Intermittent Radioligand Therapy with <sup>177</sup>Lu-PSMA-617 for Oligometastatic Castration-Resistant Prostate Cancer
<sup>177</sup>Lu-PSMA-617 radioligand therapy (<sup>177</sup>Lu-PSMA-RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC) currently consists of 4–6 cycles of 6.0–7.4 GBq of <sup>177</sup>Lu-PSMA-617 each every 6–8 weeks. While safety and e...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/18/4605 |
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| author | Nicolai Mader Christina Schoeler Niloufar Pezeshkpour Konrad Klimek Daniel Groener Christian Happel Nikolaos Tselis Philipp Mandel Frank Grünwald Amir Sabet |
| author_facet | Nicolai Mader Christina Schoeler Niloufar Pezeshkpour Konrad Klimek Daniel Groener Christian Happel Nikolaos Tselis Philipp Mandel Frank Grünwald Amir Sabet |
| author_sort | Nicolai Mader |
| collection | DOAJ |
| description | <sup>177</sup>Lu-PSMA-617 radioligand therapy (<sup>177</sup>Lu-PSMA-RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC) currently consists of 4–6 cycles of 6.0–7.4 GBq of <sup>177</sup>Lu-PSMA-617 each every 6–8 weeks. While safety and efficacy could be demonstrated in larger prospective trials irrespective of the tumor burden at <sup>177</sup>Lu-PSMA RLT initiation, increased renal absorbed doses due to a reduced tumor sink effect in early responding, oligometastatic mCRPC patients pose difficulties. Response-adapted, dose distributing, intermittent treatment with up to six cycles has not been routinely performed, due to concerns about the potential loss of disease control. Treatment was discontinued in 19 early-responding patients with oligometastatic tumor burden after two (IQR 2–3) cycles of <sup>177</sup>Lu-PSMA-RLT and 6.5 ± 0.7 GBq per cycle and resumed upon <sup>68</sup>Ga-PSMA-11-PET/CT-based progression (according to the PCWG3 criteria). Subsequent treatment breaks were imposed if a PSMA-based imaging response could be achieved. A total of five (IQR 3–6) cycles reaching a cumulative activity of 32 ± 11 GBq were applied. A routine blood work-up including blood counts and liver and renal function was measured throughout the <sup>177</sup>Lu-PSMA-RLT and follow-up to grade toxicity according to CTCAE v5.0 criteria. Survival outcome was calculated based on the Kaplan–Meier method. In total, treatment-free periods of 9 (IQR 6–17) cumulative months and the application of <sup>177</sup>Lu-PSMA-RLT cycles over 16 (IQR 9–22) months could be achieved. Fifteen (84%) patients responded to subsequent cycles after the first treatment break and in 7/19 (37%) patients, intermittent <sup>177</sup>Lu-PSMA-RLT consisted of ≥2 treatment breaks. The median PFS was 27 months (95% CI: 23–31) and overall survival was 45 months (95% CI: 28–62). No grade ≥3 hematological or renal toxicities could be observed during the 45 ± 21 months of follow-up. The cumulative mean renal absorbed dose was 16.7 ± 8.3 Gy and 0.53 ± 0.21 Gy/GBq. Intermittent radioligand therapy with <sup>177</sup>Lu-PSMA-617 is feasible in early-responding patients with oligometastatic disease. A late onset of progression after subsequent cycles and the absence of significant toxicity warrants further investigation of the concept of intermittent treatment in selected patients. |
| first_indexed | 2024-03-10T22:57:49Z |
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| last_indexed | 2024-03-10T22:57:49Z |
| publishDate | 2023-09-01 |
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| spelling | doaj.art-f6e2c32503ce4d9a9e273c2ca5b79aab2023-11-19T09:56:09ZengMDPI AGCancers2072-66942023-09-011518460510.3390/cancers15184605Intermittent Radioligand Therapy with <sup>177</sup>Lu-PSMA-617 for Oligometastatic Castration-Resistant Prostate CancerNicolai Mader0Christina Schoeler1Niloufar Pezeshkpour2Konrad Klimek3Daniel Groener4Christian Happel5Nikolaos Tselis6Philipp Mandel7Frank Grünwald8Amir Sabet9Department of Nuclear Medicine, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Nuclear Medicine, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Nuclear Medicine, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Nuclear Medicine, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Nuclear Medicine, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Nuclear Medicine, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Radiation