ALSYMPCA
Radium-223 was the first alpha-emitter to improve survival, the trial behind Xofigo
Quick Answer
ALSYMPCA (Parker et al., N Engl J Med 2013) was the phase 3 randomized trial that established ²²³Ra-dichloride — a bone-seeking alpha emitter — for metastatic castration-resistant prostate cancer with symptomatic bone metastases and no visceral disease. It improved overall survival and delayed symptomatic skeletal events, making Ra-223 the first alpha-particle therapy to demonstrate a survival benefit in a randomized trial and supporting the approval of Xofigo.
The trial
Design: phase 3, 921 patients with mCRPC, symptomatic bone metastases, and no known visceral metastases. Randomized 2:1 to ²²³Ra-dichloride (50 kBq/kg IV every 4 weeks × 6; current calibration standard is 55 kBq/kg) plus best standard of care versus placebo plus best standard of care. Primary endpoint: overall survival.
Key result
²²³Ra improved overall survival (~14.9 vs 11.3 months; HR ≈ 0.70) and delayed symptomatic skeletal events, with a favorable safety profile — its very short alpha range concentrates dose at the bone–tumor interface with relatively limited marrow toxicity. Because the dose is deposited in bone, PSA is not a reliable response marker; alkaline phosphatase and clinical/skeletal endpoints are used instead.
Why it mattered
ALSYMPCA proved that a targeted alpha emitter could prolong survival, opening the field of alpha therapy and giving bone-dominant mCRPC a life-prolonging radionuclide option. It remains the standard radionuclide therapy for symptomatic, bone-dominant mCRPC without visceral disease.
Context & caveats
Ra-223 treats the bone microenvironment, not nodal or visceral disease. The later ERA-223 trial showed more fractures and deaths when Ra-223 was combined with abiraterone + prednisone, so that combination is avoided and a bone-health agent is ensured. Sequencing with other marrow-affecting therapies (e.g. ¹⁷⁷Lu-PSMA) requires attention to cumulative marrow dose.
Self-Check
Q1. What did ALSYMPCA establish, and why is it historically significant?
Answer: That ²²³Ra-dichloride improves overall survival in symptomatic bone-metastatic mCRPC without visceral disease — the first alpha-emitter therapy with a randomized survival benefit.
Q2. What were the survival results and the exact indication?
Answer: OS ~14.9 vs 11.3 months (HR ≈ 0.70); indication is mCRPC with symptomatic bone metastases and no known visceral disease.
Q3. Why is PSA not used to monitor Ra-223 response?
Answer: The alpha dose is deposited at the bone–tumor interface, not throughout soft-tissue disease, so PSA may rise despite benefit; follow alkaline phosphatase and clinical/skeletal endpoints.
Q4. What combination is avoided based on a later trial, and which trial?
Answer: Ra-223 + abiraterone/prednisone — the ERA-223 trial showed more fractures and deaths; ensure a bone-health agent instead.
Key References
- Parker C, et al. Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer (ALSYMPCA). N Engl J Med 2013;369:213–223. doi:10.1056/NEJMoa1213755
Evidence & sources
https://nuc.med/alsympca-trial/ Report an issue