Maarten van der Doelen

Chapter 9

showed significantly longer overall survival (median overall survival 36.3 months versus 17.0 months, respectively) and more frequently completed radium-223 therapy (79% versus 57%, respectively). A multivariate model identified DNA damage repair mutation status as the only independent prognostic factor of overall survival in this group of patients. In the general discussion, chapter 8 , the outcomes of the studies described in this thesis are discussed and reviewed in a broader perspective. Furthermore, future possibilities and challenges on TAT in metastatic prostate cancer are described. Conclusions In conclusion, this thesis presented new insights in the treatment of metastatic prostate cancer patients with TAT. We showed that the effect of TAT may be evaluated by modern imaging techniques (e.g. 68 Ga-PSMA PET/CT), alternative biomarkers (circulating peripheral blood mononuclear cells) and quality of life measures. We found that completion of radium-223 therapy was associated with quality of life stabilization and longer overall survival when compared to patients who discontinued radium-223 therapy. Furthermore, we demonstrated that pretherapeutic variables that reflect less advanced mCRPC are the main prognosticators for the overall survival of mCRPC patients receiving radium-223 therapy. In addition, early changes in ALP levels may act as a prognostic marker for the overall survival in these patients. DNA damage repair alterations may be associated with enhanced efficacy of radium-223 therapy and longer overall survival of mCRPC patients.

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