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Overall Survival with [<sup>177</sup>Lu]Lu-PSMA-617 Versus [<sup>177</sup>Lu]Lu-PSMA I&T: A Propensity Score-Matched Real-World Analysis.

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Long-Term Nephrotoxicity of 177Lu-PSMA Radioligand Therapy.

Lisa Steinhelfer1,2, Lukas Lunger3, Lisena Cala1

  • 1Department of Nuclear Medicine, School of Medicine, and Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
|October 19, 2023
PubMed
Summary

Lutetium-177 PSMA (177Lu-PSMA) therapy for prostate cancer can lead to significant kidney function decline in nearly half of patients within a year. Pre-existing risk factors worsen this nephrotoxicity, highlighting the need for further research.

Keywords:
PSMAlutetiummCRPCnephrotoxicityradioligand therapy

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Area of Science:

  • Nuclear Medicine
  • Oncology
  • Nephrology

Background:

  • Prostate-specific membrane antigen (PSMA) targeted radioligand therapy with beta-emitting 177Lu is an established treatment for metastatic castration-resistant prostate cancer.
  • Long-term data regarding the nephrotoxicity of 177Lu-PSMA therapy are limited, necessitating further investigation into its renal effects.

Purpose of the Study:

  • To retrospectively assess the estimated glomerular filtration rate (eGFR) dynamics for at least 12 months post-177Lu-PSMA treatment in a cohort of patients with metastatic castration-resistant prostate cancer.
  • To identify factors associated with changes in renal function following 177Lu-PSMA therapy.

Main Methods:

  • Retrospective analysis of 106 patients from 3 German centers who received at least 4 cycles of 177Lu-PSMA and had 12-month eGFR follow-up.
  • eGFR was calculated using the CKD-EPI formula and analyzed using monoexponentially fitted curves at 3, 6, and 12 months post-therapy.
  • Multivariable linear regression analyzed associations between eGFR changes and baseline risk factors, prior treatments, and treatment cycles.

Main Results:

  • 45% of patients experienced at least moderate eGFR decrease (≥15%) one year after 177Lu-PSMA therapy.
  • Nearly half of those with moderate decreases (23/48) showed severe (≥30%) or very severe (≥40%) eGFR reduction.
  • A higher number of baseline risk factors was significantly associated with greater eGFR decline (-4.51, P=0.03).

Conclusions:

  • A substantial proportion of patients undergoing 177Lu-PSMA therapy for prostate cancer may experience significant kidney function impairment one year post-treatment.
  • Baseline nephrotoxic risk factors appear to exacerbate the loss of renal function.
  • Prospective studies are essential to accurately determine the long-term nephrotoxic potential of 177Lu-PSMA therapy.