General discussion and future perspectives 221 Part II. MRI-guided radiotherapy for locally recurrent prostate cancer Focal salvage MRI-guided high-dose-rate brachytherapy MRI-guided radiotherapy is not only applicable to the primary treatment setting. MRI-guidance has been employed for the treatment of recurrent prostate cancer at the Department of Radiation Oncology of the UMC Utrecht since 2013. Since then, more than 200 patients with locally recurrent prostate cancer have been treated with focal salvage high-dose-rate brachytherapy (FS-HDR-BT).67 As mentioned in the introduction, focal treatment has become available due to significant developments and improvements in imaging, such as multiparametric MRI (mp-MRI) and prostatespecific membrane antigen positron emitting tomography CT (PSMA-PET/CT). For FS-HDR-BT treatment, MR imaging is used for verification of the brachytherapy catheters and for re-contouring of the target and OARs just prior to delivery of the HDR brachytherapy dose.67 Over the years, this treatment has shown promising results with respect to safety and toxicity, with 2-10% grade ³ 3 GU toxicity and no grade ³ 3 GI toxicity.68–73 On the other hand, oncological outcomes are less optimal, with 3-year bDFS rates of less than 50%.72–74 Current guidelines do not recommend specific salvage treatments for the treatment of isolated recurrence in case of biochemical failure after primary radiotherapy, since the available evidence is still weak with a lack of randomised clinical trials.75 There is a strong recommendation to only treat highly-selected patients with high-intensity focussed ultrasound (HIFU), cryotherapy or salvage brachytherapy within clinical trials or well-designed prospective studies.75 The risk of side effects should be carefully weighed against the potential benefit on an individual basis. To be able to better identify patients who are likely to benefit from single fraction FS-HDR-BT prior to treatment, we have therefore developed a baseline prediction model in chapter 8. The outcome we used was biochemical failure, which was defined as an increase in PSA of at least two points (+ 2.0 ng/mL) from the PSA nadir after salvage treatment (Phoenix definition). The results can be used in clinical practice – although preferably external validation is performed – to counsel patients. Furthermore, the results might be applicable to other focal salvage treatments as well. However, it is questionable to what extent the chosen outcome is relevant for the patient. The primary goal of focal salvage treatment is to postpone the initiation of androgen deprivation therapy (ADT) and other (toxic) systemic treatments such as chemotherapy. In a study by van Son et al.74, ADT-free survival was 90% after a median follow-up of 31 months. The increase in PSA level after salvage treatment can be worrying, but does not necessarily implicate that ADT should be initiated immediately. In most patients there are only signs of local recurrence on PSMA-PET/CT without metastatic disease at the time of biochemical failure.74 This opens up possibilities for re-salvage treatment.74,76 Watchful waiting can also be a ‘treatment’ strategy, as in some patients the PSA only tends to increase slowly over time without immediate signs of metastatic disease. In these patients, initiation of systemic treatment can be postponed, withholding them from the toxic systemic effects. Nevertheless, biochemical failure is associated with an increased risk of developing distant metastases, prostate cancer-specific mortality, and overall mortality.75 No consensus guidelines currently exist on the best approach in case of biochemical failure after salvage treatment, but there are recommendations for treatment of metastatic prostate cancer.75 11
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