Radium-223 in Heavily Pretreated Metastatic Castrate-Resistant Prostate Cancer

An increasing prostate-specific antigen (PSA) level during radium therapy for metastatic castrate-resistant prostate cancer (mCRPC) is not an uncommon phenomenon, especially in heavily pretreated patients; however, an increasing PSA level does not always indicate progressive disease. Bone scan, chest and abdomen imaging should be performed to determine the cause of PSA increase, which could be true disease progression in the form of new visceral metastasis or flare reaction. Background: Radium-223 is a bone-targeting radiopharmaceutical that extends survival in mCRPC. Postapproval data are limited, and the value of biochemical and radiologic monitoring during radium therapy is unknown. Patients and Methods: We conducted a retrospective study of 29 patients with mCRPC who received radium-223 at 1 of 3 participating institutions between August 2013 and December 2014. Trend of PSA, radiographid changes, and association of biochemical and clinical variables with PSA trend were measured. Results: The median age of patients was 70 years, 79% of patients (N = 23) were European Americans, and 17% of patients (N = 5) were African Americans. Twenty patients (69%) had received at least 3 lines of prior therapies. Some 38% of patients (N = 11) received all 6 cycles of radium-223. Twenty patients (69%) had an increase in PSA during radium therapy, and 4 patients (14%) had a decline in PSA levels. Five patients had visceral metastases on computed tomography imaging performed during the course of radium-223. Conclusions: Radium therapy in mCRPC was associated with an increase in PSA in the majority of these heavily pretreated patients. The development of visceral disease was not uncommon, suggesting a need for follow-up computed tomography monitoring during radium-223 therapy. The significance of early increases in PSA and pain with radium-223 is still uncertain. Although pain and PSA flare have been reported in patients who subsequently have a dramatic response to therapy, we observed that a PSA increase or pain flare correlates to an improvement in bone scans only in a minority of patients.