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OtherClinical Investigations (Human)
Open Access

PREDICTORS OF OVERALL AND DISEASE FREE SURVIVAL IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER PATIENTS RECEIVING 225Ac-PSMA-617 RADIOLIGAND THERAPY

Mike Sathekge, Frank Bruchertseifer, Mariza Vorster, Ismaheel Lawal, Otto Knoesen, Johncy Mahapane, Cindy Davis, Florette Reyneke, Alex Maes, Clemens Kratochwil, Thabo Lengana, Frederik Giesel, Christophe Van de Wiele and Alfred Morgenstern
Journal of Nuclear Medicine May 2019, jnumed.119.229229; DOI: https://doi.org/10.2967/jnumed.119.229229
Mike Sathekge
1 University of Pretoria, South Africa;
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Frank Bruchertseifer
2 European Commission, Joint Research Centre, Germany;
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Mariza Vorster
1 University of Pretoria, South Africa;
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Ismaheel Lawal
1 University of Pretoria, South Africa;
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Otto Knoesen
3 Nuclear Technology Products (NTP), South Africa;
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Johncy Mahapane
1 University of Pretoria, South Africa;
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Cindy Davis
1 University of Pretoria, South Africa;
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Florette Reyneke
1 University of Pretoria, South Africa;
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Alex Maes
4 Katholieke UniversityLeuven, Belgium;
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Clemens Kratochwil
5 University Hospital Heidelberg, Germany;
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Thabo Lengana
1 University of Pretoria, South Africa;
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Frederik Giesel
5 University Hospital Heidelberg, Germany;
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Christophe Van de Wiele
6 Ghent University, Belgium
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Alfred Morgenstern
3 Nuclear Technology Products (NTP), South Africa;
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Abstract

Background: Metastatic prostate carcinoma over-expresses the prostate specific membrane antigen (PSMA) making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience in a series of 73 castrate resistant prostate carcinoma patients treated with 225Ac-PSMA-617, identifying variables predictive for overall and progression free survival following 225Ac-PSMA-617 treatment. Methods: 225Ac-PSMA-617 was administered to patients with mCRPC who had exhausted available therapy options for their disease. Full blood count, glomerular filtration rate and liver function test were obtained at baseline and on follow-up for evaluation of toxicity. 68Ga-PSMA PET/CT was obtained at baseline, prior to every treatment cycle and on follow-up for patients’ selection for treatment, to determine the activity of treatment agent to be adminsitered and for response assessment. Serial (prostate specific antigen) PSA was obatianed for PSA response assessment. Results: Seventy-three men (mean age=69 years, range:45-85) with mCRPC were treated with 210 cycles of 225Ac-PSMA-617. In 70% of patients, a PSA decline of ≥50% was obtained while 83% of patients had any PSA decline. In 29% of patients, all lesions on 68Ga-PSMA-PET resolved in response to treatment. During follow-up, 23 patients experienced disease progression while 13 patients died from their disease. The estimated median progression free survival (PFS) and overall survival (OS) were 15.2 months (95% CI: 13.1 – 17.4) and 18 months (95% CI: 16.2 – 19.9) respectively. On univariate analyses factors such as baseline PSA, any PSA decline, PSA decline ≥50%, prior chemotherapy, prior radiation therapy, baseline hemoglobin level were associated with longer PFS and OS (all p<0.05). On multivariate analyses, only prior Lu-PSMA therapy and a PSA decline ≥50% remained significant in their association with a longer PFS while only PSA decline ≥50% remained significantly associated with OS. Xerostomia was seen in 85% of patients, none was severe enough to warrant discontinuing treatment. Anaemia was seen in 27 patients, no patients with grade IV bone marrow toxicity was seen. Renal failure grade III-IV was seen in five patients with baseline renal impairement. Conclusion: In this study, a PSA decline of > 50% proved significantly associated with OS and PFS in multivariate analysis following treatment with 225Ac-PSMA-617. Furthermore, previous 177Lu-PSMA treatment was negatively associated with PFS in both uni- and multivariate analysis.

  • Radionuclide Therapy
  • Actinium-225
  • PSA response
  • PSMA
  • prostate carcinoma
  • radioligand therapy
  • Copyright © 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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Journal of Nuclear Medicine: 62 (3)
Journal of Nuclear Medicine
Vol. 62, Issue 3
March 1, 2021
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PREDICTORS OF OVERALL AND DISEASE FREE SURVIVAL IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER PATIENTS RECEIVING 225Ac-PSMA-617 RADIOLIGAND THERAPY
Mike Sathekge, Frank Bruchertseifer, Mariza Vorster, Ismaheel Lawal, Otto Knoesen, Johncy Mahapane, Cindy Davis, Florette Reyneke, Alex Maes, Clemens Kratochwil, Thabo Lengana, Frederik Giesel, Christophe Van de Wiele, Alfred Morgenstern
Journal of Nuclear Medicine May 2019, jnumed.119.229229; DOI: 10.2967/jnumed.119.229229

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PREDICTORS OF OVERALL AND DISEASE FREE SURVIVAL IN METASTATIC CASTRATION-RESISTANT PROSTATE CANCER PATIENTS RECEIVING 225Ac-PSMA-617 RADIOLIGAND THERAPY
Mike Sathekge, Frank Bruchertseifer, Mariza Vorster, Ismaheel Lawal, Otto Knoesen, Johncy Mahapane, Cindy Davis, Florette Reyneke, Alex Maes, Clemens Kratochwil, Thabo Lengana, Frederik Giesel, Christophe Van de Wiele, Alfred Morgenstern
Journal of Nuclear Medicine May 2019, jnumed.119.229229; DOI: 10.2967/jnumed.119.229229
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Keywords

  • Radionuclide Therapy
  • actinium-225
  • PSA response
  • PSMA
  • prostate carcinoma
  • radioligand therapy
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