Review of Radium-223 and Metastatic Castration-Sensitive Prostate Cancer

Abstract

Background: Radium-223 is approved for treatment of bone metastases in metastatic castration-resistant prostate cancer (mCRPC). After the ALSYMPCA trial showed overall survival benefit with the addition of radium-223 to standard of care in mCRPC in 2013, there have been numerous publications and trials using radium-223 in mCRPC. Recently, there has been interest in using radium-223 earlier in the metastatic prostate cancer timeline, in metastatic castrate-sensitive prostate cancer (mCSPC); however, currently, radium-223 in mCSPC treatment is investigational. Aim: A literature search was conducted to review the use of radium-223 in mCSPC treatment from 1980 to 2019. A review of both radium-223 articles and abstracts was performed. Search terms included metastatic prostate cancer and radium-223, mCSPC, hormone-sensitive metastatic prostate cancer, radium-223, and oligometastatic disease. The results were limited to studies involving multiple patients with mCSPC. Conclusion: There are a limited number of studies of radium-223 in mCSPC treatment and the authors report on these studies (two published studies and four ongoing trials). Trials are currently underway to assess if radium-223 could be used in mCSPC as a treatment for bone metastases and micrometastases. Future data from these trials will be informative as to the benefit of radium-223 in mCSPC treatment and may change treatment paradigms for mCSPC. This review will focus on trials assessing the role of radium-223 in mCSPC.

Towards Routine Clinical Use of Dosimetry in [177Lu]Lu-PSMA Prostate Cancer Radionuclide Therapy: Current Efforts and Future Perspectives

“…By lessening the localized dose pattern with higher energy beta electrons to achieve uniformity [109], or chelating PSMA molecules with radioisotopes, such as alpha emitters, capable of causing greater DNA damage through high LET emission [110], radiation dose delivery may be optimized. While 223RaCl is the first and only alpha emitting radioligand currently FDA and European Medicines Agency (EMA) approved for mCRPC with bone metastases with no known extra-skeletal metastases [111,112,113], radionuclides such as 149 Tb, 211 At, 213 Bi, 212 Pb/ 212 Bi, 227 Th, and 225 Ac are being evaluated for their use in PSMA RNT preclinical and clinical studies [114,115,116,117,118]. The dosimetry of the latter three radionuclides for RNT in prostate cancer patients is being investigated with both PSMA and other chelators [119,120,121,122,123,124,125,126,127].…”

Research Progression in the Mechanism of Bone Metastasis and Bone-Targeted Drugs in Prostate Cancer

“…223Ra is a calcium analogue that is absorbed into bone by osteoblasts through the same pathway as calcium, and decays to produce alpha particles after binding with bone, causing cytotoxic double-strand breaks (DSBs) in neighboring tumor cells and inducing apoptosis [69][70][71][72][73]. In the phase III clinical trial ALSYMPCA [74], patients treated with 223Ra had an average of 3.6 months better overall survival (OS) than those treated with placebo, and patients treated with 223Ra had a significant reduction in SREs and demonstrated a better quality of life.…”

DNA Damage by Radiopharmaceuticals and Mechanisms of Cellular Repair

“…Given their high energy, ranging from 4 to 8 MeV, and short emission range in body tissues, a targeted radiopharmaceutical radiolabeled with an α-emitter can lead to high-energy deposition within the tumor while minimizing radiation to the surrounding non-diseased host tissues [ 39 , 40 , 41 ]. Radium-223 dichloride ( 223 RaCl 2 , Xofigo) is the first approved targeted α-RPT by both the FDA and the European Medicines Agency (EMA) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases [ 42 , 43 , 44 , 45 ]. Patients treated with 223 RaCl 2 have shown significantly improved overall survival (OS) and delayed symptoms from osseous metastases [ 46 , 47 ].…”