Radium-223 in metastatic castration-resistant prostate cancer: whole-body diffusion-weighted magnetic resonance imaging scanning to assess response.

BACKGROUND: Radium-223 is a bone-seeking, ɑ-emitting radionuclide used to treat men with bone metastases from castration-resistant prostate cancer. Sclerotic bone lesions cannot be evaluated using Response Evaluation Criteria in Solid Tumors. Therefore, imaging response biomarkers are needed. METHODS: We conducted a phase 2 randomized trial to assess disease response to radium-223. Men with metastatic castration-resistant prostate cancer and bone metastases were randomly allocated to 55 or 88 kBq/kg radium-223 every 4 weeks for 6 cycles. Whole-body diffusion-weighted magnetic resonance imaging (DWI) was performed at baseline, at cycles 2 and 4, and after treatment. The primary endpoint was defined as a 30% increase in global median apparent diffusion coefficient. RESULTS: Disease response on DWI was seen in 14 of 36 evaluable patients (39%; 95% confidence interval = 23% to 56%), with marked interpatient and intrapatient heterogeneity of response. There was an association between prostate-specific antigen response and MRI response (odds ratio = 18.5, 95% confidence interval = 1.32 to 258, P = .013). Mean administered activity of radium-223 per cycle was not associated with global MRI response (P = .216) but was associated with DWI response using a 5-target-lesion evaluation (P = .007). In 26 of 36 (72%) patients, new bone metastases, not present at baseline, were seen on DWI scans during radium-223 treatment. CONCLUSIONS: DWI 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.

Fracture Risk in Men with Metastatic Prostate Cancer Treated With Radium-223.

BACKGROUND: Radium-223 is a bone-seeking, alpha-emitting radionuclide used in metastatic castration-resistant prostate cancer (mCRPC). Radium-223 increases the risk of fracture when used in combination with abiraterone and prednisolone. The risk of fracture in men receiving radium-223 monotherapy is unclear. PATIENTS AND METHODS: This was a prospective, multicenter phase II study of radium-223 in 36 men with mCRPC and a reference cohort (n = 36) matched for fracture risk and not treated with radium-223. Bone fractures were assessed using whole-body magnetic resonance imaging. The primary outcome was risk of new fractures. RESULTS: Thirty-six patients were treated with up to six 4-week cycles of radium-223. With a median follow-up of 16.3 months, 74 new fractures were identified in 20 patients. Freedom from fracture was 56% (95% confidence interval, 35.3-71.6) at 12 months. On multivariate analysis, prior corticosteroid use was associated with risk of fracture. In the reference cohort (n = 36), 16 new fractures were identified in 12 patients over a median follow-up of 24 months. Across both cohorts, 67% of all fractures occurred at uninvolved bone. CONCLUSIONS: Men with mCRPC, and particularly those treated with radium-223, are at risk of fracture. They should receive a bone health agent to reduce the risk of fragility fractures.