The impact of repeated cycles of radioligand therapy using [177Lu]Lu-PSMA-617 on renal function in patients with hormone refractory metastatic prostate cancer.
BACKGROUND
[177Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring.


METHODS
Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [177Lu]Lu-PSMA-617 were investigated. Renal function was assessed through laboratory tests (creatinine, GFR, cystatin C) and Tc-99 m-MAG3 measurements. Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. To identify risk factors for renal toxicity, we used Pearson's correlation coefficient and the corresponding p values.


RESULTS
None of the 55 patients experienced severe nephrotoxicity (grade 3/4). In 14 patients (25%), we observed increased creatinine levels of CTC 1° or 2°. There were 16 cases of increased GFR (grade 1/2). At the baseline, only 14 patients had elevated cystatin C. However, post-therapeutic cystatin C was elevated in 32 patients (58%). A significant effect on renal function was found for age (p = 0.049), hypertension (p = 0.001) and pre-existing kidney disease (p = 0.001). The most reliable predictive markers of nephrotoxicity were TER-MAG3 and cystatin C.


CONCLUSIONS
Renal toxicity in patients treated with [177Lu]Lu-PSMA-617 was low. There was no (sub)acute grade 3 or 4 nephrotoxicity.
Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Anna
A
Yordanova
Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Anja
A
Becker
Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Elisabeth
E
Eppard
Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Stefan
S
Kürpig
Department of Urology, University Hospital Bonn, Bonn, Germany.
Christian
C
Fisang
Department of Internal Medicine, MED3, University Hospital Bonn, Bonn, Germany.
Georg
G
Feldmann
Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Markus
M
Essler
Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. hojjat.ahmadzadehfar@ukbonn.de.
Hojjat
H
Ahmadzadehfar
D000368:Aged; D004151:Dipeptides / Q000009:adverse effects* / Q000627:therapeutic use; D006573:Heterocyclic Compounds, 1-Ring / Q000009:adverse effects* / Q000627:therapeutic use; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000503:physiopathology* / Q000528:radiation effects*; D008024:Ligands; D008187:Lutetium / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000532:radiotherapy*; D011868:Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure
D004151:Dipeptides; D006573:Heterocyclic Compounds, 1-Ring; D006728:Hormones; D008024:Ligands; C000602389:PSMA-617; D011868:Radioisotopes; D008187:Lutetium; C000615061:Lutetium-177; D017430:Prostate-Specific Antigen
177Lu; Nephrotoxicity; PSMA; Prostate cancer; Radioligand therapy; Renal function