Hojjat Ahmadzadehfar1,2, Ralf Matern3, Richard P Baum4,5, Robert Seifert6,7, Katharina Kessel8, Martin Bögemann7,9, Clemens Kratochwil10, Hendrik Rathke10, Harun Ilhan11, Hanna Svirydenka12, Mike Sathekge13, Levent Kabasakal14, Anna Yordanova3,15, Francisco Osvaldo Garcia-Perez16, Kalevi Kairemo17, Masha Maharaj18, Diana Paez19, Irene Virgolini12, Kambiz Rahbar7,8. 1. Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany. hojjat.ahmadzadehfar@ruhr-uni-bochum.de. 2. Department of Nuclear Medicine, Klinikum Westfalen, Am Knappschaftskrankenhaus 1, 44309, Dortmund, Germany. hojjat.ahmadzadehfar@ruhr-uni-bochum.de. 3. Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany. 4. Center for Precision Radiomolecular Oncology, Bad Berka (ZBB), Germany. 5. Advanced Theranostics Center for Molecular Radiotherapy and Precision Oncology, ICPO Center of Excellence, CURANOSTICUM Wiesbaden-Frankfurt at DKD Helios Klinik, Wiesbaden, Germany. 6. Department of Nuclear Medicine, University Hospital Essen, Essen, Germany. 7. West German Cancer Center, Münster and Essen, Germany. 8. Department of Nuclear Medicine, University Hospital Münster, Münster, Germany. 9. Department of Urology, University Hospital Münster, Münster, Germany. 10. Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany. 11. Department of Nuclear Medicine, LMU, University Hospital Munich, Munich, Germany. 12. Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria. 13. Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Pretoria, South Africa. 14. Department of Nuclear Medicine, Istanbul University, Istanbul, Turkey. 15. Department of Radiology, Marienhospital Bonn, Bonn, Germany. 16. Department of Nuclear Medicine and Molecular Imaging, Instituto Nacional de Cancerología, Mexico City, Mexico. 17. Docrates Cancer Center, Helsinki, Finland. 18. Department of Nuclear Medicine, Imaging and Therapy Centre, Durban, KwaZulu-Natal, South Africa. 19. Nuclear Medicine and Diagnostic Imaging Section, Department of Nuclear Sciences and Applications, IAEA, Vienna, Austria.
Abstract
INTRODUCTION: Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement. METHODS: The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [177Lu]Lu-PSMA-617 and a follow-up of at least 6 months. Tumour burden in the bone was classified prior to RLT as follows: less than 6 lesions, 6-20 lesions, more than 20 lesions and diffuse involvement. The response rate was evaluated using changes of the prostate-specific antigen (PSA) after the first treatment cycle. Overall survival was calculated from the date of the first treatment. Haematological adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. RESULTS: A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6-20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (p < 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6-20 lesions (OS: 16 vs. 12 months; p = 0.038) as well as diffuse involvement (OS: 11 vs. 7 months; p = 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with <6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases: p < 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia. CONCLUSION: The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.
INTRODUCTION: Prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) showed in a multicentre WARMTH (World Association of Radiopharmaceutical and Molecular Therapy) study that the presence of bone metastases is a negative prognosticator for the survival. The current multicentre retrospective analysis aims to evaluate the response rate to RLT, the overall survival (OS) of patients and the safety of the treatment according to the extent of bone involvement. METHODS: The study included patients with progressive metastatic castration-resistant prostate cancer (mCRPC), who underwent RLT with [177Lu]Lu-PSMA-617 and a follow-up of at least 6 months. Tumour burden in the bone was classified prior to RLT as follows: less than 6 lesions, 6-20 lesions, more than 20 lesions and diffuse involvement. The response rate was evaluated using changes of the prostate-specific antigen (PSA) after the first treatment cycle. Overall survival was calculated from the date of the first treatment. Haematological adverse events were classified according to Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. RESULTS: A total of 319 males were included in the analysis. The extent of bone metastases and PSA response did not correlate significantly. Any PSA decline was observed in 73% patients; 44% showed a decline of ≥50%. The median OS of patient in the different subgroups was 18 months (less than 6 lesions), 13 months (6-20 lesions), 11 months (more than 20 lesions) and 8 months (diffuse involvement), respectively (p < 0.0001). Patients with prior Ra-223-therapy showed longer OS in all subgroups, especially in the subgroups with 6-20 lesions (OS: 16 vs. 12 months; p = 0.038) as well as diffuse involvement (OS: 11 vs. 7 months; p = 0.034). Significant negative prognosticators of OS were the existence of liver metastases in all subgroups and prior chemotherapy in patients with <6 bone lesions. Anaemia and thrombocytopenia correlated positively with the extent of bone metastases: p < 0.0001 and 0.005, respectively. No patient showed a high grade leukopenia. CONCLUSION: The extent of bone involvement correlated negatively with the OS after RLT; however, it showed no relevant correlation with the PSA response rate. Prior therapy with Ra-223 may have a positive impact on OS. Haematotoxicity was higher in patients with more than 20 bone lesions; nevertheless, the majority of these patients did not show a relevant haematotoxicity.
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