PSMA-guided radiotherapy did not improve failure-free survival at five years, but may help selected strata

Design

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

Population

253 men with prostate cancer planned for radiotherapy across four strata

Primary outcome

Failure-free survival at 5 years

Effect

66% vs 62%, HR 0.80 (not significant); biochemical control 72% vs 65%

The phase 2 PSMAgRT trial, published in European Urology on 3 October, randomised 262 men due for standard radiotherapy to standard care or to radiotherapy intensified to every site detected on PSMA PET. There were four strata: salvage after prostatectomy, high-risk primary disease, oligometastatic disease and salvage after radiotherapy. 253 were analysed with a median follow-up of 66 months.

Five-year failure-free survival — the primary endpoint — was 66% with PSMA guidance and 62% with standard care (HR 0.80; not significant at the prespecified one-sided threshold). Freedom from biochemical progression favoured PSMA guidance overall (72% vs 65%) and more clearly in the post-prostatectomy (80% vs 68%) and high-risk (81% vs 66%) strata. Only one grade 3 or worse event was possibly related to dose escalation.

The primary endpoint was missed, and the stratum-level gains are secondary or post hoc in a small, mixed population. The phase 3 PATRON trial is testing exactly those groups. Until it reports, PSMA PET is a staging tool that can change radiotherapy fields, without proof that doing so improves survival.

• Do not promise patients that PSMA-guided radiotherapy improves long-term outcomes; the primary endpoint was not met.
• Consider PSMA PET findings when planning salvage radiotherapy after prostatectomy, where the signal was strongest.
• Expect little added toxicity from PSMA-guided dose escalation, based on this trial.
• Watch for the phase 3 PATRON results before changing standard practice.

Why it matters

PSMA PET is spreading faster than the evidence that acting on it changes outcomes.

Don't overread it

The benefits are in secondary and post hoc subgroup analyses of a phase 2 trial.

The statistics, in plain English

The trial used a one-sided significance threshold of 0.10, more lenient than usual, and still missed the primary endpoint (p = 0.14). Subgroup results with wide intervals are hypotheses for the phase 3 trial, not conclusions.

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