This article covers bone-targeted treatment for metastatic castration-resistant prostate cancer (mCRPC). It's for men whose cancer has spread to bone and hormone therapy is no longer working. If your oncologist mentioned two bone-targeted radioactive treatments - lutetium Lu-177 vipivotide tetraxetan (Lu-177 PSMA, brand name Pluvicto) and radium-223 dichloride (brand name Xofigo) - this guide explains what makes them different, who might benefit from each one, and what to ask before you start treatment.
What Each Therapy Does
Lu-177 PSMA: a molecule that finds cancer cells
Lu-177 PSMA is a radioligand therapy. It pairs a targeting molecule with radioactive lutetium-177. The molecule attaches to PSMA (prostate-specific membrane antigen), a protein on prostate cancer cells. Once it binds to a cell with PSMA, lutetium-177 releases beta radiation that destroys that cell and nearby ones. Prostate cancer cells can express PSMA anywhere in the body: bone, lymph nodes, soft tissue, and organs. This means Lu-177 PSMA can potentially reach cancer in all these places. Our guide on how Lu-177 PSMA targets prostate cancer cells explains the mechanism in more detail.
Before you can receive Lu-177 PSMA, you need a PSMA-PET scan using a gallium-68 PSMA-11 tracer to confirm your lesions express enough PSMA. If the scan shows absent or very low uptake, Lu-177 PSMA may not work well for you, and your team will consider other options.
Radium-223: radiation that travels to bone like calcium
Radium-223 works on a completely different basis. Radium is chemically similar to calcium. The body naturally sends it to areas of high bone turnover. That's exactly where bone metastases grow. Once there, it emits alpha particles with a very short range, less than 100 micrometers. The radiation damage stays close to the bone lesion and mostly spares healthy tissue.
Radium-223 works for men with symptomatic bone metastases and no cancer in organs like the liver, lungs, or intestines. The FDA approved it in May 2013 based on the ALSYMPCA phase 3 trial. Unlike Lu-177 PSMA, which targets a protein, radium-223 reaches bone through chemical affinity. No PSMA-PET scan is needed. However, radium-223 cannot reach soft tissue, lymph nodes with disease, or organs. This is both its main strength and its main limit. You can learn more from the National Cancer Institute.
How Do Lu-177 PSMA and Radium-223 Compare for Bone Metastases in mCRPC?
| Factor | Lu-177 PSMA (Pluvicto) | Radium-223 (Xofigo) |
|---|---|---|
| Sites it can target | Bone, lymph nodes, soft tissue, and visceral metastases - wherever PSMA is expressed | Bone metastases only; does not reach soft tissue or organs |
| Eligibility scan required | Yes - PSMA-PET scan required to confirm PSMA expression before starting | No PSMA-PET scan needed; bone scan and clinical review are used |
| Visceral metastases allowed? | Yes - not restricted to bone-only disease | No - visceral metastases exclude patients from treatment |
| Treatment sessions | Up to 6 infusions, about 6 weeks apart (about 36 weeks total) | 6 injections, one every 4 weeks (about 24 weeks total) |
| Phase 3 trial: median overall survival | 15.3 months vs 11.3 months with standard care alone (VISION trial) | 14.9 months vs 11.3 months with placebo plus standard care (ALSYMPCA trial) |
| Most common side effects | Dry mouth, fatigue, nausea, kidney stress, low blood counts | Nausea, diarrhea, vomiting, mild bone marrow suppression; fracture risk if combined with abiraterone |
Sources: VISION trial - PMC (2021); ALSYMPCA trial - National Cancer Institute.
The survival numbers from each trial look similar on the surface. But each trial enrolled different patients and used different comparison arms, so a direct numerical comparison is not reliable. What the table shows is that these therapies suit different disease patterns. If your cancer has spread beyond bone, only Lu-177 PSMA can potentially reach those non-bone sites. If your disease is only in bone and symptomatic, both may be options. Factors like PSMA expression level, kidney function, and prior treatment history will guide the final choice.
The First Question: Is Your Cancer Confined to Bone?
