Lu-PSMA-617 reduces disease progression versus deferred ADT in oligometastatic HSPC in phase 2 trialCan a targeted radiation drug delay prostate cancer progression without hormone therapy?

The Lancet. Oncology Published April 6, 2026 Study authors: Privé Bastiaan M, Noordzij Walter, Muselaers Constantijn H J, de Jong Igle J, van Oort Inge M, Janss… PubMed ↗ NCT04443062 ↗ DOI ↗ Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

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Key Takeaway

Consider Lu-PSMA-617 data promising but preliminary; phase 3 confirmation is needed.

This phase 2 randomized controlled trial enrolled 58 eligible men with biochemically recurrent oligometastatic hormone-sensitive prostate cancer (HSPC) following radical prostatectomy or radiotherapy from academic and community hospitals in the Netherlands and Cyprus. Patients were randomized to receive Lu-PSMA-617 (two cycles of 7.4 GBq every 6 weeks, with potential for two additional cycles) or to standard of care with deferred androgen deprivation therapy (ADT) and active monitoring.

The primary outcome was disease progression. During the first 30 weeks, disease progression occurred in 2 of 29 (7%) patients in the Lu-PSMA-617 group versus 27 of 29 (93%) in the control group (p<0.0001). Median progression-free survival was 25 months (IQR 15 to not reached) for the intervention group versus 5 months (IQR 3-7) for the control group (HR 0.07, 95% CI 0.03-0.17; p<0.0001).

Regarding safety, in the Lu-PSMA-617 group, grade 3 adverse events included dry eyes in 1 (3%) patient and lymphocyte count decrease in 3 (10%) patients. Common low-grade events were dry mouth (66%), fatigue (55%), and nausea (48%). No serious adverse events were reported with Lu-PSMA-617. In the control group, grade 3-4 events included hypertension (17%), lymphocyte count decrease (3%), gallbladder infection (3%), and myocardial infarction (3%).

Key limitations include the small sample size (58 patients) and the phase 2 design, which precludes definitive conclusions. The study was funded by the Dutch Prostate Cancer Foundation and Novartis. While the results are promising, they should be interpreted cautiously, and clinical application should await validation from larger phase 3 trials.

When prostate cancer starts to return after surgery or radiation, the standard next step is often hormone therapy, which can come with difficult side effects. A new study asked if a different treatment—a targeted radiation drug called Lu-PSMA-617—could delay that step and keep the cancer in check longer. The trial involved 58 men whose cancer was beginning to spread to a few sites. The results were striking: within the first 30 weeks, cancer progressed in only 7% of men who received the drug, compared to 93% of men who were monitored as usual. On average, the drug extended the time before the cancer worsened from 5 months to 25 months. The treatment was generally well-tolerated, with most side effects like dry mouth and fatigue being mild. However, it's important to remember this is a phase 2 trial with a small number of patients. While the results are promising and show a clear signal, we need larger studies to confirm the benefit and understand the long-term effects before this could become a standard option.

What this means for you:

A targeted radiation drug significantly delayed prostate cancer progression in a small, early trial.

Study Details

Study typeRct

EvidenceLevel 2

Follow-up216.0 mo

PublishedApr 2026

PMID41926960

TrialNCT04443062

View Original Abstract ↓

BACKGROUND: [Lu]Lu-prostate-specific membrane antigen (PSMA)-617 (Lu-PSMA-617) is a novel treatment for metastatic castration-resistant prostate cancer. Here, we aimed to evaluate Lu-PSMA-617 in patients with PSMA-expressing oligometastatic hormone-sensitive prostate cancer (HSPC). METHODS: BULLSEYE was an open-label, randomised, phase 2 trial in three academic hospitals in the Netherlands (Radboud University Medical Center, University Medical Center Groningen, and University Medical Center Amsterdam) and one community hospital in Cyprus (German Oncology Center). Eligible participants were men, aged 18 years or older, with biochemically recurrent prostate cancer following radical prostatectomy or radiotherapy, Eastern Cooperative Oncology Group performance status score of 0-1, a PSA doubling time of less than 6 months and PSA amounts of over 1·0 μg/L. Paients aged 18 years or older with recurrent hormone sensitive prostate cancer following radical surgery or radiotherapy were randomly asigned (1:1) using a centralised web-based system with block randomisation to Lu-PSMA-617 (intervention) or standard of care (control) of deferred androgen deprivation therapy (ADT). The treatment group received two cycles of 7·4 GBq Lu-PSMA-617 every 6 weeks. 6 weeks after the second treatment cycle, patients with residual PSMA-expressing disease on PSMA-PET-CT, and no grade 3 or worse treatment-related adverse events received two additional cycles of 7·4 GBq Lu-PSMA-617 given 6 weeks apart.The control group did not receive treatment but underwent active monitoring for disease progression. Co-primary endpoints were the proportion of patients with disease progression, and time to disease progression with the same endpoint. Primary, secondary, and safety endpoints were assessed in the per-protocol population, who all received at least one 1 dose of 177Lu-PSMA-617. This trial is registered with ClinicalTrials.gov (NCT04443062) and has completed accrual. FINDINGS: Between April 20, 2020, and July 29, 2024, 78 males were screened and 58 were eligible (29 intervention and 29 control). 56 patients were white, one was Asian, and one was African. Patients in the intervention group received a median of four cycles (IQR 4-4) of Lu-PSMA-617. At data cutoff (March 31, 2025), median follow-up time was 27 months (IQR 18-32). During the first 30 weeks, disease progression was reported in two (7%) of 29 patients in the intervention group versus 27 (93%) of 29 patients in the control group (p<0·0001). Median progression-free survival (per-protocol) was 25 months (IQR 15 to not reached) for intervention group versus 5 months (IQR 3-7) for control (hazard ratio [HR] 0·07, 95% CI 0·03-0·17; p<0·0001). One (3%) patient in the intervention group developed grade 3 dry eyes, which resolved with supportive treatment, and grade 3 lymphocyte count decrease was observed in three (10%) patients in the treatment group. The control group had five (17%) patients with grade 3 hypertension, one (3%) patient with a grade 3 decrease in lymphocyte count, one (3%) patient with a grade 4 gallbladder infection, and one (3%) patient with a grade 4 myocardial infarction. There were no treatment-related grade 4 adverse events or deaths. No serious adverse events were reported in patients who received Lu-PSMA-617. The most common adverse events were grade 1 dry mouth in 19 (66%) patients in the treatment group versus three (10%) patients in the control group, fatigue in 16 (55%) patients in the treatment group versus six (21%) patients in the control group, and nausea in 14 (48%) patients in the treatment group versus three (10%) patients in the control group. No deaths were attributed to the treatment in either group. INTERPRETATION: Lu-PSMA-617 showed promising response rates and delayed disease progression in patients with oligometastatic HSPC in this trial. In addition, most treatment-related adverse events were low grade. FUNDING: Dutch Prostate Cancer Foundation (Prostaatkankerstichting) and Novartis.

Lu-PSMA-617 reduces disease progression versus deferred ADT in oligometastatic HSPC in phase 2 trialCan a targeted radiation drug delay prostate cancer progression without hormone therapy?

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Lu-PSMA-617 reduces disease progression versus deferred ADT in oligometastatic HSPC in phase 2 trialCan a targeted radiation drug delay prostate cancer progression without hormone therapy?

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