If you have prostate cancer and have been told your cancer is PSMA-positive, you may have heard about PSMA radioligand therapy as a treatment option. Researchers are now exploring whether you could receive this treatment earlier in your care journey, rather than only after several other treatments have been tried.
If you have metastatic, PSMA-positive prostate cancer, this may become another treatment option for you in the future. Whether you could receive it depends on factors such as your cancer stage, PSMA scan results, previous treatments and the treatment pathways available where you live. In the UK, availability may differ from US approvals, so you should discuss your individual options with your specialist.
What Is PSMA?
If you have been told that your prostate cancer is PSMA-positive, it means your cancer cells carry higher levels of a protein called PSMA. If your cancer cells carry higher levels of PSMA, your doctors can use this target to find areas of cancer on PSMA PET scans and assess whether PSMA radioligand therapy could be suitable for you.
If your doctor finds that your prostate cancer has higher PSMA levels, this information can help guide your treatment options. PSMA allows your medical team to identify cancer on scans and, in suitable cases, deliver radiation directly to cancer cells.
What Is PSMA Radioligand Therapy?
PSMA radioligand therapy uses a PSMA-targeting molecule to carry radioactive treatment to your prostate cancer cells. Once it reaches cells with enough PSMA, lutetium-177 releases radiation that damages the cancer.
The advantage for you is that the treatment travels through your bloodstream, allowing it to reach prostate cancer that has spread to places such as your bones and lymph nodes.
Why Is Lutetium-177 Used?
When you receive lutetium-177 PSMA therapy, the radioactive element travels to prostate cancer cells that contain enough PSMA. This allows your treatment team to target cancer while limiting radiation exposure to surrounding healthy tissues. It also allows doctors to see how the treatment is distributed in your body.
Currently, lutetium-177 has the strongest clinical evidence among PSMA-targeted treatments, so if your specialist discusses PSMA radioligand therapy with you, this is the isotope you are most likely to hear about. Other isotopes such as actinium-225 are also being studied.
What Does Theranostics Mean?
Theranostics combines diagnosis and treatment using the same biological target. In prostate cancer, your PSMA PET scan can show whether your cancer has enough PSMA for targeted radioligand therapy.
This means your treatment can be matched more closely to the biology of your cancer rather than only where your cancer is located. Your PSMA PET scan helps your specialist decide whether this approach is likely to be suitable for you. However, your doctor will also consider that not every cancer cell in your body may express PSMA at the same level.
Where Was Lutetium-177 PSMA Originally Used?
If you have advanced prostate cancer that has stopped responding to hormone treatment, you may already be familiar with lutetium-177 PSMA as a later treatment option. Researchers are now asking whether using it earlier could help selected patients. The VISION trial showed that, for selected patients, adding this treatment could slow the cancer and help them live longer.
This raised an important question: if PSMA therapy can help when cancer is advanced, could using it earlier improve disease control for selected patients?
Why Might Giving Radioligand Therapy Earlier Help?
Using PSMA radioligand therapy earlier could potentially allow your cancer to be targeted before it becomes more resistant to treatment. Researchers are studying whether treating your cancer earlier could improve disease control and delay progression for selected patients.
- Earlier in your treatment journey: Researchers are studying whether using PSMA therapy sooner could target your cancer before treatment-resistant or PSMA-low tumour cells become more common.
- Better Treatment Fitness: You may be fitter and have better bone-marrow reserve before receiving several other treatments.
- Combined Treatment: PSMA therapy can be used alongside hormone treatment to attack your cancer in different ways.
- Earlier Cancer Control: If you have PSMA-positive cancer, treating it sooner may help delay progression in selected situations, although researchers are still studying the long-term benefits.
If you receive PSMA radioligand therapy earlier, you may also be exposed to additional radiation and side effects. Your specialist will need to weigh whether the possible benefits for you outweigh these risks.
