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The BULLSEYE trial is the second study to demonstrate that ¹⁷⁷Lu-PSMA works in hormone-sensitive prostate cancer – and the first to test it before starting hormone therapy.

Last year, the PSMAddition trial established that adding lutetium PSMA therapy to the standard combination of hormone therapy and androgen receptor inhibitors significantly delayed disease progression in metastatic hormone-sensitive prostate cancer. Now the BULLSEYE trial tested ¹⁷⁷Lu-PSMA at an even earlier stage of the disease than PSMAddition – before starting patients on hormone therapy and with only a few metastases present.

The Study

BULLSEYE (Phase II) enrolled 58 men with oligometastatic disease (≤5 metastases) who had already undergone prior radical treatment (surgery or radiotherapy) but now showed biochemical recurrence with a fast PSA doubling time (<6 months). Crucially, none of these patients had started ADT yet. They were randomized into two groups (29 intervention and 29 control) to receive either ¹⁷⁷Lu-PSMA (up to four cycles of 7.4 GBq every six weeks) or active monitoring with deferred hormone therapy – meaning the control group received no active treatment until their disease progressed. In other words, the trial tested ¹⁷⁷Lu-PSMA as a standalone treatment, compared against a strategy of “deferred ADT” or active monitoring until progression. The primary goal of the study was to prolong time without ADT.

PSMA PET/CT was used as a screening tool to confirm both the number of lesions and their level of PSMA expression. To ensure the therapy would be effective, patients were selected based on high PSMA expression, specifically requiring an SUVmax > 15.

The Results

The results were clear. The demonstrated delay in progression amounted to 25 months in the intervention group vs 5 months in the control one – a five-fold difference. Patients receiving lutetium PSMA therapy had a 93% lower risk of disease progression or death during the study period. ¹⁷⁷Lu-PSMA as a standalone treatment could durably delay the need for hormone therapy (ADT) in patients with a beginning metastatic spread.

Beyond delaying progression, 24% of patients in the intervention arm achieved complete biochemical remission – meaning their PSA became undetectable – a notable result for a disease that had already spread beyond the prostate.

Safety

The side effect profile in BULLSEYE was consistent with what is already well established for ¹⁷⁷Lu-PSMA. The most frequently reported effects in the treatment group were dry mouth (66%), fatigue (55%), and nausea (48%), the great majority of which were mild (grade 1). There were no grade 4 adverse events and no treatment-related deaths in the lutetium PSMA arm.

Takeaway

For patients, the most relevant takeaway is that BULLSEYE pushed PSMA radioligand therapy into an earlier disease stage and thereby delayed the ADT therapy replete with side effects.

In standard clinical practice, ADT is often started once metastases appear. But ADT comes with significant side effects: fatigue, hot flashes, bone thinning, and metabolic changes. Many patients understandably wish to delay these as long as possible, provided their cancer remains controlled.

The BULLSEYE trial showed that for PSMA-avid oligometastatic disease a course of ¹⁷⁷Lu-PSMA can buy a median of 20 additional months without hormone therapy, compared to simply watching and waiting. PSMA PET/CT was crucial as a screening tool, requiring an SUVmax >15 to ensure sufficient PSMA expression.

So, for patients with oligometastatic, PSMA-positive recurrence who have not yet started ADT, BULLSEYE provides evidence that radioligand therapy as a monotherapy can safely postpone ADT by many months, with a chance of complete biochemical remission in about one in four patients.

If you have been diagnosed with oligometastatic prostate cancer and are facing the initiation of hormone therapy, a PSMA PET/CT can determine whether PSMA radioligand therapy is a meaningful option for you. Contact our clinic to discuss whether this approach may be appropriate for your situation.

 

Comparison of PSMAddition and BULLSEYE

Feature	PSMAddition	BULLSEYE
Type	Phase III, Large scale: 1,144 patients, randomized	Phase II, Small scale: 58 patients, randomized
Trial Status	Completed primary analysis (reported Oct 2025)	Completed primary analysis (reported May 2025)
Disease stage	Metastatic HSPC	Oligometastatic HSPC (≤5 metastatic lesions), biochemical recurrence
Prior Treatment	ADT or ARPI started, but for no more than 45 days	Radical prostatectomy or radiotherapy
Disease tempo	No progression within 12 months of prior adjuvant/neo-adjuvant therapy; Rapidly progressing patients requiring docetaxel excluded	PSA doubling time <6 months; PSA >1.0 μg/L
PSMA Expression	At least one PSMA-expressing lesion	SUVmax > 15
Treatment Backbone	¹⁷⁷Lu-PSMA + ADT + ARPI	¹⁷⁷Lu-PSMA monotherapy vs. deferred ADT
Primary Goal	Improve radiographic PFS (rPFS)	Delay disease progression and ADT initiation
Primary Result	Met endpoint; 28% reduction in risk of progression/death	Met endpoint; significant delay in progression (25 vs 5 months) with 24% in complete biochemical remission

Bibliography:

1. Privé B, Noordzij W, Muselaers C et al.
   [¹⁷⁷Lu]Lu-PSMA-617 in oligometastatic hormone sensitive prostate cancer (BULLSEYE): an open-label, randomised, phase 2 study.
   The Lancet Oncology, 27, 461-469
2. Sayyid, R. K. (2025, June 3).
   ASCO 2025: Lutetium-177-PSMA-617 in Oligo-Metastatic Hormone Sensitive Prostate Cancer (BULLSEYE Trial).
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3. Privé BM, Noordzij W, Muselaers CHJ, et al.
   [¹⁷⁷Lu]-PSMA-617-PSMA-617 in oligometastatic hormone sensitive prostate cancer (BULLSEYE): an open-label, randomised, phase 2 study.
   Lancet Oncol. 2026 Apr;27(4):461-469.
4. Georgakopoulos A., Bamias A., Chatziioannou S.
   Current role of PSMA-PET imaging in the clinical management of prostate cancer..
   Ther Adv Med Oncol. 2023.
5. Sayyid, R. K. (2025, October 18).
   ESMO 2025: BULLSEYE: 177Lu-PSMA-617 in oligometastatic hormone sensitive prostate cancer.
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6. Tagawa, S. T. (2025, December 5).
   SUO 2025: PSMAddition: Top line results from a Phase 3 trial.
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