and most patients had grade 1. On the other hand, acute GI toxicity was not frequently observed in either group, as was previously reported [5, 9, 11].
To see the details of the GU and GI toxicities in each follow-up period, there were no significant differences in the incidence rates of hematuria, urinary retention between the monotherapy and the boost groups (Figures 2, 3, 6), but the incidence rates of urinary incontinence, urinary frequency/urgency, proctitis and rectal bleeding were significantly higher in the boost group than in the monotherapy group (Figures 4, 5, 7, 8). In particular, rectal bleeding and proctitis were often observed in the boost group. There were no significant differences in the R100 value between the monotherapy and the boost groups (Table 2). It can however easily be conceived that the total dose to the rectum must be higher in the boost group. Indeed, Snyder et al. reported that the risk of developing grade 2 proctitis was significantly associated with the rectal volume (cut-off value: 1.3 mL) receiving the prescribed dose (160 Gy) . Zelefsky also reported similar results . Ohashi et al. also reported that the predictive parameter of grade 2 or higher GI toxicity was the maximal rectal dose in multivariate analysis . Aoki et al. concluded that R150 was a significant prognostic factor for rectal bleeding in multivariate analysis .
In our present study, IPSS was the only prognostic factor predicting grade 2 or higher acute GU toxicity in multivariate analysis. Zelefsky et al. had similarly concluded that treatment modality (implant alone vs. combined modality) and IPSS were significant predictors of the incidence of acute grade 2 toxicities by CTCAE grading . Keyes et al. also reported that the IPSS was the most significant factor by the RTOG score . On the other hand, there were no significant factors predicting grade 2 or higher acute GI toxicity in our study, because there were only a few patients who developed grade 2 or higher acute GI toxicity. Meanwhile, our present study demonstrated that combination with EBRT was a predictive factor for late GU toxicity. The only predictive factor for late GI toxicity in our present study was R100. This result was comparable to previous reports [6, 8, 9, 11].
There were several limitations in the present study such as a small number of patients (n = 218), a medium follow-up period (42.5 months), a heterogeneous patient population, etc. However, we believe that it is meaningful to assess the periodical incidence rates of both GU and GI toxicity in detail to elucidate the time course changes of urinary and rectal morbidity after seed implantation, because most previous reports had merely evaluated acute and late GU and GI toxicity in acute and late phases.