How Far Has Lutetium-177 PSMA Moved Earlier?
| Study | Disease Setting | What Was Tested | What It Showed |
| VISION | Previously treated PSMA-positive mCRPC | Lu-PSMA + standard care | Improved progression-free and overall survival |
| PSMAfore | Taxane-naïve PSMA-positive mCRPC after ARPI progression | Lu-PSMA vs switching ARPI | Longer radiographic progression-free survival |
| PSMAddition | PSMA-positive metastatic hormone-sensitive disease | ADT + ARPI + Lu-PSMA vs ADT + ARPI | 28% relative reduction in radiographic progression or death |
| UpFrontPSMA | Newly diagnosed high-volume mHSPC | Lu-PSMA followed by docetaxel vs docetaxel | Higher rate of undetectable PSA at 48 weeks |
| LuTectomy | High-risk localised/locally advanced disease before surgery | Lu-PSMA before prostatectomy | Feasibility and early biological activity shown; long-term benefit unproven |
How Did PSMAfore Move Treatment Earlier in Castration-Resistant Disease?
If you have PSMA-positive metastatic castration-resistant prostate cancer and have not received chemotherapy, PSMAfore showed that lutetium-177 PSMA may offer longer control of disease compared with switching hormone-based treatments.
This was an important step towards understanding whether radioligand therapy could move earlier in the treatment pathway. The study helped establish that selected patients with PSMA-positive mCRPC can benefit from lutetium-177 PSMA before taxane chemotherapy.
What Was the PSMAddition Trial?
PSMAddition looked at whether you could receive lutetium-177 PSMA earlier, while your metastatic prostate cancer was still sensitive to hormone treatment. If you have metastatic prostate cancer that is still sensitive to hormone treatment, PSMAddition explored whether adding lutetium-177 PSMA to standard treatment could provide extra benefit.
The trial was important because it explored whether adding radioligand therapy earlier in your treatment journey could improve cancer control. It included men with PSMA-positive metastatic disease, including those diagnosed with metastatic cancer from the start or after previous treatment.
What Did PSMAddition Find?
PSMAddition found that adding lutetium-177 PSMA to your hormone treatment reduced the relative risk of radiographic progression or death by 28%. This was compared with ADT plus an ARPI without lutetium-177 PSMA.
If you are being treated for metastatic hormone-sensitive prostate cancer, these findings suggest that adding radioligand therapy may help control your cancer for longer. However, your doctor will also consider possible side effects and the current availability of this treatment.
Evidence Note
PSMAddition randomised 1,144 patients with PSMA-positive metastatic hormone-sensitive prostate cancer to androgen-deprivation therapy plus an androgen-receptor pathway inhibitor, either with or without lutetium-177 PSMA.
The addition of lutetium-177 PSMA reduced the relative risk of radiographic progression or death by 28% (HR 0.72). Overall-survival data were still immature at the published analysis. Grade 3 or worse adverse events occurred in 51% of patients receiving lutetium-177 PSMA compared with 43% in the control group, while dry mouth occurred in 46% versus 4% and was grade 1 or 2 in all reported cases.
What Did the July 2026 FDA Approval Change?
This represents a major development in combining lutetium-177 PSMA with an androgen-receptor pathway inhibitor for adults with PSMA-positive metastatic androgen pathway modulation-naïve or -sensitive prostate cancer.
This represents a major change in the potential treatment pathway, moving research interest towards using PSMA radioligand therapy earlier rather than only after multiple previous treatments. Even with this approval, you would still need suitable PSMA expression on imaging and other clinical factors before your specialist could consider this treatment for you.
Does the FDA Approval Mean the Treatment Is Standard in the UK?
No. If you are in the UK, a US FDA approval does not automatically mean you can receive the treatment through the NHS.
In the UK, NICE is still assessing lutetium-177 PSMA for hormone-sensitive metastatic prostate cancer. So, if you are in the UK, you should not assume this treatment is already routinely available through the NHS. Your specialist can explain what options are currently available through your local treatment pathway.
Research Insight
The phase 2 UpFrontPSMA trial tested another early-treatment strategy in 130 men with newly diagnosed, high-volume, PSMA-avid metastatic hormone-sensitive prostate cancer. Patients received either lutetium-177 PSMA followed by docetaxel or docetaxel alone.
At 48 weeks, 41% of evaluable patients in the lutetium-177 PSMA strategy had an undetectable PSA compared with 16% after docetaxel alone. The result supports further investigation of radioligand therapy earlier in the metastatic pathway, but the trial was relatively small and was not designed to establish this sequence as routine standard care.
Why Is PSMA PET Needed Before Treatment?
