Maarten van der Doelen

Chapter 1

In addition to biochemical and radiological responses, patient-reported outcomes are important in the evaluation of therapies. Patient-reported outcomes can inform health care professionals on the efficacy and tolerability of treatment, increase patient satisfaction, improve symptom control, and provide prognostic information. (54) Patient selection for targeted alpha-radionuclide therapies TheALSYMPCA trial benchmarked the criteria for patients to receive radium-223 therapy. These criteria necessitate progressive CRPC with symptomatic bone metastases, with bone-only disease, or with concomitant lymph node metastases with a largest diameter less than 3 cm on the short-axis, no (history of ) visceral metastases, no imminent or established spinal cord compression, and adequate hematological, liver and kidney function. (23) However, in the ALSYMPCA trial, a statistically significant OS benefit of treatment could not be demonstrated in some subgroups, including patients with low baseline alkaline phosphatase levels (< 220 U/L), Eastern Cooperative Oncology Group performance score ≥ 2 and very low or extremely high number of bone metastases on baseline bone scintigraphy. (23) These findings raise the question whether radium-223 should be used in these subgroups. To evaluate the efficacy of radium-223 in patients with these characteristics, largeobservational studieswith real-worlddataarewarranted. Earlier utilization of radium-223 therapy in castrate-resistant state is more likely to result in completion of therapy and potentially better patient outcomes, partly because in later disease stage, patients exhibit more symptoms and are more likely to experience disease progression as a result of more aggressive cancer biology following resistance to antihormonal drugs and taxane-based chemotherapy. (55) In addition, radium-223 therapy should be withheld in patients with (a history of ) visceral metastases, necessitating baseline CT of thorax, abdomen and pelvis to exclude visceral disease and disease progression in lymph node metastases before initiation of radium-223. Particularly when radium-223 is initiated after one line of second-generation hormonal therapy and after docetaxel chemotherapy, the prevalence of baseline visceral metastases increases. (55, 56) This again underlines the importance of early initiation of radium-223 in the treatment paradigm of mCRPC. In the ALSYMPCA trial, symptomatic bone metastases were defined as bone metastases in patients who either use regular analgesic medication for cancer-related bone pain or receive external-beam radiation therapy for bone pain prior to initiation of radium-223. (23) Experiencing pain without daily use of analgesics or deriving a limitation in the performance of daily (strenuous) activities may also be considered as symptomatic disease, and these patients therefore should be considered as potential candidates for

16