Marieke van Son

135 TOXICITY AFTER ULTRAFOCAL SALVAGE HDR-BRACHYTHERAPY In a previous study, we focused on patient-reported quality of life after ultrafocal salvage HDR-BT(9). Patients reported increased urinary symptoms (especially in the first month after treatment) and a decrease of sexual functioning, while bowel symptoms were neg- ligible. The explorative risk factor analysis in that study revealed that increased base- line urinary symptoms and higher urethra D10% (≥16 Gy) were significantly associated with post-treatment urinary symptoms, and impaired sexual functioning at baseline with post-treatment erectile dysfunction. These results are consistent with the current findings, in which baseline GU/ED toxicity, IPSS ≥14 and urethra D10% ≥17 Gy were sig- nificant predictors for grade ≥2 toxicity. While these analyses highlight the importance of assessing urinary and sexual function before treatment and the need for a strict urethral dose constraint, it also shows the apparent weak relationship between toxicity and other factors such as dose to the bladder, size or stage of the tumor and number of brachytherapy catheters used for the implant. This is important information to find areas of improvement for treatment planning and patient selection, especially since (ultra) focal salvage HDR-BT is being adopted in an increasing number of centers worldwide. Out of the five patients who experienced severe GU toxicity, only two had substantial pre-treatment urinary complaints, consisting of increased frequency (hourly urination), hesitation and mild urge. Pre-treatment IPSS values among these patients ranged be- tween 3 and 18. A common denominator was the relatively high received dose by the urethra, with D10% >17 Gy in 4/5 patients. Although beyond the scope of this study, more research is warranted to explore potential improvements in terms of optimizing tumor control. For instance, dose frac- tionation may offer biological advantages. As described above, different dosimetry and fractionation schemes are being employed for (ultra)focal salvage HDR-BT. Although toxicity seems comparable between these regimens, estimated 3-year biochemical disease-free survival was higher in the multi-fraction studies (±60%) than the sin- gle-dose studies (±44%). Recent results from a comparative trial on the efficacy of whole-gland HDR-BT in the primary setting (1x19 Gy versus 2x13.5 Gy) revealed a clear 5-year cancer control advantage for the two-fraction arm(20). Using patient- and tu- mor-related characteristics, we are currently in the process of developing a prediction model for biochemical failure to further optimize our patient selection criteria. CONCLUSION MRI-guided ultrafocal salvage HDR-BT can be offered as a safe salvage treatment to patients with a local recurrence after primary radiotherapy. Adequate patient selection by baseline symptom assessment and adherence to urethral dose constraints during treatment planning are the most important factors to avoid (severe) toxicity. By offering this treatment, patients may avoid or at least postpone the need for ADT, preventing them from hormone deprivation-related symptoms. Further research in this field should focus on potential areas of improvement in terms of cancer control, aiming to maintain patients ADT-free for as long as possible. 7