This is the single most important factor in choosing between these two treatments. Radium-223 is approved specifically for patients whose cancer has spread to bone with no involvement of organs such as the liver, lungs, or intestines. If your imaging shows any visceral lesions, radium-223 is generally not appropriate. Lu-177 PSMA has no such restriction. Patients in the VISION trial could have visceral disease and still be eligible, provided PSMA expression was confirmed on imaging. A 2025 study comparing cancer-control outcomes in mCRPC patients shows how the two treatments serve different populations within the bone-metastatic disease group.
For men with bone-only mCRPC and no soft-tissue spread, both treatments may be possible. Your team will then look at PSMA expression on PET imaging, your prior treatment history, performance status, and your kidney and bone marrow function to help narrow the choice.
Does Your Tumor Express Enough PSMA?
Lu-177 PSMA is not a universal option for all prostate cancer patients. Your tumor cells need to express the PSMA protein at a level high enough to show up on a PSMA-PET scan. In the VISION trial, eligibility required at least one measurable lesion with PSMA uptake greater than liver uptake on PET imaging, with no measurable lesion showing absent PSMA uptake. Men whose scans show faint or missing PSMA signal are unlikely to benefit and generally are not offered this therapy.
If your PSMA-PET scan shows low or mixed results, your oncologist may consider radium-223 (if disease is bone-confined and symptomatic), external-beam radiotherapy to specific painful lesions, or a clinical trial. Our article on whether Lu-177 PSMA can help bone pain and what to consider when it is not an option covers this decision in more detail.
What the Evidence Shows
Both treatments have been tested in large, randomized phase 3 trials - the strongest level of clinical evidence in oncology outside of long-term survival follow-up.
The VISION trial showed that adding Lu-177 PSMA to standard care improved median overall survival to 15.3 months, compared with 11.3 months for standard care alone. This was in men who had already received both androgen receptor pathway inhibitors and at least one taxane chemotherapy course. The treatment also significantly extended the time before imaging showed disease progression.
The ALSYMPCA trial showed median overall survival of 14.9 months with radium-223 versus 11.3 months with placebo plus standard care, with a hazard ratio of 0.70. It also significantly delayed the time to a first symptomatic skeletal event - fractures or spinal cord compression - by about 5.8 months compared with placebo. That delay in bone complications matters deeply for day-to-day quality of life.
Some emerging research involves using both treatments at different points during the disease course rather than choosing just one. Studies show that receiving radium-223 before Lu-177 PSMA does not appear to reduce the effectiveness of a subsequent Lu-177 PSMA course. This means the two treatments may not be mutually exclusive over the full arc of your care. The optimal sequence is still being studied, and you should discuss this with your oncologist before starting either treatment.
How the Side Effects Differ
Both treatments deliver radiation to cancer cells but through different methods. Their side-effect profiles differ in important ways.
Radium-223 mainly causes gastrointestinal effects. Nausea, diarrhea, and vomiting are the most common. Mild bone marrow suppression can occur because alpha particles reach some marrow cells near the lesions. In the ALSYMPCA trial, about 2% of patients on radium-223 had bone marrow failure. Fatigue is also common. One important safety note: combining radium-223 with abiraterone (an androgen receptor pathway inhibitor) was linked to a higher rate of bone fractures and higher mortality in a post-approval study. This combination is generally avoided now. Radium-223 does not affect salivary glands and does not cause dry mouth.
Lu-177 PSMA has a different profile. PSMA protein is also expressed in salivary glands and kidneys, so those organs receive some incidental radiation alongside the cancer cells. Research on the safety of Lu-177-based therapies identifies dry mouth as the most frequently reported side effect. It can be persistent. Fatigue, low blood counts, and mild nausea are also reported. Kidney function needs monitoring before and during treatment. Patients with pre-existing kidney problems may need dose adjustments.
Men on either treatment often receive long-term androgen deprivation therapy (ADT) at the same time. ADT can reduce bone density over time, which matters when bone metastases are already present. If you want over-the-counter support for bone health during this period, you might explore available options. Always check with your oncologist before adding any supplement, as some may affect bloodwork or interact with treatment.
Practical Differences in How Each Treatment Is Given
Radium-223 is given as a quick intravenous injection once every four weeks for six doses - about six months of treatment in total. Because no PSMA-PET scan is required first, treatment can sometimes start faster. Radium-223 clears primarily through the bowel, so patients are advised to flush twice and practice careful hand hygiene in the days after each dose.
