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

Fleur Kleiburg ¹, Piet Dirix ², Valérie Fonteyne ³

¹Department of Radiology, Section of Nuclear Medicine, Leiden University Medical Center, Leiden, The Netherlands; Biomedical Photonic Imaging Group, University of Twente, Enschede, The Netherlands.
²Department of Radiation Oncology, Iridium Network, Antwerp, Belgium.
³Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium.
⁴Department of Radiation Oncology, AZORG, Aalst, Belgium.
⁵Department of Urology, VITAZ, Sint-Niklaas, Belgium.
⁶Department of Medical Oncology, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
⁷Department of Radiation Oncology, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
⁸Department of Radiation Oncology, AZ Groeninge, Kortrijk, Belgium.
⁹Department of Medical Oncology, Centres Hospitaliers Universitaires HELORA, La Louvière, Belgium.
¹⁰Department of Radiation Oncology, AZ Sint-Jan, Bruges, Belgium.
¹¹Department of Radiation Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
¹²Department of Radiation Oncology, Institut Jules Bordet, Brussels, Belgium.
¹³Department of Radiation Oncology, AZ Delta, Roeselare, Belgium.
¹⁴Department of Urology, ZAS, Antwerp, Belgium.
¹⁵Department of Medical Oncology, ZAS, Antwerp, Belgium.
¹⁶Department of Nuclear Medicine, ZAS, Antwerp, Belgium.
¹⁷Department of Nuclear Medicine, UZ Leuven, Leuven, Belgium.
¹⁸Department of Nuclear Medicine and Oncological Imaging, Centre Hospitalier Universitaire de Liège, Liège, Belgium.

⁰Department of Radiology, Section of Nuclear Medicine, Leiden University Medical Center, Leiden, The Netherlands; Biomedical Photonic Imaging Group, University of Twente, Enschede, The Netherlands.

European Urology Oncology +

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September 25, 2025

View abstract on PubMed

Summary

Prostate-specific membrane antigen (PSMA) PET/CT upstaged one-third of high-risk prostate cancer patients undergoing radiotherapy. This molecular imaging supports treatment adaptation, particularly for those with multiple high-risk features.

Area Of Science

Oncology
Radiology
Nuclear Medicine

Background

High-risk prostate cancer requires accurate staging for curative-intent radiotherapy.
Previous studies like proPSMA indicated upstaging in 14% of patients with prostate-specific membrane antigen (PSMA) PET/CT.
The THUNDER trial hypothesised higher stage migration rates in patients referred for radiotherapy.

Purpose Of The Study

To evaluate stage migration using PSMA PET/CT in high-risk prostate cancer patients undergoing curative-intent radiotherapy.
To compare TNM classification with molecular imaging TNM (miTNM) classification based on PSMA PET/CT findings.
To determine the probability of upstaging and downstaging in this patient cohort.

Main Methods

Included 142 patients with high-risk prostate cancer from the THUNDER trial (NCT06282588).
Patients underwent both conventional imaging (CT, bone scintigraphy) and PSMA PET/CT within 16 weeks prior to screening.
Stage migration was assessed using descriptive statistics comparing TNM and miTNM (PROMISE v2 criteria).

Main Results

PSMA PET/CT resulted in stage migration in 43 patients (30%), with 42 (30%) upstaged and 1 (1%) downstaged.
Upstaging to regional lymph node metastasis (miN1-2) occurred in 32 patients (23%).
Distant metastasis (miM1a-c) was identified in 19 patients (13%), with higher upstaging rates in patients with multiple high-risk features.

Conclusions

PSMA PET/CT upstaged approximately one-third of high-risk prostate cancer patients referred for radiotherapy.
Findings support PSMA PET/CT for staging in this population, especially with multiple risk factors.
Treatment adaptations based on PSMA PET/CT staging are suggested and will be explored further in the THUNDER trial.

Keywords:

High-risk prostate cancer Positron emission tomography/computed tomography Prostate-specific membrane antigen Stage migration