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Combining PSMA-PET and PROMISE to Re-Define Disease Stage and Risk in Patients with Prostate Cancer: A Multicentre Retrospective Study - Beyond the Abstract

Prostate-specific membrane antigen targeting PET (PSMA-PET), the latest molecular imaging advancement for prostate cancer, greatly improved staging accuracy. Since its introduction for clinical use in 2012,1 conventional imaging is increasingly replaced by PSMA-PET, which has led to a shift in nearly all disease stages.2-4 Systematic upstaging comes with challenges for ongoing and future studies and clinical management, as current evidence largely builds on conventional imaging.

A system to standardize PSMA-PET stage reports, the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) framework, was introduced in 2018 and updated in 2023.5, 6 This system was developed to categorize clinically relevant stages of prostate cancer. Since its introduction, it has been unclear if PSMA-PET and PROMISE are associated with patient survival. Understanding the association between the PSMA-PET stage and survival is paramount to defining novel risk groups for future study design and guideline recommendations.

Now, more than 10 years after the introduction of PSMA-PET, several sites with early adoption of PSMA-PET in Germany were able to confirm PSMA-PET and PROMISE as a novel prognostic biomarker for prostate cancer.7 Two nomograms were established to predict pan-stage overall survival based on PSMA-PET and PROMISE metrics. The simple visual nomogram can be applied at any PSMA-PET facility using any imaging software, while the quantitative nomogram includes PSMA-PET tumor volume and respective average uptake (SUVmean) (Figure). Head-to-head comparison to established clinical risk scores confirms superior prognostic accuracy of PSMA-PET nomograms in the early and late stages of the disease. However, the added value of PSMA-PET nomograms is not yet high enough to enable individual patient counseling.

Prognostic PSMA-PET PROMISE Metrics to Predict Overall Survival in Patients with Prostate Cancer
Figure: Prognostic PSMA-PET PROMISE Metrics to Predict Overall Survival in Patients with Prostate Cancer

Our international multicentric PROMISE-PET Registry Study (promise-pet.org, NCT06320223) will deliver ongoing improvement of the nomograms in the future.

Written by: Madeleine J. Karpinski MSc & Wolfgang P. Fendler MD

Department of Nuclear Medicine, University Hospital Essen, Essen, Germany

References:

  1. Eder M, Schäfer M, Bauder-Wüst U, Hull W-E, Wängler C, Mier W, et al. 68Ga-Complex Lipophilicity and the Targeting Property of a Urea-Based PSMA Inhibitor for PET Imaging. Bioconjugate Chemistry. 2012;23(4):688-97.
  2. Fendler WP, Calais J, Eiber M, Flavell RR, Mishoe A, Feng FY, et al. Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial. JAMA Oncol. 2019;5(6):856-63.
  3. Fendler WP, Weber M, Iravani A, Hofman MS, Calais J, Czernin J, et al. Prostate-Specific Membrane Antigen Ligand Positron Emission Tomography in Men with Nonmetastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2019;25(24):7448-54.
  4. Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet. 2020;395(10231):1208-16.
  5. Eiber M, Herrmann K, Calais J, Hadaschik B, Giesel FL, Hartenbach M, et al. Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE): Proposed miTNM Classification for the Interpretation of PSMA-Ligand PET/CT. J Nucl Med. 2018;59(3):469-78.
  6. Seifert R, Emmett L, Rowe SP, Herrmann K, Hadaschik B, Calais J, et al. Second Version of the Prostate Cancer Molecular Imaging Standardized Evaluation Framework Including Response Evaluation for Clinical Trials (PROMISE V2). Eur Urol. 2023;83(5):405-12.
  7. Karpinski MJ, Husing J, Claassen K, Moller L, Kajuter H, Oesterling F, et al. Combining PSMA-PET and PROMISE to re-define disease stage and risk in patients with prostate cancer: a multicentre retrospective study. Lancet Oncol. 2024.
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