Renal Safety of [<sup>177</sup>Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Compromised Baseline Kidney Function
<i>Background:</i> Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is an effective antitumor-treatment in metastatic castration-resistant prostate carcinoma (mCRPC). Concerns of potential nephrotoxicity are based on renal tubular PSMA expression and the resu...
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MDPI AG
2021-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/12/3095 |
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| author | Florian Rosar Niklas Kochems Mark Bartholomä Stephan Maus Tobias Stemler Johannes Linxweiler Fadi Khreish Samer Ezziddin |
| author_facet | Florian Rosar Niklas Kochems Mark Bartholomä Stephan Maus Tobias Stemler Johannes Linxweiler Fadi Khreish Samer Ezziddin |
| author_sort | Florian Rosar |
| collection | DOAJ |
| description | <i>Background:</i> Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is an effective antitumor-treatment in metastatic castration-resistant prostate carcinoma (mCRPC). Concerns of potential nephrotoxicity are based on renal tubular PSMA expression and the resulting radiopharmaceutical retention during RLT, but data confirming clinically significant renal toxicity are still lacking. In this study, patients with significantly impaired baseline kidney function before initiation of therapy were investigated for treatment-associated nephrotoxicity and the potential relationship with administered activities of [<sup>177</sup>Lu]Lu-PSMA-617. <i>Methods:</i> Twenty-two mCRPC patients with impaired renal function (glomerular filtration rate (GFR) ≤ 60 mL/min) who received more than two cycles of [<sup>177</sup>Lu]Lu-PSMA-617 RLT (median 5 cycles and median 6-week time interval between consecutive cycles) were analyzed in this study. Patients were treated within a prospective patient registry (REALITY Study, NCT04833517). Cumulative administered activities ranged from 17.1 to 85.6 GBq with a median activity of 6.5 GBq per cycle. Renal function was closely monitored during and after PSMA-RLT. <i>Results:</i> Mean pre-treatment GFR was 45.0 ± 10.7 mL/min. After two (22/22 patients), four (20/22 patients), and six cycles (10/22 patients) of RLT, a significant increase of GFR was noted (each <i>p</i> < 0.05). End-of-treatment GFR (54.1 ± 16.7 mL/min) was significantly higher than baseline GFR (<i>p</i> = 0.016). Only one patient experienced deterioration of renal function (change of CTCAE grade 2 to 3). The remaining patients showed no significant reduction of GFR, including follow-up assessments (6, 9, and 12 months), and even showed improved (10/22 patients) or unchanged (11/22 patients) CTCAE-based renal impairment grades during and after the end of PSMA-RLT. No significant correlation between the change in GFR and per-cycle (<i>p</i> = 0.605) or cumulative (<i>p</i> = 0.132) administered activities were found. <i>Conclusions:</i> As pre-treatment chronic kidney failure did not lead to detectable RLT-induced deterioration of renal function in our study, the nephrotoxic potential of [<sup>177</sup>Lu]Lu-PSMA-617 RLT may be overestimated and not of clinical priority in the setting of palliative treatment in mCRPC. We suggest not to categorically exclude patients from enrolment to PSMA-RLT due to renal impairment. |
| first_indexed | 2024-03-10T10:13:03Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
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| last_indexed | 2024-03-10T10:13:03Z |
| publishDate | 2021-06-01 |
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| spelling | doaj.art-d58abd2a9c3146aa9ca659b2ca1dda772023-11-22T01:02:33ZengMDPI AGCancers2072-66942021-06-011312309510.3390/cancers13123095Renal Safety of [<sup>177</sup>Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Compromised Baseline Kidney FunctionFlorian Rosar0Niklas Kochems1Mark Bartholomä2Stephan Maus3Tobias Stemler4Johannes Linxweiler5Fadi Khreish6Samer Ezziddin7Department of Nuclear Medicine, Saarland University, 66421 Homburg, GermanyDepartment of Nuclear Medicine, Saarland University, 66421 Homburg, GermanyDepartment of Nuclear Medicine, Saarland University, 66421 Homburg, GermanyDepartment of Nuclear Medicine, Saarland University, 66421 Homburg, GermanyDepartment of Nuclear