Radium-223-dichloride in osseous metastatic prostate carcinoma in routine clinical practice

There are numerous therapeutic approaches for the treatment of bone metastases in osseously metastasised prostate carcinoma. These include bisphosphonates or denosumab as well as radiopharmaceuticals such as strontium and samarium. In contrast to these, Ra-223 is the only radiopharmaceutical that leads to a significant prolongation of life. It is only slightly myelotoxic and the side effect rates are manageable. This study investigated the efficacy and safety profile of Ra-223 therapy in 46 patients with osseous metastatic castration-resistant prostate cancer. Treatment response was analysed by PSA and AP progression, pain intensity as assessed by pain questionnaires, and skeletal scintigraphy and SPECT/CT acquisitions. This study was also the first to use SUVmax as a quantitative marker in SPECT/CT to analyse treatment response. The safety profile was assessed by blood value changes as well as non-haematological side effects. Of the 46 patients, 29 patients (63%) received all six cycles and 17 patients (37%) discontinued therapy. Of the 29 patients who received all six cycles of Ra-223 therapy, 11 patients (38%) experienced a decrease in PSA and 18 patients (62%) experienced an increase in PSA during therapy. Alkaline phosphatase decreased in 22 patients (76%) and increased in 5 patients (17%) by cycle 6. Analysis of the mean values from the pain questionnaires showed a decrease in pain intensity. Of the 17 patients who completed the questionnaires, 8 patients experienced a decrease in pain during therapy and 7 patients experienced an increase in pain. 2 patients described a constant pain intensity. Visual analysis of skeletal scintigraphy acquisitions showed stable findings in 9 patients (31%), treatment response in 7 patients (24%), progression in 9 patients (31%) and mixed response in 2 patients (7%). 2 patients (7%) did not receive imaging at follow-up. The mean SUVmax values of bone metastases decreased in all but 3 patients. A correlation between SUVmax and visual findings on skeletal scintigraphy was demonstrated (p = 0.018). All blood values decreased continuously during the therapy; the lymphocyte values were particularly strongly affected. However, according to the CTCAE criteria, there was not a single case of grade 4 toxicity and only one case of grade 3 anaemia, 7 cases of grade 3 lymphopenia and one case of grade 3 neutropenia. Consequently, most patients had only a discrete drop in blood counts. Therapy-associated adverse events occurred in 24 patients (52%), the most common being nausea (N = 6, 13%), loss of appetite (N = 8, 17%) and diarrhoea (N = 6, 13%), as well as ostealgia (N = 8, 17%) and fatigue (N = 6, 13%). In addition to those patients who benefited very well from Ra-223 therapy, there were also some who experienced significant progression during therapy. An individual decision on the respective suitable therapy procedure for the patients in advance is obligatory, but further studies are still necessary for this.