FDA Approval: Radium-223 (Xofigo) for Prostate Cancer

The approval, in one line

On 15 May 2013 the FDA approved Xofigo, the brand name for radium Ra 223 dichloride, under New Drug Application 203971. The sponsor was Bayer HealthCare Pharmaceuticals.

The approval letter states the indication exactly: "the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease."

Three conditions are packed into that phrase. The cancer must no longer respond to hormone treatment. It must have spread to bone and be causing symptoms. And it must not be known to have spread to organs such as the liver or lung.

Why calcium chemistry is the whole idea

Radium-223 is an alpha emitter. Alpha particles are heavy and highly damaging, but they travel almost no distance.

NCI explains the mechanism plainly. Radium behaves as a calcium mimetic. Like calcium, it collects in bone that is remodeling rapidly — which is exactly what bone around a metastasis is doing. Once there, it emits radiation that travels less than 100 microns, about four one-thousandths of an inch. That short range is what limits damage to nearby healthy tissue.

The result is radiation delivered by the body's own mineral handling, rather than aimed from outside. Our overview of radiation therapy covers how external beam treatment differs.

The regimen is six intravenous injections, one every four weeks, dosed at 50 kBq per kilogram of body weight.

What ALSYMPCA showed

The evidence was ALSYMPCA, a phase 3, randomized, double-blind, placebo-controlled trial in 921 men.

Everyone had metastatic castration-resistant prostate cancer with bone spread. All had either received docetaxel chemotherapy, been ineligible for it, or declined it. They were assigned 2 to 1 to radium-223 or matching placebo. Both groups also received best standard of care.

The primary endpoint was overall survival.

At the planned interim analysis, covering 809 patients, median overall survival was 14.0 months with radium-223 and 11.2 months with placebo. The hazard ratio was 0.70, with a 95% confidence interval of 0.55 to 0.88 and a two-sided p-value of 0.002.

An updated analysis of all 921 patients confirmed it: 14.9 months versus 11.3 months, hazard ratio 0.70.

The trial was stopped early for efficacy at the interim analysis.

Time to the first symptomatic skeletal event also favored radium-223. That endpoint matters as much as survival here, because a fracture or spinal cord compression is what patients actually feel.

What it costs

This is a comparatively gentle drug for its class, which is part of why it was noticed.

The 2013 label lists the adverse reactions occurring in 10% or more of patients: nausea, diarrhea, vomiting, and swelling in the limbs. The most common laboratory abnormalities were anemia, low lymphocytes, low white cells, low platelets, and low neutrophils.

One number is worth reading carefully. Grade 3 and 4 adverse events were reported in 57% of the radium-223 group and 63% of the placebo group. The higher figure is in the placebo arm, which reflects how sick this population is.

The label's single warning section is bone marrow suppression. It directs blood counts before starting and before every dose, and says to stop if blood counts do not recover within six to eight weeks.

When to get checked

Most prostate cancer causes nothing at first. NCI notes that in the United States most cases are diagnosed through screening, so symptoms are uncommon at diagnosis.

When local symptoms do appear, NCI lists trouble starting urine flow, frequent urination especially at night, trouble emptying the bladder, and a weak or stop-and-go stream. Those are more often benign prostatic hyperplasia, an enlarged but non-cancerous prostate, than cancer.

The advanced-stage list is different and more urgent. NCI names back, hip, or pelvic pain that does not go away, and shortness of breath, deep fatigue, fast heartbeat, dizziness, or pale skin caused by anemia.

For anyone already living with prostate cancer that has spread to bone, one symptom needs same-day attention: new back pain with weakness, numbness, or difficulty controlling the bladder or bowel. That combination can mean pressure on the spinal cord, and treating it early protects function.

Whether to have a PSA blood test at all is a decision to make with a clinician, weighing early detection against finding cancers that would never have caused harm. Our page on prostate cancer sets out both sides.

The population this drug serves

For 2026 the American Cancer Society estimates about 333,830 new prostate cancer diagnoses and 36,320 deaths in the United States; SEER, which NCI runs as a surveillance program, carries the same projection. The median age at diagnosis is 68.

Most is caught early: 69% is localized and 14% regional at diagnosis. Five-year relative survival for both of those groups is essentially 100%.

Nine percent is distant at diagnosis, and five-year relative survival in that group is 40.1%. Across all stages it is 98.2% for men diagnosed from 2016 through 2022.

That headline figure of 98.2% is one of the most misread numbers in oncology. It is dominated by the large early-stage group. It does not describe the men ALSYMPCA enrolled, and it does not forecast any individual course. Our page on metastatic cancer explains what distant spread means.

What this approval cannot tell you

The indication is a boundary, not a suggestion. Known spread to organs outside bone puts a patient outside it.

ALSYMPCA also compared radium-223 against placebo plus standard care, not against another active treatment. It says nothing about how radium-223 compares with chemotherapy, newer hormonal agents, or PSMA-targeted radioligand therapy, and nothing about the best order to use them in.

A median survival difference of about three months is a real group effect and not a per-person promise. Some men in the trial lived far longer than the median and some far shorter.

Finally, the trial finished in 2013. Prostate cancer treatment has changed since, and where radium-223 belongs in a modern sequence is a question this evidence was never built to answer.

Sources

• FDA approval letter, NDA 203971 (Xofigo), 2013
• FDA label for Xofigo, 2013
• Drugs@FDA overview for NDA 203971
• Parker C et al., N Engl J Med 2013, ALSYMPCA (NCBI E-utilities)
• NCI: Radium-223 Improves Survival in Patients with Advanced Prostate Cancer
• NCI PDQ: Prostate Cancer Treatment (Health Professional Version)
• NCI SEER Stat Facts: Prostate Cancer

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

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