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Outcome of (177)Lu-PSMA-617 Radioligand Therapy in Chemo-Refractory Patients with Metastatic Castration-Resistant Early-Onset Prostate Cancer

SIMPLE SUMMARY: The risk of prostate cancer development, the second most commonly occurring cancer in men overall, increases strongly with age. About 10% of patients, however, are diagnosed with early-onset prostate cancer (age at diagnosis: ≤55 years). This is considered to be a distinct clinical a...

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Autores principales: Mader, Nicolai, Groener, Daniel, Tselis, Nikolaos, Banek, Séverine, Nagarajah, James, Grünwald, Frank, Sabet, Amir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392017/
https://www.ncbi.nlm.nih.gov/pubmed/34439347
http://dx.doi.org/10.3390/cancers13164193
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author Mader, Nicolai
Groener, Daniel
Tselis, Nikolaos
Banek, Séverine
Nagarajah, James
Grünwald, Frank
Sabet, Amir
author_facet Mader, Nicolai
Groener, Daniel
Tselis, Nikolaos
Banek, Séverine
Nagarajah, James
Grünwald, Frank
Sabet, Amir
author_sort Mader, Nicolai
collection PubMed
description SIMPLE SUMMARY: The risk of prostate cancer development, the second most commonly occurring cancer in men overall, increases strongly with age. About 10% of patients, however, are diagnosed with early-onset prostate cancer (age at diagnosis: ≤55 years). This is considered to be a distinct clinical and pathological phenotype with a poor prognosis. Generally, prostate cancer cells express high quantities of prostate-specific membrane antigen (PSMA) on their surface. Radioligand therapy is a type of treatment, which, among other available agents, uses the beta-emitting radionuclide (177)Lutetium ((177)Lu) and a PSMA-targeting ligand termed PSMA-617 for internal irradiation of metastatic prostate cancer cells. The aim of our retrospective study was to assess the efficacy and safety of radioligand therapy with (177)Lu-PSMA-617 in early-onset metastasized castration-resistant prostate cancer patients refractory to chemotherapy. Special emphasis was placed on the patients’ response to the treatment and survival. The study provides support for the expected shorter survival compared to heterogenous patient groups. ABSTRACT: The aim of this retrospective study was to assess the outcome of patients with metastasized castration-resistant early-onset prostate cancer refractory to chemotherapy receiving radioligand therapy with (177)Lutetium-PSMA-617 (LuPSMA-RLT). Twenty-five patients of ≤55 years of age at prostate cancer diagnosis, treated with a median of four (IQR 2–6) cycles (mean of 7.7 ± 1.4 GBq per cycle) every 6–8 weeks, were analyzed. Survival outcome was calculated based on the Kaplan–Meier method. The median progression-free survival (PFS) was 3.8 months (95% CI 2.3–5.3), and overall survival (OS) was 8.5 months (95% CI 6.2–10.8). An initial PSA reduction (≥ 50%) was observed in 9/25 (36%) of patients without being significantly associated with OS (p = 0.601). PSA response (PSA decline ≥50% at 12 weeks) was observed in 12/25 (48%) of patients and significantly associated with longer OS (16.0 months, 95% CI 7.4–24.6 vs. 4.0 months, 95% CI 1.1–6.9, p = 0.002). Imaging-based response using (68)Ga-PSMA-11-PET/CT after two to three cycles was seen in 11/25 (44%). Additionally, responders had a significantly longer median PFS (8.7 months, 95% CI 1.3–16.1 vs. 1.9 months, 95% CI 1.7–2.2, p < 0.001) and OS (16.0 months, 95% CI 7.6–24.4 vs. 4.0 months, 95% CI 0.9–7.1; p = 0.002). Intra- or post-therapeutic toxicity was graded according to the CTCAE v5.0 criteria. Newly developing grade ≥ 3 anemia, leukopenia, and thrombocytopenia occurred in three (12%), one (4%), and three (12%) patients, respectively. One patient showed renal toxicity (grade ≥ 3) during follow-up. Pain palliation (>2 level VAS decline) was achieved in 9/14 (64%) and performance status improvement (ECOG level decline ≥ 1) in 8/17 (47%) of patients. Compared to previous reports, radioligand therapy with (177)Lu-PSMA-617 in metastasized castration-resistant early-onset prostate cancer patients refractory to chemotherapy yields similar response rates with a comparable safety profile, but is associated with shorter survival.
