Radium-223 (Xofigo) in India — alpha therapy for bone-metastatic prostate cancer.

What is Radium-223?

Radium-223 was approved by the US FDA in May 2013 on the strength of the phase 3 ALSYMPCA trial of 921 patients, which demonstrated a 30 percent reduction in the risk of death versus best standard of care.¹ It remains the only alpha-emitting bone-targeted therapy in routine clinical use, and the only radioligand therapy specifically approved for the bone-metastatic prostate cancer phenotype it addresses.

At Theranostic Physicians, Radium-223 is administered as an outpatient slow intravenous injection in our day-care suite at FMRI Sector 44, Gurugram. The injection itself takes about a minute; the visit takes a few hours including pre-treatment blood checks. Most patients are home the same afternoon.

How Radium-223 works.

The mechanism is elegantly different from PSMA-targeted therapy. Radium-223 does not bind to a receptor on the cancer cell. It exploits a much older biology — the fact that chemically, radium behaves like calcium. Where the body lays down calcium, it lays down radium-223 too.³ The therapy works in three steps:

• Targeting. Bone metastases from prostate cancer are intensely osteoblastic — they drive aggressive new bone formation in and around the tumour deposit. When Radium-223 is injected intravenously, it is taken up at these sites of active bone turnover, exactly where the cancer is.³
• Delivery. Once incorporated into the bone matrix adjacent to the tumour, Radium-223 decays through a chain of short-lived daughter nuclides, releasing four alpha particles in the process.¹ Alpha particles are heavy and high-energy — carrying about 95 percent of the decay energy — with a tissue range of less than 100 micrometers, or roughly 2 to 10 cell diameters.
• Cytotoxicity. That short range is the whole point. Alpha radiation causes complex, irreparable double-strand DNA breaks in the immediately adjacent tumour cells, while the bone marrow just millimetres away is largely spared.¹ This is the reason Radium-223 has a substantially better marrow safety profile than the older beta-emitting bone-seekers (Sr-89, Sm-153).

The physical half-life is 11.4 days, long enough to be useful biologically but short enough that radioactivity has decayed away by the time the patient is between cycles. The main route of excretion is the gut — faeces, not urine — which is why most of the patient-counselling discussion about radiation safety is about bathroom hygiene rather than crowd avoidance.³⁵

Who is a candidate?

The FDA-approved indication is deliberately narrow — and that narrowness is part of what makes Radium-223 work. The three eligibility pillars:³

• Castration-resistant prostate cancer (CRPC). Disease progression on or after medical or surgical castration. Castrate-level testosterone (<50 ng/dL) should be confirmed and maintained throughout treatment.
• Symptomatic bone metastases. Multiple bone metastases on imaging, with bone pain or other skeletal symptoms. Asymptomatic patients were not the ALSYMPCA population — the label specifies symptomatic.
• No known visceral metastatic disease. No liver, lung, or other organ metastases. Lymph nodes are allowed (in ALSYMPCA, nodes up to 3 cm in short axis were permitted).

Beyond those three, we also assess:

• Bone marrow reserves. Absolute neutrophil count ≥ 1.5 × 10⁹/L, platelets ≥ 100 × 10⁹/L, haemoglobin ≥ 10.0 g/dL before the first dose; thresholds before subsequent doses are slightly lower per FDA label.³ Heavy prior chemotherapy (especially docetaxel and cabazitaxel) lowers reserves and raises caution.
• Prior treatment history. Whether the patient has had docetaxel, abiraterone, enzalutamide, and what the response patterns were. Active concurrent abiraterone is a contraindication — see the warning in the side-effects section.
• Imaging. Current PSMA-PET-CT and contrast-enhanced CT (or bone scan + CT) to confirm bone-predominant disease and exclude visceral spread within the last 6–8 weeks.
• Bone-health status. Use of bone-supportive agents (denosumab or zoledronic acid) is considered for patients at fracture risk — particularly relevant given the ERA-223 findings on fracture risk in combination with abiraterone.⁴

The six-injection protocol.

The FDA-approved Xofigo regimen is fixed — six injections of 55 kBq (1.49 microcurie) per kg of body weight, given at four-week intervals, as a slow intravenous push over about one minute. Safety and efficacy beyond six injections have not been studied.³ The course runs about 20 weeks from first to last dose.

Total treatment duration: approximately 20 weeks. The Dutch real-world registry reported a median treatment duration of 20 weeks with patients receiving a median of 5 cycles — some patients complete all 6, others stop earlier for tolerability, progression on imaging, or completed clinical benefit.⁸

ALSYMPCA and real-world outcomes.

The pivotal evidence for Radium-223 is the phase 3 ALSYMPCA trial — ALpharadin in SYMptomatic Prostate CAncer. 921 men with castration-resistant prostate cancer and symptomatic bone metastases were randomised 2:1 to six injections of Radium-223 or matching placebo, alongside best standard of care. The trial was terminated early at the prespecified interim analysis because the survival benefit had already been reached.¹

The headline numbers

The updated analysis of all 921 patients published in the New England Journal of Medicine reported a hazard ratio of 0.70 (95% CI 0.58–0.83, P<0.001) for death, with median overall survival of 14.9 months on Radium-223 versus 11.3 months on placebo.¹

Symptomatic skeletal events

The key secondary endpoint — time to the first symptomatic skeletal event (SSE) — was also significantly improved. The SSE composite included external-beam radiation for bone pain, symptomatic pathologic fracture, spinal cord compression, and tumour-related orthopaedic surgery: the kinds of events that fundamentally alter quality of life. Radium-223 delayed the median time to first SSE from 9.8 to 15.6 months (HR 0.66, 95% CI 0.52–0.83, P=0.00037).²

Real-world Dutch registry

The strongest confirmation outside the trial came from a prospective Dutch registry of 305 patients (300 evaluable) across 20 hospitals.⁸ In a heavily pre-treated population — 74 percent prior docetaxel, 80 percent prior abiraterone or enzalutamide — the median overall survival was 15.2 months, the 6-month symptomatic-skeletal-event-free survival was 83 percent, and the toxicity profile closely matched ALSYMPCA. The benefit holds up in real-world conditions.

