Lutetium-177 in metastatic prostate cancer: who is offered treatment earlier (PSMAddition)

Treatment with lutetium-177 can now be discussed at an earlier stage of metastatic prostate cancer, when the disease is still sensitive to hormone therapy. For a certain group of patients, this expands the options for initial treatment.

On July 31, 2026, the FDA approved a new indication for lutetium-177 (Pluvicto). In the US, it was authorized for use together with hormone therapy in PSMA-positive metastatic hormone-sensitive prostate cancer.

The approval was based on the phase III PSMAddition trial. Its results were published in The Lancet. Adding radioligand therapy improved disease control.

What happened

• The new indication concerns metastatic prostate cancer that remains sensitive to hormone treatment.
• Lutetium-177 was added to standard hormone therapy, which was continued in both groups.
• PSMA PET was used to select patients: the scan must confirm a suitable target in the tumor lesions.
• In PSMAddition, the treatment held back progression longer but was accompanied by a higher rate of adverse events.

Key trial numbers

PSMAddition enrolled 1,144 patients, 572 in each group. Lutetium-177-PSMA-617 together with androgen deprivation therapy and an androgen receptor pathway inhibitor was compared with the same hormone therapy without the radiopharmaceutical.

In the published analysis

• The relative risk of imaging-based progression or death was lower (HR 0.72; p=0.0021).
• Median radiographic progression-free survival had not yet been reached in either group.
• Grade 3 or higher adverse events were more frequent with the addition of lutetium-177 (51% vs. 43%).
• Dry mouth was also more frequent (46% vs. 4%); all of these events were grade 1 or 2.

In a subsequent updated analysis, the benefit in disease control persisted (HR 0.67). There was a positive trend in overall survival, but no statistically convincing benefit yet (HR 0.80). These results come from a later analysis and are presented separately.

Why this matters for practice

What does offering it earlier mean?

Pluvicto's previously approved indications concerned metastatic castration-resistant prostate cancer, when the disease progresses despite testosterone suppression. Back in 2025, the FDA had already allowed its use in some of these patients before taxane chemotherapy.

PSMAddition looks at the next step: using radioligand therapy before this resistance develops, at the stage of hormone-sensitive metastatic disease.

The trial enrolled patients who had not yet received treatment for this stage or had received it only for a short time.

Why is PSMA needed?

PSMA, or prostate-specific membrane antigen, is a protein on the surface of cells. The radiopharmaceutical binds to this target and delivers radioactive lutetium-177 to the cells. Its radiation damages tumor cells. This approach is called radioligand therapy.

PSMA and PSA are not the same thing. A PSA blood test helps monitor the disease, but it does not replace PSMA PET-CT when selecting patients for radioligand treatment.

In practice, this strengthens the role of imaging before a regimen is chosen. The doctor needs to assess the target in the tumor, the extent of the disease, kidney function and blood counts, and to determine the place of this method among other treatment options.

Limitations

The new indication applies to PSMA-positive metastatic hormone-sensitive prostate cancer. In the trial, lutetium-177 was added to hormone therapy. The results do not justify stopping hormone therapy and do not prove superiority over all other ways of intensifying initial treatment.

Targeted delivery of radiation does not rule out side effects. Possible effects include decreased blood counts, impaired kidney function, dry mouth, nausea and fatigue. Treatment requires monitoring of blood tests and compliance with radiation safety rules.

Lutetium-177-PSMA therapy is already being carried out in some specialized centers in Russia.

When a second opinion is especially useful

• Metastases were found recently, and the initial treatment regimen has to be chosen.
• Lutetium-177 therapy is being proposed, but it is unclear what data the indication is based on.
• PSMA PET-CT has not yet been performed, or its results need further review.
• Doctors disagree about the sequence of hormone therapy, chemotherapy and radioligand therapy.
• There is kidney disease, anemia or other circumstances that may affect treatment tolerability.

What to prepare for the consultation

• Histology report with the Gleason score.
• Discharge summaries on surgery, radiation and drug therapy, with treatment dates.
• CT, MRI and bone scan results.
• PSMA PET-CT report and images, if the scan has already been performed.
• PSA trend and testosterone results.
• Complete blood count and blood chemistry, including creatinine.
• Results of molecular testing and biomarker studies, if available.
• A list of comorbidities and current medications.

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