Lu-177 PSMA is given as a slower intravenous infusion, typically once every six weeks for up to six cycles - about nine months of treatment. Because it clears partly through the kidneys, urine precautions are important in the 24-48 hours after each infusion. Regular blood tests and kidney function monitoring are built into the schedule between cycles. If you want to compare Lu-177 PSMA against a third bone-targeted approach, our article on Lu-177 PSMA versus external-beam radiotherapy for bone metastases in mCRPC walks through that decision.
Questions Worth Asking Before You Decide
- Have I had a PSMA-PET scan, and what did it show about PSMA expression across all my lesions?
- Does my imaging show any disease outside bone - in lymph nodes, the liver, or the lungs?
- What is my current kidney function and blood count, and does either change my options?
- Am I currently on abiraterone, and does that affect whether radium-223 is safe for me?
- What prior treatments have I had, and how does that history affect eligibility for each option?
- If I start one treatment now, can I still consider the other later if my disease progresses?
- Is there a clinical trial combining or sequencing these treatments that might suit my situation?
If you have not yet had a PSMA-PET scan, or if your oncologist has not raised either of these options, getting an independent nuclear-medicine review before starting can be valuable. You can have your scans reviewed by the Art of Healing Cancer team, nuclear-medicine specialists who can assess your PSMA expression and help you decide which treatment fits your disease pattern, including what options remain if neither works for you.
When to Talk to Your Doctor
Speak with your oncologist or a nuclear-medicine specialist if your prostate cancer has spread to bone and your current therapy is no longer holding the disease in check. Both Lu-177 PSMA and radium-223 are treatments that may be considered in mCRPC. Which one fits your case, if either, depends on where your metastases are, whether your tumor expresses PSMA on a PET scan, and how well your kidneys and bone marrow are functioning. If neither option has come up in your consultations, ask directly whether a theranostics or nuclear-medicine review is appropriate for your stage of disease.
This article is for general information and is not a substitute for medical advice. Always consult your oncologist or care team about your specific situation.
Frequently asked questions
Can I have both Lu-177 PSMA and radium-223 as part of my treatment plan?
Research suggests these two treatments may not be mutually exclusive. A 2025 study found that patients who received radium-223 before Lu-177 PSMA had similar cancer-control outcomes to those who had Lu-177 PSMA without prior radium-223. Whether sequential use makes sense in your case depends on how your disease responds and what your oncologist recommends. Discuss this possibility before committing to either treatment.
Do I need a PSMA-PET scan before I can start radium-223?
No. Radium-223 does not require a PSMA-PET scan. It reaches bone metastases through a chemical process similar to the way calcium behaves in the body, so eligibility is confirmed using a bone scan and clinical assessment of your symptoms. A PSMA-PET scan is required, however, to qualify for Lu-177 PSMA therapy.
My cancer has spread to my liver as well as my bones. Does that rule out radium-223?
Yes, in most cases. Radium-223 is approved specifically for patients with bone metastases and no visceral (organ) metastases. If imaging shows spread to the liver, lungs, or other organs, radium-223 is generally not appropriate. Lu-177 PSMA may still be an option even with visceral disease, as long as your tumors show adequate PSMA expression on a PSMA-PET scan.
Which treatment is more likely to cause nausea?
Nausea, vomiting, and diarrhea are the most commonly reported side effects with radium-223, because the drug clears largely through the bowel. With Lu-177 PSMA, dry mouth and fatigue are the most frequently reported effects; nausea can also occur but tends to be less prominent than with radium-223. Both treatments can be supported with anti-nausea medications prescribed by your care team.
My disease is bone-only. How do doctors choose between the two options in that situation?
Several factors guide this choice when disease is bone-only. Your oncologist will consider whether your tumors show adequate PSMA expression on a PSMA-PET scan, your kidney and bone marrow function, what prior treatments you have had - particularly whether you have already received androgen receptor pathway inhibitors and taxane chemotherapy - and whether you are currently on abiraterone. A nuclear-medicine specialist and your oncologist will typically review all of these factors together before recommending one option over the other.
Is it safe to combine radium-223 with abiraterone?
This combination is generally avoided. A post-approval study found that combining radium-223 with abiraterone was associated with higher rates of bone fractures and higher overall mortality compared with radium-223 alone. If you are currently on abiraterone and radium-223 is being considered, tell your oncologist before starting so the sequencing of your treatments can be planned carefully.