Radiographic and laboratory assessment of bone metastases in castration-resistant prostate cancer patients undergoing Radium-223 dichloride therapy

Objectives Radium-223 dichloride (Ra-223) is an FDA approved therapeutic radiopharmaceutical for treatment of patients with metastatic castrate resistant prostate cancer with bone metastases and no visceral metastases. However, at present, there is very sparse imaging data as to the effects of the Ra-223 treatment on the bone metastases of these patients. Our objective for this study is to assess the changes in the metastatic osseous lesions with Radium 223 treatment utilizing F-18 Sodium Fluoride (NaF) Bone PET/CT scans.

Methods This is an IRB approved retrospective study that included prostate cancer patients who underwent Ra-223 treatment at our institution. Details about the prostate cancer and prior treatments, Ra-223 treatment, lab values and F-18 NaF PET/CT scans was recorded and analyzed. Each patient had a baseline F-18 NaF Bone PET/CT scan as well as after 2 cycles and 6 cycles. Each patient also had CBC, serum chemistry profile including serum alkaline phosphatase (ALP) and prostate specific antigen (PSA) prior to each Radium 223 cycle. Index lesions were identified on the baseline F-18 NaF Bone PET/CT scans and their SUVmax as well as HUavg were recorded. These were followed on subsequent F-18 NaF Bone PET/CT scans. Findings were correlated with clinical and laboratory parameters.

Results 13 patients were identified of which 5 were excluded as they could not complete all 6 cycles for disease progression and did not have adequate data to be included in study analysis. All remaining 8 patients were able to complete all 6 cycles of therapy and had adequate laboratory and imaging data. PSA response was highly variable with no statistically significant discernable trend. ALP levels consistently dropped with each Ra-223 treatment, unless there was obvious significant disease progression (as seen in patients who had to stop treatment and were excluded from the study). The F-18 NaF bone PET/CT scans generally showed improvement in the lesions with decrease in intensity of NaF uptake and increase in density on CT. The improvement was most obvious on the scan after 6 cycles of treatment. On the scan after 2 cycles of treatment, the findings were not significantly changed in 5 patients. In 3 patients, the lesions appeared somewhat more prominent, but the patients did not report any increased pain and ALP levels were trending down. These lesions eventually improved on the scan after 6 cycles. All 8 patients reported improvement in pain.

Conclusions F-18 NaF Bone PET/CT scans could potentially be a useful modality to assess treatment response in bone metastases following treatment with Radium 223, correlating with ALP activity. There is potential for “imaging flare phenomenon” initially during the course of treatment. Whether these patients respond better to Radium 223 therapy needs further assessment with larger prospective trials.