Lutetium-PSMA before stereotactic radiotherapy: longer progression-free survival in oligorecurrent disease

Design

Randomised phase 2 trial, 1:1, extended follow-up

Population

92 patients with PSMA PET-detected oligorecurrent hormone-sensitive prostate cancer (1 to 5 lesions)

Primary outcome

Progression-free survival (new PSMA PET lesions, salvage hormonal therapy, or death)

Effect

Median 17.6 vs 7.4 months; HR 0.38 (95% CI 0.23 to 0.61)

In the randomised phase 2 LUNAR trial, 92 patients with PSMA PET/CT-detected oligorecurrent hormone-sensitive prostate cancer and one to five lesions suitable for stereotactic body radiotherapy (SBRT) were assigned 1:1 to SBRT alone (47) or two cycles of neoadjuvant 177Lu-PNT2002 followed by SBRT (45). Progression-free survival was defined by new PSMA PET lesions, starting salvage hormonal therapy, or death.

At a median follow-up of 31.9 months, median progression-free survival was 17.6 months against 7.4 (HR 0.38, 95% CI 0.23 to 0.61). Hormonal therapy-free survival also favoured the combination (HR 0.57, 0.34 to 0.95). Exploratory endpoints such as polymetastatic progression, castration-resistant disease-free survival and conventional imaging progression pointed the same way, though the intervals included or approached 1.0 (for example HR 0.28, 0.08 to 1.03). No new safety signals appeared.

The trial is small, phase 2 and used a PSMA PET-based endpoint that depends on scan sensitivity. It does not show overall survival benefit. Radioligand therapy before SBRT is investigational and not a standard of care.

• Treat the combination as investigational until phase 3 data and regulatory approval are available.
• Consider trial referral for patients with PSMA PET-detected oligorecurrence.
• Note that the primary endpoint depended on new lesions on PSMA PET, a more sensitive measure than conventional imaging.
• Remember overall survival and quality-of-life data are not yet available.
• Check local availability of radioligand therapy, which is limited in India.

Why it matters

It raises the possibility that systemic radioligand therapy could change the course of oligorecurrent disease, not only treat visible lesions.

Don't overread it

A phase 2 trial with PSMA PET-defined progression has not shown benefit on survival or symptoms, and exploratory endpoints are hypothesis-generating.

The statistics, in plain English

A hazard ratio of 0.38 means that at any point the combination group had about 38% of the hazard of progression, but with 92 patients the interval (0.23 to 0.61) is still fairly wide. Intervals for the exploratory endpoints touch or cross 1.0, so those results are hypothesis-generating at best.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.