Metastatic castrate-resistant
prostate cancer (CRPC) refers to the disease state in which metastatic
prostate cancer fails to respond to
androgen deprivation
therapy (ADT). This can be manifest as a rising PSA, increase in radiographically measurable disease, or progression of clinical disease. Roughly 90 % of men with metastatic
prostate cancer have bone
metastases, which is a predictor of both morbidity and mortality. Historically, treatment has been palliative, consisting of external beam
radiation therapy (EBRT) and pharmacological
analgesics for
pain control and osteoclast inhibitors, such as
bisphosphonates and
denosumab to mitigate skeletal-related events. Older
radiopharmaceuticals, such as
Strontium-89 and
Samarium-153, are Beta-emitting agents that were found to provide palliation but were without survival benefit and carried high risks of myelosuppression.
Radium-223 is an Alpha-emitting
radiopharmaceutical that has demonstrated a significant overall survival benefit in men with metastatic CRPC, delay to symptomatic skeletal events (SSEs), and improvement in
pain control, with a favorable toxicity profile compared with placebo. Unlike EBRT,
Radium-223 has systemic uptake, with the potential to address several bone
metastases concurrently and provides overall survival benefit. It is a simple administration with minimal complexity and shielding requirements in experienced hands. EBRT appears to provide a more rapid and dramatic palliative benefit to any given lesion. Because
Radium-223 has limited myelosuppression, the two can be thoughtfully integrated, along with multiple agents, for the treatment of men with CRPC with symptomatic bone
metastases. Given its excellent safety profile, there is interest and anecdotal safety combining
Radium-223 with
therapies, such as
abiraterone and
enzalutamide. Formal recommendations regarding combination
therapies will require clinical trials. The use of Alpha-emitting
radiopharmaceuticals in castrate-sensitive disease, in metastatic asymptomatic CRPC, the categorical sequencing amongst other treatments for CRPC, as well as the application to other primary pathologies, such as metastatic
breast cancer, is currently evolving.