Before you have PSMA radioligand therapy, your doctor needs to check whether your cancer has enough PSMA to target. A PSMA PET scan can show which areas of your cancer are expressing the target and whether the treatment is likely to reach them.
PSMA PET is not only used to locate cancer; it also helps determine whether PSMA radioligand therapy is likely to be suitable. If your cancer does not express enough PSMA, radioligand treatment may not work effectively.
Does Every Prostate Cancer Express Enough PSMA?
No. Many prostate cancers have strong PSMA expression, but your cancer may not express it equally in every area. This means one tumour may show strong uptake on your PSMA PET scan while another shows much less.
This matters because PSMA radioligand therapy works best when cancer cells express enough of the target. One rationale for studying earlier treatment is that it may be given before treatment-resistant or PSMA-low tumour populations become more prominent, but this hypothesis still requires further clinical validation.
Could Radioligand Therapy Be Combined With Hormone Treatment?
Yes. PSMAddition showed that lutetium-177 PSMA can be given alongside ADT and an androgen-receptor pathway inhibitor. This means your cancer can be targeted in different ways at the same time.
This combination may improve cancer control, but if you receive more than one treatment together, your specialist will also consider whether the possible benefits outweigh the additional side effects and treatment burden.
Could Lutetium-177 PSMA Be Used Before Docetaxel?
Yes, in research settings. UpFrontPSMA tested lutetium-177 PSMA followed by docetaxel rather than giving the two treatments concurrently. At 48 weeks, 41% of evaluable patients in the lutetium-177 PSMA strategy had an undetectable PSA compared with 16% with docetaxel alone.
These phase 2 results support further study of lutetium-177 PSMA earlier in the metastatic hormone-sensitive pathway, but they do not establish this sequence as routine standard care.
UK Guidance Note
The July 2026 FDA approval applies in the United States and does not automatically establish NHS availability in the UK. NICE is currently developing appraisal ID6589 for lutetium-177 vipivotide tetraxetan in combination treatment for PSMA-positive hormone-sensitive metastatic prostate cancer, and the expected publication date is currently listed as to be confirmed.
It is also important to distinguish this new appraisal from NICE TA930. In 2023, NICE did not recommend lutetium-177 vipivotide tetraxetan for the older PSMA-positive hormone-relapsed metastatic indication after taxane-based chemotherapy and an anti-androgen, or when taxanes were medically unsuitable. UK access therefore depends on the specific indication and current NICE commissioning position rather than US FDA approval alone.
Could PSMA Radioligand Therapy Be Used Before Prostate Surgery?
In the 20-patient LuTectomy study, 9 men (45%) achieved a PSA decline of more than 50% after pre-operative lutetium-177 PSMA.
If you have high-risk prostate cancer, you may hear about research exploring PSMA therapy before surgery. However, current evidence is limited and this approach should still be considered experimental. The studies are small, so this should currently be viewed as a research strategy rather than standard treatment.
What Side Effects Can Lutetium-177 PSMA Cause?
Lutetium-177 PSMA can affect some healthy tissues as well as your cancer cells. You may experience dry mouth, tiredness, nausea or changes in your blood counts, particularly if you have already had several treatments.
Your doctor will also monitor possible effects on your kidney function and bone marrow, particularly if you have already received several treatments. This is particularly important if PSMA therapy is moved earlier in the treatment pathway, where long-term risks need further study.
Could Earlier Treatment Create New Problems?
Yes. If you receive lutetium-177 PSMA earlier, you may face extra treatment, side effects and radiation exposure even when your existing hormone treatment is controlling your cancer. Researchers still need to understand how earlier radioligand therapy affects cumulative bone-marrow toxicity and the optimal sequencing of later treatments such as chemotherapy.
The important question for you and your specialist is not only whether PSMA therapy can be given earlier, but whether the potential benefits outweigh the additional treatment risks, side effects and uncertainty.
What Could Earlier PSMA Therapy Mean for You?
What PSMA therapy means for you depends on your cancer’s stage and biology. If you have localised cancer, surgery or radiotherapy remains the usual approach, while earlier PSMA treatment before surgery is still experimental.
If you have metastatic disease, whether lutetium-177 PSMA is available depends on your disease state, PSMA PET findings, previous treatments and local treatment pathway. In the UK, the hormone-sensitive metastatic indication remains under NICE appraisal, so the July 2026 US approval should not be interpreted as automatic NHS availability.
