177Lu-Prostate-specific Membrane Antigen Prior to Stereotactic Ablative Radiotherapy in Oligorecurrent Prostate Cancer: Secondary and Exploratory End Point Results from the Randomized Phase 2 LUNAR Trial
In brief
Lutetium-177 before radiation extends median progression-free survival from 7.4 to 17.6 months
In a randomized phase 2 trial of 92 men with recurrent prostate cancer limited to one to five metastases, two cycles of lutetium-177 therapy before targeted radiation extended median progression-free survival from 7.4 to 17.6 months and delayed hormonal therapy. With about 32 months of follow-up, no new safety signals emerged, but benefits on other measures remain exploratory.
- Journal
- European urology (Q1)
- Published
- 12 October 2026
- Study design
- Phase 2 randomized trial (exploratory)
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Amar U Kishan, Holly Wilhalme, Carol Felix, Johanna Enke, Farzana Z Ali, Rejah Nabong, et al.
- PMID
- 42864228
- DOI
- 10.1016/j.eururo.2026.09.005
Why clinicians should know about it
- Picked for Radiology, Radiation Oncology, Nuclear Medicine, Medical Physics and Imaging (paper of the day, 14 October 2026): Neoadjuvant 177Lu‑PSMA before SBRT in oligorecurrent prostate cancer – combines
Abstract
The phase 2 randomized LUNAR trial previously demonstrated that neoadjuvant 177Lu-PNT2002 before stereotactic body radiotherapy (SBRT) significantly improved progression-free survival (PFS) in patients with oligorecurrent hormone-sensitive prostate cancer (orHSPC). We report updated efficacy and safety outcomes with extended follow-up. Patients with prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-detected orHSPC and one to five metastatic lesions amenable to SBRT were randomized 1:1 to SBRT alone or two cycles of neoadjuvant 177Lu-PNT2002 followed by SBRT. The primary end point was PFS, defined as new lesions on PSMA PET/CT, initiation of salvage hormonal therapy, or death. Secondary end points included hormonal therapy-free survival (HT-FS) and 24-mo progression-free status. Exploratory end points included polymetastatic PFS (poly-PFS), castration-resistant disease-free survival (CRFS), and conventional imaging progression-free survival (CT-PFS). Between September 2022 and November 2023, 92 patients were randomized to SBRT alone (n = 47) or 177Lu-PNT2002 plus SBRT (n = 45). At a median follow-up of 31.9 mo, 177Lu-PNT2002 significantly improved PFS (median 17.6 vs 7.4 mo; hazard ratio [HR] 0.38, 95% confidence interval [CI] = 0.23-0.61; p < 0.001) and HT-FS (HR 0.57, 95% CI = 0.34-0.95; p = 0.03). Exploratory analyses demonstrated improved poly-PFS (HR 0.28, 95% CI = 0.08-1.03; p = 0.04), CRFS (HR 0.13, 95% CI = 0.02-1.10; p = 0.03), and CT-PFS (HR 0.46, 95% CI = 0.19-1.09; p = 0.07). No new safety signals were observed. With extended follow-up, neoadjuvant 177Lu-PNT2002 before SBRT produced durable improvements in PFS and HT-FS. While poly-PFS, CRFS, and CT-PFS were exploratory end points, their improvement provides hypothesis-generating evidence that the addition of radioligand therapy to SBRT may alter disease trajectory beyond delaying PSMA PET/CT-detected recurrence.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.