Medicine, Saarland University, 66421 Homburg, GermanyDepartment of Urology, Saarland University, 66421 Homburg, GermanyDepartment of Nuclear Medicine, Saarland University, 66421 Homburg, GermanyDepartment of Nuclear Medicine, Saarland University, 66421 Homburg, Germany<i>Background:</i> Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is an effective antitumor-treatment in metastatic castration-resistant prostate carcinoma (mCRPC). Concerns of potential nephrotoxicity are based on renal tubular PSMA expression and the resulting radiopharmaceutical retention during RLT, but data confirming clinically significant renal toxicity are still lacking. In this study, patients with significantly impaired baseline kidney function before initiation of therapy were investigated for treatment-associated nephrotoxicity and the potential relationship with administered activities of [<sup>177</sup>Lu]Lu-PSMA-617. <i>Methods:</i> Twenty-two mCRPC patients with impaired renal function (glomerular filtration rate (GFR) ≤ 60 mL/min) who received more than two cycles of [<sup>177</sup>Lu]Lu-PSMA-617 RLT (median 5 cycles and median 6-week time interval between consecutive cycles) were analyzed in this study. Patients were treated within a prospective patient registry (REALITY Study, NCT04833517). Cumulative administered activities ranged from 17.1 to 85.6 GBq with a median activity of 6.5 GBq per cycle. Renal function was closely monitored during and after PSMA-RLT. <i>Results:</i> Mean pre-treatment GFR was 45.0 ± 10.7 mL/min. After two (22/22 patients), four (20/22 patients), and six cycles (10/22 patients) of RLT, a significant increase of GFR was noted (each <i>p</i> < 0.05). End-of-treatment GFR (54.1 ± 16.7 mL/min) was significantly higher than baseline GFR (<i>p</i> = 0.016). Only one patient experienced deterioration of renal function (change of CTCAE grade 2 to 3). The remaining patients showed no significant reduction of GFR, including follow-up assessments (6, 9, and 12 months), and even showed improved (10/22 patients) or unchanged (11/22 patients) CTCAE-based renal impairment grades during and after the end of PSMA-RLT. No significant correlation between the change in GFR and per-cycle (<i>p</i> = 0.605) or cumulative (<i>p</i> = 0.132) administered activities were found. <i>Conclusions:</i> As pre-treatment chronic kidney failure did not lead to detectable RLT-induced deterioration of renal function in our study, the nephrotoxic potential of [<sup>177</sup>Lu]Lu-PSMA-617 RLT may be overestimated and not of clinical priority in the setting of palliative treatment in mCRPC. We suggest not to categorically exclude patients from enrolment to PSMA-RLT due to renal impairment.https://www.mdpi.com/2072-6694/13/12/3095PSMA radioligand therapy<sup>177</sup>Lusafetykidneyrenal functionmetastatic castration-resistant prostate carcinoma |
| spellingShingle | Florian Rosar Niklas Kochems Mark Bartholomä Stephan Maus Tobias Stemler Johannes Linxweiler Fadi Khreish Samer Ezziddin Renal Safety of [<sup>177</sup>Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Compromised Baseline Kidney Function Cancers PSMA radioligand therapy <sup>177</sup>Lu safety kidney renal function metastatic castration-resistant prostate carcinoma |
| title | Renal Safety of [<sup>177</sup>Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Compromised Baseline Kidney Function |
| title_full | Renal Safety of [<sup>177</sup>Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Compromised Baseline Kidney Function |
| title_fullStr | Renal Safety of [<sup>177</sup>Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Compromised Baseline Kidney Function |
| title_full_unstemmed | Renal Safety of [<sup>177</sup>Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Compromised Baseline Kidney Function |
| title_short | Renal Safety of [<sup>177</sup>Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Compromised Baseline Kidney Function |
| title_sort | renal safety of sup 177 sup lu lu psma 617 radioligand therapy in patients with compromised baseline kidney function |
| topic | PSMA radioligand therapy <sup>177</sup>Lu safety kidney renal function metastatic castration-resistant prostate carcinoma |
| url | https://www.mdpi.com/2072-6694/13/12/3095 |
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