ORIOLE

ORIOLE randomised 54 men with recurrent hormone-sensitive prostate cancer and one to three metastases on conventional imaging, 36 to stereotactic ablative radiotherapy and 18 to observation. Progression was defined by PSA rise, progression on conventional imaging, symptomatic progression, start of androgen deprivation for any reason, or death.

Progression at 6 months occurred in 7 of 36 men (19 percent) after radiotherapy and 11 of 18 (61 percent) under observation (p=0.005). Median progression-free survival was not reached with radiotherapy against 5.8 months with observation, hazard ratio 0.30 (95 percent confidence interval 0.11 to 0.81, p=0.002). No toxic effects of grade 3 or greater were observed.

The finding that made ORIOLE more than a small positive trial is the imaging one. Men had PSMA PET that was not used for treatment planning, and total consolidation of all PSMA-avid disease reduced the risk of new lesions at 6 months from 63 to 16 percent (p=0.006). Treating what conventional imaging can see, while leaving what it cannot, is much less effective than treating everything.

T-cell receptor sequencing showed significant clonotypic expansion after radiotherapy, and baseline clonality correlated with progression in the radiotherapy arm only, evidence that the effect is partly immunological. These are exploratory findings in 54 men and should be read as hypotheses.