Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases
The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has substantially evolved over the last decade. Nonetheless, a better understanding of bone-targeted agents (BTAs) action in mCRPC remains an unmet need. Theuse of BTAs aims to reduce the incidence of skeletal-relat...
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MDPI AG
2020-07-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/8/2034 |
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| author | Soraia Lobo-Martins Arlindo R. Ferreira André Mansinho Sandra Casimiro Kim Leitzel Suhail Ali Allan Lipton Luís Costa |
| author_facet | Soraia Lobo-Martins Arlindo R. Ferreira André Mansinho Sandra Casimiro Kim Leitzel Suhail Ali Allan Lipton Luís Costa |
| author_sort | Soraia Lobo-Martins |
| collection | DOAJ |
| description | The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has substantially evolved over the last decade. Nonetheless, a better understanding of bone-targeted agents (BTAs) action in mCRPC remains an unmet need. Theuse of BTAs aims to reduce the incidence of skeletal-related events (SREs) in patients with mCRPC. Less frequent BTA schedules are currently being studied to minimize adverse events. In this study, the impact of metastatic compartment (bone and extraskeletal metastases (BESM) vs. bone-only metastases (BOM)) on bone biomarker kinetics, time to first on-study SRE, and symptomatic skeletal events (SSEs) is evaluated. This is a retrospective analysis of the prospective, randomized, multicenter clinical trial of denosumab vs. zoledronic acid in patients with mCRPC and bone metastases. A total of 1901 patients were included, 1559 (82.0%) with BOM and 342 with BESM (18.0%). Bone metastases burden was balanced between groups. Baseline levels and normalization rates of corrected urinary N-terminal telopeptide and bone alkaline phosphatase did not differ between groups. However, BESM patients had a higher risk of SREs (adjusted HR 1.21; 95% CI 1.01–1.46; <i>p</i> = 0.043) and SSEs (adjusted HR 1.30; 95% CI 1.06–1.61; <i>p</i> = 0.014). This difference was more pronounced in the first 12 months of BTA treatment.In mCRPC, strategies of BTA schedule de-escalation may take into account presence of extraskeletal metastases. |
| first_indexed | 2024-03-10T18:14:24Z |
| format | Article |
| id | doaj.art-c7dac0bd31d3404c98402af86e54b4b3 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:14:24Z |
| publishDate | 2020-07-01 |
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| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c7dac0bd31d3404c98402af86e54b4b32023-11-20T07:49:47ZengMDPI AGCancers2072-66942020-07-01128203410.3390/cancers12082034Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone MetastasesSoraia Lobo-Martins0Arlindo R. Ferreira1André Mansinho2Sandra Casimiro3Kim Leitzel4Suhail Ali5Allan Lipton6Luís Costa7Oncology Division, Hospital de Santa Maria, 1649-035 Lisbon, PortugalInstituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, PortugalOncology Division, Hospital de Santa Maria, 1649-035 Lisbon, PortugalInstituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, PortugalDivision of Hematology/Oncology, Penn State Health Milton S Hershey Medical Center, Hershey, PA17033, USADivision of Hematology/Oncology, Penn State Health Milton S Hershey Medical Center, Hershey, PA17033, USADivision of Hematology/Oncology, Penn State Health Milton S Hershey Medical Center, Hershey, PA17033, USAOncology Division, Hospital de Santa Maria, 1649-035 Lisbon, PortugalThe therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has substantially evolved over the last decade. Nonetheless, a better understanding of bone-targeted agents (BTAs) action in mCRPC remains an unmet need. Theuse of BTAs aims to reduce the incidence of skeletal-related events (SREs) in patients with mCRPC. Less frequent BTA schedules are currently being studied to minimize adverse events. In this study, the impact of metastatic compartment (bone and extraskeletal metastases (BESM) vs. bone-only metastases (BOM)) on bone biomarker kinetics, time to first on-study SRE, and symptomatic skeletal events (SSEs) is evaluated. This is a retrospective analysis of the prospective, randomized, multicenter clinical trial of denosumab vs. zoledronic acid in patients with mCRPC and bone metastases. A total of 1901 patients were included, 1559 (82.0%) with BOM and 342 with BESM (18.0%). Bone metastases burden was balanced between groups. Baseline levels and normalization rates of corrected urinary N-terminal telopeptide and bone alkaline phosphatase did not differ between groups. However, BESM patients had a higher risk of SREs (adjusted HR 1.21; 95% CI 1.01–1.46; <i>p</i> = 0.043) and SSEs (adjusted HR 1.30; 95% CI 1.06–1.61; <i>p</i> = 0.014). This difference was more pronounced in the first 12 months of BTA treatment.In mCRPC, strategies of BTA schedule de-escalation may take into account presence of extraskeletal metastases.https://www.mdpi.com/2072-6694/12/8/2034prostate cancermetastatic castration-resistant prostate cancerbone-targeted agentsbone metastasesvisceral metastases |
| spellingShingle | Soraia Lobo-Martins Arlindo R. Ferreira André Mansinho Sandra Casimiro Kim Leitzel Suhail Ali Allan Lipton Luís Costa Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases Cancers prostate cancer metastatic castration-resistant prostate cancer bone-targeted agents bone metastases visceral metastases |
| title | Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases |
| title_full | Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases |
| title_fullStr | Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases |
| title_full_unstemmed | Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases |
| title_short | Impact of Extraskeletal Metastases on Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer with Bone Metastases |
| title_sort | impact of extraskeletal metastases on skeletal related events in metastatic castration resistant prostate cancer with bone metastases |
| topic | prostate cancer metastatic castration-resistant prostate cancer bone-targeted agents bone metastases visceral metastases |
| url | https://www.mdpi.com/2072-6694/12/8/2034 |
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