Our study is a phase II randomised study of stereotactic body radiotherapy with or without radium-223 for men with oligometastatic hormone sensitive prostate cancer.
What was the study design?
This was a randomised multicentre open-label phase II design and patients were randomised 1:1 to receive stereotactic body radiotherapy to all visible lesions up to 5 on molecular imaging or up to 3 on conventional imaging versus receiving the stereotactic body radiotherapy along with up to six cycles of radium-223 given once monthly.
What were the results of this study?
This study showed that there was no significant delay in progression of disease with the addition of radium-223 to stereotactic body radiotherapy in bone metastatic, oligometastatic castrate sensitive prostate cancer.
What is the significance of these results?
The significance of this is that in the context of radium demonstrating benefit in studies of higher volume disease, this may show us what the lower limit of radium’s mechanism of action is able to provide benefit. So, for example, in the ALSYMPCA study with symptomatic higher volume bone metastatic prostate cancer in the castrate resistant setting in combination with ADT there was benefit to radium-223. In this study the radium really would only be impacting the microscopic disease that was not already treated with stereotactic body radiotherapy and therefore, due to the mechanism of action, radium-223 requiring as a calcium mimetic areas of bone turnover in order to be targeted to the lesions, it was not effective. However, in the clinical context of other radiopharmaceuticals being investigated with molecular targeting, such as PSMA targeted therapies, there is potential that those may be effective in this setting even though radium-223 did not delay progression.
Is there anything else you would like to add?
This study also had a number of interesting biological correlates that did have positive results. We validated a high-risk mutational signature as prognostic in this subset of patients and also a T-cell receptor repertoire as a prognostic biomarker for oligometastatic castrate sensitive prostate cancer. This extends the importance of these two biomarkers in this disease setting.