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spelling pubmed-83920172021-08-28 Outcome of (177)Lu-PSMA-617 Radioligand Therapy in Chemo-Refractory Patients with Metastatic Castration-Resistant Early-Onset Prostate Cancer Mader, Nicolai Groener, Daniel Tselis, Nikolaos Banek, Séverine Nagarajah, James Grünwald, Frank Sabet, Amir Cancers (Basel) Article SIMPLE SUMMARY: The risk of prostate cancer development, the second most commonly occurring cancer in men overall, increases strongly with age. About 10% of patients, however, are diagnosed with early-onset prostate cancer (age at diagnosis: ≤55 years). This is considered to be a distinct clinical and pathological phenotype with a poor prognosis. Generally, prostate cancer cells express high quantities of prostate-specific membrane antigen (PSMA) on their surface. Radioligand therapy is a type of treatment, which, among other available agents, uses the beta-emitting radionuclide (177)Lutetium ((177)Lu) and a PSMA-targeting ligand termed PSMA-617 for internal irradiation of metastatic prostate cancer cells. The aim of our retrospective study was to assess the efficacy and safety of radioligand therapy with (177)Lu-PSMA-617 in early-onset metastasized castration-resistant prostate cancer patients refractory to chemotherapy. Special emphasis was placed on the patients’ response to the treatment and survival. The study provides support for the expected shorter survival compared to heterogenous patient groups. ABSTRACT: The aim of this retrospective study was to assess the outcome of patients with metastasized castration-resistant early-onset prostate cancer refractory to chemotherapy receiving radioligand therapy with (177)Lutetium-PSMA-617 (LuPSMA-RLT). Twenty-five patients of ≤55 years of age at prostate cancer diagnosis, treated with a median of four (IQR 2–6) cycles (mean of 7.7 ± 1.4 GBq per cycle) every 6–8 weeks, were analyzed. Survival outcome was calculated based on the Kaplan–Meier method. The median progression-free survival (PFS) was 3.8 months (95% CI 2.3–5.3), and overall survival (OS) was 8.5 months (95% CI 6.2–10.8). An initial PSA reduction (≥ 50%) was observed in 9/25 (36%) of patients without being significantly associated with OS (p = 0.601). PSA response (PSA decline ≥50% at 12 weeks) was observed in 12/25 (48%) of patients and significantly associated with longer OS (16.0 months, 95% CI 7.4–24.6 vs. 4.0 months, 95% CI 1.1–6.9, p = 0.002). Imaging-based response using (68)Ga-PSMA-11-PET/CT after two to three cycles was seen in 11/25 (44%). Additionally, responders had a significantly longer median PFS (8.7 months, 95% CI 1.3–16.1 vs. 1.9 months, 95% CI 1.7–2.2, p < 0.001) and OS (16.0 months, 95% CI 7.6–24.4 vs. 4.0 months, 95% CI 0.9–7.1; p = 0.002). Intra- or post-therapeutic toxicity was graded according to the CTCAE v5.0 criteria. Newly developing grade ≥ 3 anemia, leukopenia, and thrombocytopenia occurred in three (12%), one (4%), and three (12%) patients, respectively. One patient showed renal toxicity (grade ≥ 3) during follow-up. Pain palliation (>2 level VAS decline) was achieved in 9/14 (64%) and performance status improvement (ECOG level decline ≥ 1) in 8/17 (47%) of patients. Compared to previous reports, radioligand therapy with (177)Lu-PSMA-617 in metastasized castration-resistant early-onset prostate cancer patients refractory to chemotherapy yields similar response rates with a comparable safety profile, but is associated with shorter survival. MDPI 2021-08-20 /pmc/articles/PMC8392017/ /pubmed/34439347 http://dx.doi.org/10.3390/cancers13164193 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mader, Nicolai
Groener, Daniel
Tselis, Nikolaos
Banek, Séverine
Nagarajah, James
Grünwald, Frank
Sabet, Amir
Outcome of (177)Lu-PSMA-617 Radioligand Therapy in Chemo-Refractory Patients with Metastatic Castration-Resistant Early-Onset Prostate Cancer
title Outcome of (177)Lu-PSMA-617 Radioligand Therapy in Chemo-Refractory Patients with Metastatic Castration-Resistant Early-Onset Prostate Cancer
title_full Outcome of (177)Lu-PSMA-617 Radioligand Therapy in Chemo-Refractory Patients with Metastatic Castration-Resistant Early-Onset Prostate Cancer
title_fullStr Outcome of (177)Lu-PSMA-617 Radioligand Therapy in Chemo-Refractory Patients with Metastatic Castration-Resistant Early-Onset Prostate Cancer
title_full_unstemmed Outcome of (177)Lu-PSMA-617 Radioligand Therapy in Chemo-Refractory Patients with Metastatic Castration-Resistant Early-Onset Prostate Cancer
title_short Outcome of (177)Lu-PSMA-617 Radioligand Therapy in Chemo-Refractory Patients with Metastatic Castration-Resistant Early-Onset Prostate Cancer
title_sort outcome of (177)lu-psma-617 radioligand therapy in chemo-refractory patients with metastatic castration-resistant early-onset prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392017/
https://www.ncbi.nlm.nih.gov/pubmed/34439347
http://dx.doi.org/10.3390/cancers13164193
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