PSMA-guided radiotherapy intensification: primary endpoint missed, signal in high-risk and post-prostatectomy men

Design

Phase 2, two-centre, open-label randomised trial

Population

253 men due for radiotherapy for prostate cancer across four strata

Primary outcome

Five-year failure-free survival

Effect

66% vs 62%; HR 0.80 (one-sided 90% CI upper bound 1.04), not significant

PSMAgRT was a two-centre, open-label phase 2 trial that randomised 262 men due for standard radiotherapy for prostate cancer to standard treatment or to radiotherapy intensified to every site detected on PSMA-PET. Four strata were included: salvage after prostatectomy, high-risk primary disease, oligometastatic disease and salvage after previous radiotherapy. Median follow-up for the 253 analysed was 66 months.

Five-year failure-free survival, the primary endpoint, was 66% with PSMA-guided treatment and 62% with standard care (HR 0.80), which did not meet the trial's prespecified threshold. Freedom from biochemical progression favoured PSMA guidance overall (72% vs 65%), and more so in the high-risk (81% vs 66%) and post-prostatectomy (80% vs 68%) strata. Only one grade 3 or higher event was possibly related to dose escalation.

The positive results are secondary and subgroup findings in a heterogeneous phase 2 trial, and some rely on a one-sided threshold. They are the basis for the phase 3 PATRON trial in those two groups.

For now, PSMA-PET is useful for staging, but intensifying radiotherapy to every PSMA-avid site has not been shown to improve the primary outcome. Where PSMA-PET is available in India, mostly in larger centres, it should be used within established indications.

• Do not treat PSMA-guided dose intensification as proven; the primary endpoint was not met.
• Note the biochemical signal in high-risk and post-prostatectomy men, pending phase 3 results.
• Use PSMA-PET within established staging indications.
• Consider referral to trials of PSMA-guided treatment where available.

Why it matters

Better detection does not automatically mean better outcomes, and this trial shows how hard that step is to prove.

Don't overread it

The primary endpoint was negative; the favourable subgroup results need confirmation in phase 3.

The statistics, in plain English

A hazard ratio of 0.80 suggests a possible 20% reduction in failure, but the trial could not exclude no effect. Subgroup results, and those judged on a one-sided threshold, are weaker evidence than the primary analysis and are hypothesis-generating.

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