Abstract

More than 90% of men with metastatic castrate resistant prostate cancer (mCRPC) have bone metastases, often as the only significant metastatic site. Bone metastases in prostate cancer can result in pain, pathological fracture, metastatic spinal cord compression and are the leading cause of prostate cancer mortality.

Bone targeted therapy in prostate cacner has included bone-seeking radionuiclides for nearly 30 years. The beta-emitting bone-seeking radionuclides Strontium-89 and  Samarium-153 EDTMP as well as Rhenium-186 HEDP and Rhenium-188 HEDP have been used to palliate pain in advanced cancer metastatic to bone for many years. Despite clear evidence of benefit in palliation, these agents have never been shown to result in a survival benefit for patients.

Radium-223 is the first in class alpha-emitting radionuclide which began clinical testing nearly 10 years ago and has recently been licenced for the treatment of symptomatic castration resistant prostate cancer (CRPC) metastatic to bone. In an international prospective randomised clinical trial, Radium-223 (50kBq/kg, for 6 cycles at 4 weekly intervals) + best standard of care (BOS) was shown to improve overall survival compared to placebo + BOS in men with symptomatic, metastatic CRPC. Radium-223 also resulted in significant improvement in time to symptomatic progression. Radium-223 was very well tolerated with very few serious toxicities recorded.

The rationale for using bone-targeted radionuclide therapy in CRPC will be discussed along with postulation on the likelihood of combination therapies using Radium-223. Because Radium-223 will be widely used in a very common cancer, there are opportunities for the development of the field of radionuclide therapy including the use of dosimetry-led prescribing of radionuclide.