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

Abstract

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, radiographic 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.

Keywords: Alpha-emitter; Bone scan; Bone-targeting radiopharmaceutical; Pain flare-up; Prostate-specific antigen.

Figure 1

Percentage of PSA Increase for 24 Patients From Pretherapy to End of Therapy. Empty Bars Represent Patients Who Developed Visceral Disease. Note That the Dotted Lines Represent 50% and −30% PSA Increase, Respectively. Data Are Not Available for 5 Patients Abbreviation: PSA = prostate-specific antigen.

Figure 2

Percentage of PSA Increase Between Each Consecutive Cycle. The Median Percentages of PSA Increase Are 17.95%, 16.56%, 15.37%, 9.88%, 9.37%, and 0.00%, Respectively, for Base and Cycle 1, Cycles 1 and 2, Cycles 2 and 3, Cycles 3 and 4, Cycles 4 and 5, and Cycles 5 and 6. The Right Boxplot Represents the Percentage of PSA Increase Between the Baseline and the Last Radium Therapy Where the Median Percentage of PSA Increase Is 95.68%. Note That the 50% and −30% PSA Increases Are Indicated by the Dotted Lines Abbreviation: PSA = prostate-specific antigen.

Figure 3

Boxplots With % PSA Increase in Patient Subgroups Abbreviation: PSA = prostate-specific antigen.

Figure 4

Bone Scan Images. Improving Bone Scan (A), Stable Bone Scan (B), and Worse Bone Scan (C)