Oncology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Urology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Nuclear Medicine, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Nuclear Medicine, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany<sup>177</sup>Lu-PSMA-617 radioligand therapy (<sup>177</sup>Lu-PSMA-RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC) currently consists of 4–6 cycles of 6.0–7.4 GBq of <sup>177</sup>Lu-PSMA-617 each every 6–8 weeks. While safety and efficacy could be demonstrated in larger prospective trials irrespective of the tumor burden at <sup>177</sup>Lu-PSMA RLT initiation, increased renal absorbed doses due to a reduced tumor sink effect in early responding, oligometastatic mCRPC patients pose difficulties. Response-adapted, dose distributing, intermittent treatment with up to six cycles has not been routinely performed, due to concerns about the potential loss of disease control. Treatment was discontinued in 19 early-responding patients with oligometastatic tumor burden after two (IQR 2–3) cycles of <sup>177</sup>Lu-PSMA-RLT and 6.5 ± 0.7 GBq per cycle and resumed upon <sup>68</sup>Ga-PSMA-11-PET/CT-based progression (according to the PCWG3 criteria). Subsequent treatment breaks were imposed if a PSMA-based imaging response could be achieved. A total of five (IQR 3–6) cycles reaching a cumulative activity of 32 ± 11 GBq were applied. A routine blood work-up including blood counts and liver and renal function was measured throughout the <sup>177</sup>Lu-PSMA-RLT and follow-up to grade toxicity according to CTCAE v5.0 criteria. Survival outcome was calculated based on the Kaplan–Meier method. In total, treatment-free periods of 9 (IQR 6–17) cumulative months and the application of <sup>177</sup>Lu-PSMA-RLT cycles over 16 (IQR 9–22) months could be achieved. Fifteen (84%) patients responded to subsequent cycles after the first treatment break and in 7/19 (37%) patients, intermittent <sup>177</sup>Lu-PSMA-RLT consisted of ≥2 treatment breaks. The median PFS was 27 months (95% CI: 23–31) and overall survival was 45 months (95% CI: 28–62). No grade ≥3 hematological or renal toxicities could be observed during the 45 ± 21 months of follow-up. The cumulative mean renal absorbed dose was 16.7 ± 8.3 Gy and 0.53 ± 0.21 Gy/GBq. Intermittent radioligand therapy with <sup>177</sup>Lu-PSMA-617 is feasible in early-responding patients with oligometastatic disease. A late onset of progression after subsequent cycles and the absence of significant toxicity warrants further investigation of the concept of intermittent treatment in selected patients.https://www.mdpi.com/2072-6694/15/18/4605prostate-specific membrane antigen (PSMA)<sup>177</sup>Lu-PSMA-617radioligand therapy (RLT)intermittent treatmentmetastatic castration-resistant prostate cancer (mCRPC) |
| spellingShingle | Nicolai Mader Christina Schoeler Niloufar Pezeshkpour Konrad Klimek Daniel Groener Christian Happel Nikolaos Tselis Philipp Mandel Frank Grünwald Amir Sabet Intermittent Radioligand Therapy with <sup>177</sup>Lu-PSMA-617 for Oligometastatic Castration-Resistant Prostate Cancer Cancers prostate-specific membrane antigen (PSMA) <sup>177</sup>Lu-PSMA-617 radioligand therapy (RLT) intermittent treatment metastatic castration-resistant prostate cancer (mCRPC) |
| title | Intermittent Radioligand Therapy with <sup>177</sup>Lu-PSMA-617 for Oligometastatic Castration-Resistant Prostate Cancer |
| title_full | Intermittent Radioligand Therapy with <sup>177</sup>Lu-PSMA-617 for Oligometastatic Castration-Resistant Prostate Cancer |
| title_fullStr | Intermittent Radioligand Therapy with <sup>177</sup>Lu-PSMA-617 for Oligometastatic Castration-Resistant Prostate Cancer |
| title_full_unstemmed | Intermittent Radioligand Therapy with <sup>177</sup>Lu-PSMA-617 for Oligometastatic Castration-Resistant Prostate Cancer |
| title_short | Intermittent Radioligand Therapy with <sup>177</sup>Lu-PSMA-617 for Oligometastatic Castration-Resistant Prostate Cancer |
| title_sort | intermittent radioligand therapy with sup 177 sup lu psma 617 for oligometastatic castration resistant prostate cancer |
| topic | prostate-specific membrane antigen (PSMA) <sup>177</sup>Lu-PSMA-617 radioligand therapy (RLT) intermittent treatment metastatic castration-resistant prostate cancer (mCRPC) |
| url | https://www.mdpi.com/2072-6694/15/18/4605 |
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