Radium-223 in metastatic castration resistant prostate cancer: whole body diffusion-weighted MRI to assess response.

BACKGROUND: Radium-223 is a bone-seeking, alpha-emitting radionuclide used to treat men with bone metastases from castration resistant prostate cancer (mCRPC). Sclerotic bone lesions are non-evaluable by RECIST. There is a need for imaging response biomarkers. METHODS: We did a phase II randomised trial to assess disease response to radium-223. Men with mCRPC and bone metastases were randomly allocated 55 or 88kBq/kg radium-223 every 4 weeks for 6 cycles. Whole body MRI with diffusion-weighted imaging (WBMRI) was done at baseline, cycle 2 and 4, and post-treatment. Primary endpoint was defined as 30% increase in global median apparent diffusion coefficient (ADC). RESULTS: Disease response on MRI was seen in 14/36 evaluable patients (39%; 95%CI: 23-56%), with marked inter- and intra-patient heterogeneity of response. There was an association between PSA response and MRI response (Odds ratio 18.5; 95% CI: 1.32-258, p = 0.013). Mean administered activity of radium-223 per cycle was not associated with global MRI response (p = 0.216) but was associated with MRI response using a 5 target lesions evaluation (p = 0.007). In 26/36 (72%) patients, new bone metastases, not present at baseline, were seen on MRI during radium-223 treatment. CONCLUSIONS: WBMRI is useful for assessment of disease response in bone. Response to radium-223 is heterogeneous, both between patients and between different metastases in the same patient. New bone metastases appear during radium-223 treatment.The REASURE trial is registered under ISRCTN17805587