Where it fits

The benefit of Radium-223 has been demonstrated in both docetaxel-pre-treated and docetaxel-naïve patients in ALSYMPCA — with comparable hazard ratios in subgroup analysis. Radium-223 is therefore deployed both before and after chemotherapy depending on the patient's situation and treatment history. The key constraint is not chemotherapy sequencing — it is the bone-predominant disease phenotype.

Cost of Radium-223 in India.

Radium-223 pricing is patient-weight dependent — the dose is calculated as 55 kBq per kg of body weight per injection — so we publish indicative ranges below and issue a written quote based on actual weight. The figures cover the therapy itself; diagnostic imaging, blood work, and any inpatient charges are billed separately by FMRI.

For context: the cost of a full six-cycle Radium-223 course in India is substantially lower than in the United States, the United Kingdom or Western Europe, while being delivered to the same FDA-approved standard. Many international patients travel to Gurugram specifically for this reason.

What about side effects?

Radium-223 has a more favourable side-effect profile than most systemic prostate cancer therapies — meaningfully better than docetaxel chemotherapy on tolerability. The alpha-particle range of less than 100 micrometers means the bone marrow next to the metastasis is largely spared, and the drug is not metabolised by liver or kidney. Most side effects are gastrointestinal and mild.³⁹

Common (≥ 10% of patients, ALSYMPCA)

• Nausea — 36% (vs 35% on placebo). Almost always mild, manageable with standard antiemetics.
• Diarrhoea — 25% (vs 15% on placebo). Usually mild; oral rehydration sufficient.
• Vomiting — 19% (vs 14% on placebo). Rare to require intervention.
• Peripheral oedema (swelling of legs/ankles/feet) — 13% (vs 10% on placebo).

Common laboratory findings

• Anaemia, lymphocytopenia, leukopenia, thrombocytopenia, neutropenia — the laboratory abnormalities most commonly observed. The majority are grade 1–2 (mild). Grade 3–4 events are uncommon in untreated patients but more frequent in those with prior docetaxel or cabazitaxel exposure.³
• Pain flare. A transient worsening of bone pain in the first few days after an injection is well-described in nuclear bone therapies. It is usually managed with standard analgesia and often precedes clinical response — though not a guarantee of one.¹⁰

Rare but clinically important

• Bone marrow failure / persistent pancytopaenia — reported in 2% on Xofigo vs 0% on placebo in ALSYMPCA. The most clinically significant toxicity; the reason blood counts are mandatory before every dose.³
• Dehydration — consequence of the GI side effects. Monitor oral intake; treat early.

Radiation safety at home

Patients and families often expect to be isolated after radioligand therapy. For Radium-223, this is not required. The SNMMI states explicitly that isolation from family or caregivers is not necessary after Radium-223 — the radiation is internal, alpha particles do not penetrate skin, and the patient is not a meaningful radiation source to others.⁵¹¹

General hygiene precautions are recommended for about 1 week after each injection, because the major route of elimination is via faeces:⁵¹¹

• Drink plenty of fluids and use the bathroom often, especially in the first 48 hours.
• Sit on the toilet when urinating (to reduce splashing). Flush at least twice after each use.
• Wash hands thoroughly with soap and water afterwards.
• Clean any spills of urine or faeces promptly; if they soil clothing, wash separately and promptly.
• Caregivers handling bodily fluids should use gloves.
• No restriction on hugging family, holding children, sleeping in the same bed, or going to work.
• Use condoms during treatment and for 6 months after the last injection — a precaution for the embryo-fetal radiation risk specified in the FDA label.³

When Lu-PSMA fits better.

Radium-223 and Lu-177 PSMA-617 (Pluvicto) are both radioligand therapies for advanced prostate cancer, but they are answering different clinical questions — and choosing between them is one of the more nuanced decisions in this space. They can also be sequenced; this is not always an either/or.

Choose Radium-223 when:

• Disease is bone-predominant with symptoms (bone pain, alkaline phosphatase elevation, multiple bone metastases on bone scan).
• There is no visceral metastatic disease on contrast CT.
• Bone marrow reserves are intact — particularly in patients who have not yet received docetaxel.
• PSMA-PET shows bone-restricted disease without significant nodal or visceral uptake.

Choose Lu-177 PSMA (or Ac-225 PSMA) when:

• Disease is multi-site — bone plus visceral metastases (liver, lung, lymph nodes >3 cm).
• PSMA-PET shows uniform, high-intensity uptake across all sites of disease.
• The patient has already had Radium-223 and now has progressing visceral or nodal disease.
• Soft-tissue disease is what is driving symptoms.

A common sequence in our practice: for an mCRPC patient with bone-dominant symptomatic disease and no visceral spread, Radium-223 first — six cycles, treating the bone microenvironment with the alpha range. Re-stage. If progression then declares in soft tissue or new nodes, transition to Lu-PSMA. If progression is still bone-predominant but with marginal counts, consider Ac-225 PSMA or further Lu-PSMA. The sequence is built around the disease, not the patient's preference for one isotope over another.

Next available Radium-223 slots.

Radium-223 cycles at our centre are scheduled by appointment. Each cycle is an outpatient day — reach the centre by 9 a.m., discharged by mid-afternoon. International patients typically combine the cycle with a single overnight stay in Gurugram. Isotope must be ordered 7 days in advance so reservations close one week before each listed slot.