Evaluating radium-223 response in metastatic castration-resistant prostate cancer with imaging

Radium-223 is a first-in-class targeted alpha therapy indicated for treating bone metastases from metastatic castration-resistant prostate cancer (mCRPC) without visceral metastases. Imaging plays an important role in the selection of patients eligible for radium-223 therapy. In the ALSYMPCA trial protocol, bone scintigraphy was used to detect lesions, essentially osteoblastic bone metastases, whereas computed tomography (CT) was used to exclude visceral metastases, with no interim imaging until treatment completion unless clinically indicated. Yet, questions remain: How can we monitor treatment progress more closely and evaluate treatment response more precisely? In the cases discussed herein, interim evaluation of response to radium-223 showed discordance between bone scintigraphy and F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in the patterns of bone lesions observed, that is more lesions were detected on PET/CT. It is postulated that the additional lesions may be attributed to bone marrow metastases that were not effectively targeted by radium-223 as its alpha radiation do not reach deep into the bone marrow. Although the clinical significance of the discordance requires further clarification, it makes sense to consider radium-223 early on in the course of mCRPC, when marrow involvement is minimal, so as to optimize treatment outcomes.