Maarten van der Doelen

Chapter 8

cessation of radium-223 therapy. (85) Therefore, prospective assessment with a MRI of the spine must be considered in patients with diffuse bone metastatic disease prior to initiation of radium-223 therapy. Although 68 Ga-PSMA PET/CT and whole body MRI are readily available in many West European countries, these modalities have not been validated yet for the stratification and monitoring of therapies in mCRPC patients. The incorporation of new imaging techniques into clinical practice, such as PSMA-targeting PET/CT and whole body MRI, is essential to improve patient selection and treatment evaluation in the future. Radium-223 therapy in metastatic hormone-sensitive prostate cancer At present, radium-223 therapy is registered for application in mCRPC patients only. Recent studies have shown that the addition of local radiation therapy or systemic agents (docetaxel, abiraterone or enzalutamide) to androgen deprivation therapy (ADT) resulted in improved OS in patients with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC). (87-94) Therefore, it is hypothesized that radium-223 might also be effective already earlier in the metastatic prostate cancer timeline. Thus far, a limited number of studies have described the potential of radium-223 as a treatment for patients with newly diagnosed bone mHSPC. Two small studies analyzed the combination of radium-223 and ADT in mHSPC patients having multiple bone metastases and found this combination therapy to be safe and well tolerated. (95, 96) Moreover, one of these studies found a reduction in 18 F-NaF PET/CT uptake after three injections of radium-223. (95) In the prospective, single arm, open label phase 1/2 ADDRAD trial, radium-223 plus concurrent external beam radiation therapy to prostate and pelvic lymph nodes was combined with ADT in newly diagnosed bone mHSPC patients who had completed upfront docetaxel chemotherapy. (97) The combination of therapies was feasible andwell tolerated, with known toxicity of pelvic radiotherapy and the individual agents. Ninety percent of the patients experienced an ALP reduction and 80% of the patients showed stable or reduced tumor burden on whole body MRI scans. Despite these encouraging findings, a randomized, double-blind, phase 3 clinical trial will be necessary to investigate whether the addition of radium-223 to ADT is beneficial in patients with de novo mHSPC. Another potential indication for radium-223 therapy is the patient population with mHSPC and oligometastases to the bone after prior treatment of localized prostate cancer. In recent years, metastasis-directed therapy (MDT) with stereotactic ablative radiation (SABR) of a limited amount (3-5) of metastatic foci has gained attention after positive outcomes with regard to progression-free survival and ADT-free survival. (98,

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