Maarten van der Doelen

General discussion and future perspectives

benefit from an internationally accepted guideline providing standards for collecting and reporting PRO data and the analysis and interpretation of PRO endpoints in clinical trials. (43) Furthermore, no advice regarding the minimally important differences or clinically relevant changes for the analysis of the Hospital Anxiety and Depression Scale (HADS) and the Checklist Individual Strength - Fatigue subscale (CIS-F) questionnaires was available for our mCRPC population. We adapted the minimal important difference cut-offs from a study using the HADS in patients with chronic obstructive pulmonary disease. However, for the CIS-F, no minimal important difference cut-off was available in literature. The development of specific cut-offs for minimal important differences for the mCRPC population would strengthen the analysis of the HADS and CIS-F in the future. PART II: PROGNOSTIC PARAMETERS IN PATIENTS TREATED WITH TARGETED ALPHA-RADIONUCLIDE THERAPIES Post registration reports on the use of radium-223 in the real-world populations demonstrated that appropriate selection of patients for radium-223 therapy is challenging. Several large retrospective studies provided evidence that the OS benefit in daily practice appears to be less than reported in the ALSYMPCA study. (45-47) Patients may derive less benefit from radium-223 either due to selection of patients with poorer prognostic clinical characteristics, or because radium-223 is not optimally sequenced with an armamentarium of drugs including abiraterone, enzalutamide, docetaxel and cabazitaxel. Therefore, knowledge of pretherapeutic prognostic factors can lead to better patient selection for radium-223 therapy, in order to optimize the outcomes of treatment. Clinicopathologic prognostic parameters In chapter 5 of this thesis, we aimed to identify pretherapeutic variables associated with OS in mCRPC patients treated with radium-223 therapy in an academic care study population. We identified a large difference in OS between patients who completed and discontinued radium-223 therapy; patients who completed radium-223 therapy had a median OS of twenty months, while patients who received one to five radium-223 injections had a median OS of only six months. We found that good Eastern Cooperative OncologyGroup (ECOG) performance status and low lactate dehydrogenase (LDH) levels at baseline were significantly associated with longer OS. In fact, these characteristics

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