Stage Migration on Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Comparison to Conventional Imaging in Patients with High-risk Prostate Cancer Referred for Radiation Therapy: Results from the Phase 2/3 THUNDER Trial.

Background and objective: In high-risk prostate cancer, the proPSMA trial showed upstaging with prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in 14% of patients. We hypothesised that the probability of stage migration in a patient population referred for curative-intent radiotherapy would be higher. Here we report stage migration results according to PSMA PET/CT in the first year of inclusion in the phase 2/3 THUNDER trial (NCT06282588).

Methods: Patients with high-risk prostate cancer screened between December 2023 and December 2024 in the THUNDER trial with both conventional imaging (CT, bone scintigraphy) and PSMA PET/CT within 16 weeks before screening were included (n = 142). Stage migration according to the TNM classification versus the molecular imaging (miTNM) classification (PROMISE v2 criteria) was assessed using descriptive statistics.

Key findings and limitations: PSMA PET/CT led to stage migration in 43 patients, of whom 42 (30%) were upstaged and one (1%) was downstaged. Upstaging to miN1-2 disease occurred in 32 patients (23%), and to miM1a-c disease in 19 patients (13%). The probability of upstaging increased with the number of high-risk features. In the subgroup meeting the STAMPEDE M0 high-risk criteria (n = 73), PSMA PET/CT upstaged 27 patients (37%), including upstaging to miM1a-c disease in 14 (19%). Limitations include the absence of central review of the imaging procedures.

Conclusions and clinical implications: One-third of patients with high-risk prostate cancer referred for curative-intent radiotherapy were upstaged on PSMA PET/CT. This finding supports the use of PSMA PET/CT for staging, especially in patients with multiple high-risk features, and suggests a need for treatment adaptations accordingly, which will be further investigated in the THUNDER trial.