PSMA-PET for improved risk assessment in patients with metastatic prostate cancer

• Applicants: Professor Dr. Wolfgang Fendler; Professor Dr. Kambiz Rahbar
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 564651276

Next generation Positron-Emission-Tomography (PET) imaging directed at the Prostate-Specific Membrane Antigen (PSMA) was introduced in 2011 by the University of Heidelberg for whole-body staging of prostate cancer. Since then, PSMA-PET was implemented first in German nuclear medicine clinics followed by worldwide adoption. We previously demonstrated that PSMA-PET detects the extent of prostate cancer with higher accuracy than conventional imaging in patients with primary disease and biochemical recurrence as well as non-metastatic and metastatic castration-resistant disease (1-3). Our findings led to FDA approval in December 2020 and supported EMA approval in December 2022 (4). Furthermore, we have demonstrated that PSMA-PET disease extent negatively correlates with outcome (5,6). However, the extent of such association and applicability for different stages of metastatic prostate cancer is yet unclear. Despite extensive literature on diagnostic accuracy, the association of PSMA-PET findings with long-term clinical outcome in patients with metastatic hormone-sensitive (mHSPC) or castration-resistant (mCRPC) prostate cancer has not been assessed in a large patient cohorts yet. There is an urgent need for improved prognostication of metastatic prostate cancer survival for personalized treatment guidance. Until now, outcome analysis was not possible with sufficient power due to missing long-term follow-up data. Due to early adoption in clinical routine, the University Hospitals in Essen und Münster have now reached 5-year and longer survival follow-up for more than 1500 patients who underwent PSMA-PET for metastatic prostate cancer until 2019. This patient cohort is large enough to address the urgent need for improved prognostication. We will assess the prognostic value of stage and total tumor volume from PSMA-PET as well as molecular and clinical parameters in a large retrospective imaging database. We will further analyze the prognostic value of novel metrics of PSMA-PET, including regional sub-volumes, heterogeneity or lesion distance to develop a combined clinical and imaging nomogram for the prediction of overall survival for mHSPC and mCRPC (Aim 1). Further, we will establish patient dataset inclusion through an international PROMISE registry study, with central image analysis, for independent validation of the nomogram (Aim 2). Based on a uniquely large patient cohort in Essen and Münster with follow-up of 5 years and longer, this project will assess the prognostic value of PSMA-PET, including novel imaging metrics, in patients with mHSPC or mCRPC (Aim 1). Imaging will be combined with molecular and clinical parameters to achieve highest prognostic accuracy and to be validated in an independent international patient cohort (Aim 2).

• DFG Programme: Research Grants