Advanced prostate cancer: study follows 333 men treated with lutetium-177

A prospective registry at seven centers in Switzerland followed 333 men with prostate cancer that had spread to other parts of the body and was progressing despite testosterone suppression. They received lutetium-177 bound to PSMA-I&T. Among the 308 patients whose PSA was assessed after the start of therapy, 137 had a drop of at least 50% in the marker, a rate of 44.5%.

Published in The Lancet Medical Imaging & Theranostics, the study had safety as its primary endpoint and PSA response as a secondary endpoint. The results describe the treatment as used in routine practice. Because there was no comparison group, it is not possible to determine whether the therapy extended life compared with standard care, or to estimate the size of any potential benefit.

What PSA shows

PSA is a protein measured in the blood to monitor prostate cancer. A substantial drop during treatment is a sign of activity against the disease, but it does not replace assessment of symptoms, imaging and the patient’s overall condition.

“On its own, it does not allow us to conclude that the patient will live longer or have a better quality of life,” explains urologist and general surgeon Romulo Nunes, commenting on the role of PSA.

Of the 333 men treated, five moved on to other studies after the first cycle and 20 died before the scheduled laboratory assessment. These patients were left out of the PSA response calculation. This exclusion needs to be taken into account when interpreting the 44.5% rate.

The researchers also reported a median overall survival of 13.2 months among the 333 patients. The median corresponds to the point at which the estimated survival reaches 50%. This analysis was exploratory, added after the study’s objectives were initially defined. The figure describes what was observed in this group; it does not measure the time of life added by the radiopharmaceutical.

How the therapy reaches the tumor

The therapy combines a molecule that recognizes PSMA, a protein present on the surface of many prostate cancer cells, with lutetium-177, a radioactive element. This combination makes it possible to deliver radiation to cells that express the target.

The disease stage evaluated in the registry is called metastatic castration-resistant prostate cancer. At this stage, the tumor progresses even with testosterone kept at low levels by treatment. Most participants had received other cancer treatments, although 86 of the 333 men, or 26%, had not undergone chemotherapy.

Selection included PSMA PET, an imaging test that shows whether the target is present in the lesions, and an assessment of clinical condition. Local teams interpreted the scans, with no central review of the images. Differences between centers make the sample and follow-up less uniform.

Safety concerns

The most relevant abnormalities involved blood cells. Grade 3 anemia occurred in 26 of the 295 patients with available data, or 8.8%. Grade 3 lymphopenia was recorded in 54 of 256, or 21.1%. This abnormality is a reduction in lymphocytes, a type of immune cell. Grade 3 indicates a severe abnormality on the scale used to classify adverse events. The totals assessed vary because some tests were not available at every center.

The authors consider the clinical relevance of the observed lymphopenia uncertain. Its frequency does not, by itself, demonstrate an increase in infections in this group. During the observation period, no treatment-emergent adverse events classified as grade 4 or 5 were recorded—categories that indicate life-threatening events or death, respectively.

In the kidney assessment, there were grade 1 or 2 creatinine increases in 47 of 295 patients, with no grade 3 or higher kidney toxicity. The median follow-up of 12 months, however, limits conclusions about late harms, including those that may emerge after radiation exposure.

Nunes notes that the clinical assessment takes into account the bone marrow, the kidneys, the patient’s ability to carry out activities and prior therapies. The urologist also draws attention to urinary obstructions that could compromise kidney function. These are the specialist’s considerations about clinical practice; the registry did not present a specific analysis of urinary obstruction.

According to the specialist, the choice of treatment involves urology, medical oncology, nuclear medicine and radiation oncology. The team discusses the expected benefit, adverse effects, logistics and the patient’s preferences.

Pain and quality of life

The pain and quality-of-life results came from questionnaires administered at two centers. Among 164 patients with available data, pain improved in 24 and worsened in 23. For quality of life, there was improvement in 15 and worsening in 18. These numbers do not indicate widespread improvement, nor do they allow the changes to be attributed to the therapy, since there was no comparison with another group.

The assessment adds the patients’ perspective but covers only some of the 333 men treated.

PSMA I&T and PSMA 617

The PSMA-I&T used in the Swiss registry is different from PSMA-617, the ligand in Pluvicto, which is registered in Brazil. A ligand is the molecule that recognizes the target and carries the radioactive component. The two products have the same target and use lutetium-177, but their chemical structures are not identical and may influence how the drug is distributed and eliminated.

Nunes emphasizes that the products cannot automatically be considered interchangeable. Results for one ligand should not be transferred directly to the other. Thus, the Swiss registry adds information about PSMA-I&T without, by itself, changing the treatment’s indications in Brazil.

Comparative studies are needed to establish any advantages of PSMA-I&T over other options and to define the best sequence of use. The assessment must take into account survival, symptoms, quality of life and safety, in addition to the drop in PSA.

Sources for this report

Chirindel A et al. PSMA-targeted radioligand therapy with [177Lu]Lu-PSMA-I&T in metastatic castration-resistant prostate cancer: a prospective, multicentre, Swiss registry study. The Lancet Medical Imaging & Theranostics, 2026. DOI: https://doi.org/10.1016/j.lanmit.2026.100010. Article and supplementary appendix. Contribution from Romulo Nunes, urologist and general surgeon, submitted to the newsroom.