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  • Author
    Vishnu Murthy
  • PI

    Andrei Gafita, MD

  • Co-Author

    Johannes Czernin, Michael Hofman, Wolfgang Fendler, Louise Emmett, Clemens Kratochwil, Matthias Eiber, Ida Sonni, Matthias Benz, Thomas Hope, Andrea Farolfi, Irene Burger, Jérémie Calais, Masatoshi Hotta

  • Title

    Predicting Outcomes of Metastatic Castrate-Resistant Prostate Cancer Patients after Lutetium-177 PSMA Radioligand Therapy

  • Program


  • Other Program (if not listed above)

  • Abstract


    To develop standardized patient selection criteria for Lutetium-177 (177Lu) Prostate-Specific Membrane Antigen (PSMA) Radioligand Therapy (RLT) using quantitative and qualitative analysis of baseline PSMA PET imaging.



    Prostate cancer patients with metastatic disease who continue to experience disease progression on hormone therapy are classified as metastatic castrate-resistant prostate cancer (mCRPC). 177Lu-PSMA RLT significantly prolongs progression-free survival (PFS) and overall survival (OS) in mCRPC patients compared to standard of care alone. However, there are currently no standardized patient selection criteria for 177Lu-PSMA RLT using baseline PSMA PET imaging. 



    Retrospective analysis was performed using an international, multicentric dataset (N = 236). Patients were treated with 6.0-8.5 GBq of 177Lu-PSMA RLT between October 2014 and December 2018 across six sites and had available screening 68Ga-PSMA-11 PET/CT scans within ten weeks of treatment. This research project comprised of three steps: i) quantitative analysis of PSMA PET tumor expression and determination of associations with OS and PFS ii) development of a visual grading system of PSMA PET tumor expression and determination of inter-reader agreement and associations with OS and PFS and iii) determining agreement between quantitative and qualitative analysis.



    Patients with high tumor-to-salivary gland uptake ratios on baseline PSMA PET imaging had significantly longer PFS compared to patients with intermediate and low tumor-to-salivary gland uptake ratios (median PFS: 1.8 vs. 4.0 vs. 7.7 months; p < 0.001) but similar OS (median OS: 14 vs. 11.4 vs. 14.3 months; p = 0.055). Patients with high majority scores on the visual grading system had similar PFS compared to patients with intermediate and low majority scores (median PFS: 4.8 vs. 4.0 vs. 4.8 months; p = 0.69) and similar OS (median OS: 11.4 vs. 12.8 vs. 13.7 months; p = 0.78). The Fleiss multi-rater κ statistic for inter-reader agreement using the visual grading system was 0.51 (0.47-0.56), while the Fleiss multi-rater κ statistic for agreement between groupings based on quantitative analysis and qualitative analysis was 0.07 (-0.13-0.162).



    Tumor-to-salivary gland uptake ratios calculated using quantitative analysis of baseline PSMA PET imaging can be useful to identify non-responders to 177Lu-PSMA RLT. The low inter-reader agreement of the visual grading system and low concordance with results from quantitative analysis suggest that this system has limited clinical utility and cannot serve as a surrogate for quantitative data. The prognostic value of baseline PSMA PET imaging for outcome following 177Lu-PSMA RLT requires further investigation.

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