Symptomatic Skeletal Benefits with Radium-223 Prostate Cancer Treatment

Prostate cancer patients with bone metastases are less likely to experience symptomatic skeletal events when treated with radium-223

medwireNews: Radium-223 dichloride significantly reduces the risk of symptomatic skeletal events in patients with castration-resistant, metastatic prostate cancer, the ALSYMPCA trial shows.

The research, published in The Lancet Oncology, follows results from the phase III randomised trial that demonstrated improved overall survival for patients given radium-223 compared with placebo-treated controls.

The current report “further establishes the clinical benefits of radium-223 and provides valuable information to guide treatment decisions for patients with metastatic castration-resistant prostate cancer”, say Oliver Sartor, from Tulane Medical School in New Orleans, Louisiana, USA, and co-authors.

Overall, 33% of the 614 patients given radium-223 developed a first symptomatic skeletal event requiring external beam radiation, compared with 38% of 307 placebo-treated controls, with a significant difference in the median time to these events, at 15.6 versus 9.8 months.

Patients given radium-223 were also significantly less likely to require external beam radiotherapy for bone pain (hazard ratio [HR]=0.67) or experience spinal cord compression (HR=0.52) than controls, although there was no significant impact on the risk of symptomatic pathological fracture, or the need for orthopaedic surgery for tumour events. All patients had two or more bone metastases but no visceral spread and had either previously been treated with, or were not eligible for, docetaxel.

In an accompanying comment, Christopher Logothetis, from the University of Texas in Houston, USA, praises the ALSYMPCA trial investigators for choosing patients likely to benefit from radiopharmaceutical treatment and for following up with clinical events rather than routine imaging.

“As a result of this study, a new and safe method has been added to the inventory of available effective agents for advanced prostate cancer”, he writes, establishing “a new therapeutic paradigm by confirming the merits of bone targeting in men with advanced prostate cancer.”

The lack of dose-limiting haemotoxicity or a proportional decrease in serum prostate-specific Antigen (PSA) during radium-223 treatment raises “intriguing questions” on how the treatment works, observes Christopher Logothetis.

“An urgent need exists to identify, and build on, the mechanisms that explain the clinical efficacy of these agents, to identify predictive and companion markers that can be used to select who will benefit from radium-223, and to continue to monitor its efficacy”, he concludes.


Sartor O, Coleman R, Nilsson S, et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol 2014; Early Online Publication 14 May. doi:10.1016/S1470-2045(14)70183-4

Logothetis C. Prostate cancer bone metastases: not so systemic after all. Lancet Oncol 2014; Early Online Publication 14 May. doi:10.1016/S1470-2045(14)70217-7

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