Radioligand Plus Radiation Delays Prostate Cancer Progression to 17.6 Months

Patients with recurrent prostate cancer lived longer without their cancer worsening when they received a targeted radioligand therapy before radiation, according to findings from the phase 2 LUNAR trial.

The trial added 177Lu-PNT2002 to stereotactic body radiation therapy (SBRT) and found that median progression-free survival (the length of time before the cancer grew or spread) reached 17.6 months with the combination, compared with 7.4 months with SBRT alone, according to the original results published in the Journal of Clinical Oncology.

An updated analysis published in European Urology found that after a median follow-up of 31.9 months, patients receiving the combination had a 62% lower risk of disease progression, starting additional hormone therapy or death than patients receiving SBRT alone. The update also showed early signs that the combination may lower the risk of cancer spreading more widely or becoming resistant to hormone therapy.

“Our earlier findings showed that adding 177Lu-PNT2002 could significantly delay progression and the need for hormone therapy,” said Dr. Amar Kishan, first author of the study at the David Geffen School of Medicine at UCLA.

What did the LUNAR trial show in recurrent prostate cancer?

The combination also delayed the need for additional hormone therapy in the initial analysis. Patients receiving 177Lu-PNT2002 and SBRT went a median of 24.3 months before starting hormone therapy, compared with 14.1 months for patients receiving SBRT alone.

With longer follow-up, the benefits continued. More patients in the combination group had no detectable cancer at two years (33%) than in the SBRT-alone group (12%).

Researchers also tracked whether patients developed more widespread cancer or castration-resistant prostate cancer, which occurs when cancer continues to grow despite treatments that lower testosterone levels. Three patients in the combination group developed more than five new cancer sites, compared with nine patients in the SBRT-alone group. One patient in the combination group developed castration-resistant prostate cancer, compared with seven patients in the SBRT-alone group.

“But with longer follow-up, we’re seeing signs that the benefit may extend beyond simply delaying recurrence, including a potential reduction in the risk of widespread disease and cancer that no longer responds to hormone therapy,” Kishan explained.

However, the findings on widespread and hormone-resistant prostate cancer were exploratory and require confirmation in larger studies.

How was the phase 2 LUNAR trial designed?

The trial included 92 patients with oligorecurrent hormone-sensitive prostate cancer, meaning their cancer had returned in one to five locations after previous treatment and still responded to hormone therapy. Patients were randomly assigned to receive SBRT alone or two cycles of 177Lu-PNT2002 followed by SBRT.

SBRT delivers high doses of radiation directly to tumors while limiting exposure to surrounding healthy tissue. 177Lu-PNT2002 works differently: it travels through the bloodstream and targets prostate-specific membrane antigen (PSMA), a protein commonly found on prostate cancer cells. Researchers paired the two treatments to see whether they could control visible tumors while also reaching cancer cells elsewhere in the body that may be too small to detect on imaging scans.

The initial analysis followed patients for a median of 22 months. The updated analysis extended follow-up to nearly three years.

Did 177Lu-PNT2002 raise new safety concerns in the LUNAR trial?

Researchers reported no new safety concerns during the longer follow-up period.

What do the LUNAR trial results mean for patients with recurrent prostate cancer?

For patients whose prostate cancer returns in only a few locations, SBRT can target visible tumors. However, cancer cells may remain elsewhere in the body at levels too small to detect with sensitive imaging.

The LUNAR findings suggest that pairing SBRT with 177Lu-PNT2002 may treat both the visible tumors and the cancer cells that imaging has not picked up. The combination may also help some patients delay hormone therapy, which can control prostate cancer but may cause side effects that affect quality of life.

“We may be able to treat cancer cells that are present elsewhere in the body but are too small to detect, while giving patients more time before they need hormone therapy,” Kishan said.

The researchers noted that the trial was conducted at a single institution with a relatively small number of patients. They also noted that it was not designed to definitively establish whether the combination prevents widespread or hormone-resistant prostate cancer. It is too early to determine whether the treatment improves overall survival (how long patients live).

“This is an important step toward understanding whether we can use these treatments earlier, when the amount of cancer in the body is still relatively small,” Kishan said.

Further research is needed to confirm the results and determine which patients with recurrent prostate cancer may benefit most from the combination.

References

1. Kishan AU, et al. “177Lu-Prostate-Specific Membrane Antigen Neoadjuvant to Stereotactic Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR): An Open-Label, Randomized, Controlled, Phase II Study.” Journal of Clinical Oncology. Published November 12, 2025.
2. Kishan AU, et al. “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.” European Urology. 2026.
3. News release. “Targeted radioactive therapy may help delay spread of recurrent prostate cancer, UCLA study suggests.” UCLA Health. Posted: October 12, 2026.

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