Maarten van der Doelen

Chapter 8

measures as secondary endpoint, to assist in evaluating the risks and benefits of these cancer therapies. The trials showed that increased OS was accompanied with pain relief, improvement in patient-reported HR-QoL during therapy and a delay in HR-QoL deterioration and pain progression during follow-up. (37-42) However, PRO measures are not routinely assessed in daily uro-oncology practice and real-world studies on HR QoL of mCRPC patients receiving life-prolonging therapies, including radium-223, are scarce. Therefore, we conducted a multicenter, prospective observational cohort study to evaluate HR-QoL, psychological distress and fatigue in mCRPC patients treated with radium-223 ( chapter 4 of this thesis). Baseline HR-QoL, pain intensity, psychological distress and fatigue were worse in patients who did not complete radium-223 therapy. In patients who completed therapy, stabilization of HR-QoL was perceived and psychological distress and fatigue remained stable, whereas clinically meaningful and statistically significant deterioration of HR-QoL, psychological distress and fatigue over time was observed in patients who discontinued radium-223 therapy. A trajectory analysis of patterns in HR-QoL throughout radium-223 therapy revealed that HR-QoL deterioration over time was more likely in patients with opioid use, low hemoglobin and high alkaline phosphatase levels at baseline. There is no international consensus on the use of specific questionnaires for the different types and stages of cancer. In addition, there is also no guidance on specific evaluation methods of the different HR-QoL dimensions. For example, the PCWG3 guideline recommends to assess physical functioning using an established multi-item questionnaire such as the European Organization for Research and Treatment of Cancer (EORTC) core QoL questionnaire (QLQ-C30), but do not provide specific guidance for assessment of other HR-QoL domains (such as psychological and social aspects) and do not differentiate between non-metastatic (e.g. locally advanced) and metastatic castration-resistant prostate cancer. The various ways the HR-QoL measures are analyzed and interpreted make it difficult to compare results across trials, and hinders the application of research findings in clinical guidelines and health policy. (43) In our study, we used the EORTC QLQ-C30 and its bone metastases module (BM-22) to evaluate cancer-specific and bonemetastases-relatedHR-QoL in this study. Phase 3 trials mostly used the European QoL 5-Dimensions (EQ-5D) and the Functional Assessment of Cancer Therapy - Prostate (FACT-P) questionnaires to evaluate general QoL and prostate cancer related HR-QoL, respectively. (44) However, the EQ-5D and FACT-P questionnaires are not specifically designed for the mCRPC population and therefore, specific symptoms of this population might not have been addressed in the phase 3 trials. Both randomized clinical trials as well as observational real-world studies would

206