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.
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).
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.
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.
JNCI cancer spectrum. 2023 Oct 03 [Epub ahead of print]
Chris Parker, Nina Tunariu, Holly Tovey, Roberto Alonzi, Matthew D Blackledge, Gary J R Cook, Sue Chua, Yong Du, Shaista Hafeez, Iain Murray, Anwar R Padhani, John Staffurth, Alison Tree, Helen Stidwill, Jessica Finch, Andra Curcean, Peter Chatfield, Sophie Perry, Dow-Mu Koh, Emma Hall
The Royal Marsden NHS Foundation Trust, London, UK., The Institute of Cancer Research, London, UK., Mount Vernon Cancer Centre, Northwood, UK., Cancer Imaging Department and King's College London and Guy's and St Thomas' PET Centre, King's College London, London, UK., Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, Northwood, UK., Velindre Cancer Centre, Cardiff, UK.