Myth vs Fact
| Myth | Fact |
| PSMA radioligand therapy is only used after chemotherapy. | PSMAfore demonstrated benefit before taxane chemotherapy in selected mCRPC, while PSMAddition led to a 2026 US indication in PSMA-positive metastatic hormone-sensitive disease. |
| PSMAddition proved that earlier PSMA therapy helps patients live longer. | PSMAddition improved radiographic progression-free survival, but overall-survival data were still immature at the published analysis. |
| FDA approval means the treatment is automatically available on the NHS. | No. If you are in the UK, your access depends on NICE appraisal, NHS commissioning and whether this treatment is available through your local pathway. The NICE hormone-sensitive appraisal remains in development. |
| Every prostate cancer expresses enough PSMA for treatment. | PSMA expression can vary between patients and between tumour deposits. PSMA PET imaging is required to determine suitability. |
| UpFrontPSMA proved lutetium-177 PSMA should routinely be given with chemotherapy. | UpFrontPSMA was a small phase 2 trial that tested lutetium-177 PSMA followed by docetaxel. It supports further study but does not establish routine standard care. |
| Lutetium-177 PSMA before prostate surgery is already an established treatment. | No. LuTectomy involved only 20 patients and primarily established feasibility and early safety. Long-term cancer-control benefit remains unproven. |
| Earlier treatment has no downside because the cancer has had less treatment. | Earlier radioligand therapy adds radiation exposure and can cause dry mouth, blood-count changes and other adverse effects. Long-term sequencing and cumulative toxicity still matter. |
Key Takeaways
- PSMA radioligand therapy uses a PSMA-targeting molecule to deliver radioactive lutetium-177 to suitable prostate cancer cells.
- PSMAfore showed that lutetium-177 PSMA can improve radiographic progression-free survival before taxane chemotherapy in selected PSMA-positive mCRPC.
- PSMAddition moved radioligand therapy into PSMA-positive metastatic hormone-sensitive disease and reduced the relative risk of radiographic progression or death by 28%.
- Overall-survival data from PSMAddition were still immature at the reported analysis, so the final long-term survival benefit remains uncertain.
- The FDA approved lutetium-177 PSMA with an ARPI for selected PSMA-positive metastatic hormone-sensitive disease on 31 July 2026, but this does not establish NHS availability.
- PSMA PET imaging remains essential because PSMA expression is heterogeneous and not every patient is suitable for treatment.
- UpFrontPSMA and LuTectomy support research into still-earlier treatment, but these approaches are not established routine UK care.
- Using radioligand therapy earlier means balancing better disease control against additional radiation, side effects and uncertainty about long-term treatment sequencing.
Frequently Asked Questions
1. What Is PSMA Radioligand Therapy?
PSMA radioligand therapy uses a PSMA-targeting molecule to deliver radioactive lutetium-177 directly to suitable prostate cancer cells. It can reach cancer that has spread to areas such as your bones and lymph nodes.
2. Could PSMA Radioligand Therapy Be Used Earlier?
PSMAddition showed a significant improvement in radiographic progression-free survival when lutetium-177 PSMA was added to ADT plus an ARPI in selected PSMA-positive metastatic hormone-sensitive disease.
3. Who Could Be Suitable for Lutetium-177 PSMA Therapy?
Your suitability depends on factors such as your cancer stage, previous treatments and whether your cancer shows enough PSMA on a PSMA PET scan. Your overall health and current treatment plan will also be considered.
4. Why Do You Need a PSMA PET Scan Before Treatment?
A PSMA PET scan helps your doctor see whether your cancer cells have enough PSMA for the treatment to target. It can also show where the cancer is located and whether radioligand therapy is likely to be suitable for you.
5. Does Every Prostate Cancer Express Enough PSMA?
No. Your prostate cancer may show different levels of PSMA expression in different areas. If some cancer cells have little or no PSMA, they may be less responsive to PSMA-targeted treatment.
6. What Did the PSMAddition Trial Find?
PSMAddition found that adding lutetium-177 PSMA to hormone treatment reduced the relative risk of radiographic progression or death by 28% compared with ADT plus an androgen-receptor pathway inhibitor without lutetium-177 PSMA. Longer follow-up is still needed, so your specialist may not yet be able to say how much this treatment improves long-term survival.
7. Can Lutetium-177 PSMA Be Combined With Hormone Treatment?
This approach allows doctors to target prostate cancer through different treatment mechanisms at the same time, although combining treatments can also increase side effects.
8. Could PSMA Therapy Be Used Before Prostate Surgery?
It is possible in research settings, but this approach remains experimental. Early studies have explored lutetium-177 PSMA before surgery, but there is not yet enough evidence for it to be considered standard treatment.
9. What Side Effects Can Lutetium-177 PSMA Cause?
You may experience side effects such as dry mouth, tiredness, nausea or changes in your blood counts. Your doctor will also monitor your kidneys and bone marrow, particularly if you have already received several treatments.
10. Is Earlier PSMA Therapy Available in the UK?
Not necessarily. Although the FDA has approved earlier use for selected men with PSMA-positive metastatic prostate cancer, US approval does not automatically make the treatment routinely available through the NHS. UK availability depends on NICE guidance and local treatment pathways.
Final Thoughts: What Earlier PSMA Therapy Could Mean for Your Prostate Cancer Treatment
Earlier PSMA radioligand therapy could give some men with advanced prostate cancer another way to control their disease, but its suitability depends on your cancer stage, PSMA expression, previous treatments and overall health. If you are considering this approach, your specialist can help you understand whether the potential benefits outweigh the risks and whether it is available through your treatment pathway.
If you are experiencing urinary symptoms or changes in PSA, you can contact our team at Prostate Clinic London to arrange a consultation and discuss your concerns with a specialist.
References:
- National Institute for Health and Care Excellence (NICE) (2026) Lutetium-177 vipivotide tetraxetan in combination for treating PSMA-positive hormone-sensitive metastatic prostate cancer [ID6589]. Technology appraisal in development, GID-TA11766. Available at: https://www.nice.org.uk/guidance/indevelopment/gid-ta11766
- U.S. Food and Drug Administration (FDA) (2026) FDA approves lutetium Lu 177 vipivotide tetraxetan with androgen receptor pathway inhibitor therapy for metastatic androgen pathway modulation-naïve or -sensitive prostate cancer. 31 July 2026. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lutetium-lu-177-vipivotide-tetraxetan-androgen-receptor-pathway-inhibitor-therapy
- Tagawa, S.T., Sartor, O., Piulats, J.M., Saad, F., Fizazi, K., Reid, A. et al. (2026) ‘[177Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial’, The Lancet, 408(10557), pp. 793–807. Available at: https://pubmed.ncbi.nlm.nih.gov/42561994/
- Morris, M.J., Castellano, D., Herrmann, K., de Bono, J.S., Shore, N.D., Chi, K.N. et al. (2024) ‘177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial’, The Lancet, 404(10459), pp. 1227–1239. Available at: https://pubmed.ncbi.nlm.nih.gov/39293462/
- Sartor, O., de Bono, J., Chi, K.N., Fizazi, K., Herrmann, K., Rahbar, K. et al. (2021) ‘Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer’, The New England Journal of Medicine, 385(12), pp. 1091–1103. Available at: https://pubmed.ncbi.nlm.nih.gov/34161051/
- Azad, A.A., Bressel, M., Tan, H., Voskoboynik, M., Suder, A., Weickhardt, A.J. et al. (2024) ‘Sequential [177Lu]Lu-PSMA-617 and docetaxel versus docetaxel in patients with metastatic hormone-sensitive prostate cancer (UpFrontPSMA): a multicentre, open-label, randomised, phase 2 study’, The Lancet Oncology, 25(10), pp. 1267–1276. Available at: https://pubmed.ncbi.nlm.nih.gov/39293461/
- Eapen, R.S., Buteau, J.P., Jackson, P., Mitchell, C., Oon, S.F., Alghazo, O. et al. (2024) ‘Administering [177Lu]Lu-PSMA-617 prior to radical prostatectomy in men with high-risk localised prostate cancer (LuTectomy): a single-centre, single-arm, phase 1/2 study’, European Urology, 85(3), pp. 217–226. Available at: https://pubmed.ncbi.nlm.nih.gov/37891072/