Low Blood Levels of LRG1 Before Radical Prostatectomy Identify Patients with High Risk of Progression to Castration-resistant Prostate Cancer
Background: After radical prostatectomy (RP), depending on stage, up to 40% of patients with prostate cancer (PCa) will experience biochemical failure (BF). Despite salvage therapy, approximately one-third of these patients will need permanent hormone therapy (pHT) and are at risk of progression to...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | European Urology Open Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666168322019000 |
| _version_ | 1798046313148841984 |
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| author | Ingrid Jenny Guldvik Peder Rustøen Braadland Shivanthe Sivanesan Håkon Ramberg Gitte Kristensen Pierre Tennstedt Andreas Røder Thorsten Schlomm Viktor Berge Lars Magne Eri Wolfgang Lilleby Ian G. Mills Kristin Austlid Taskén |
| author_facet | Ingrid Jenny Guldvik Peder Rustøen Braadland Shivanthe Sivanesan Håkon Ramberg Gitte Kristensen Pierre Tennstedt Andreas Røder Thorsten Schlomm Viktor Berge Lars Magne Eri Wolfgang Lilleby Ian G. Mills Kristin Austlid Taskén |
| author_sort | Ingrid Jenny Guldvik |
| collection | DOAJ |
| description | Background: After radical prostatectomy (RP), depending on stage, up to 40% of patients with prostate cancer (PCa) will experience biochemical failure (BF). Despite salvage therapy, approximately one-third of these patients will need permanent hormone therapy (pHT) and are at risk of progression to castration-resistant PCa (CRPC). Prognostic markers herald the need for neoadjuvant, adjuvant, or multimodal treatment. Objective: To evaluate the added value of blood LRG1 in predicting treatment failure in patients who have undergone radical prostatectomy (RP). Design, setting, and participants: We quantified LRG1 in serum or plasma sampled before radical prostatectomy from patients from the Martini-Klinik (Martini; n = 423), the Danish CuPCa cohort (CuPCa; n = 182), and Oslo University Hospital (OUH; n = 145). Outcome measurements and statistical analysis: The endpoints were BF, pHT, and CRPC. The association between LRG1 and survival outcomes was evaluated using Kaplan-Meier estimation and Cox proportional-hazards modeling. The added predictive value of LRG1 in nested models was estimated using the concordance index, time-dependent area under the receiver operating characteristic curve, and decision curve analysis. Results and limitations: In multivariable Cox models using preoperative characteristics, LRG1 was associated with an estimated lower risk of BF in the Martini cohort (adjusted hazard ratio [aHR] 0.68, 95% confidence interval [CI] 0.52–0.90) and in the CuPCa cohort (aHR 0.47, 95% CI 0.30–0.73). Using preoperative prognostic variables, our data showed that doubling of LRG1 was also associated with a lower risk of pHT receipt in the CuPCa cohort (aHR 0.43, 95% CI 0.20–0.93) and of CRPC development in the OUH cohort (aHR 0.32, 95% CI 0.15–0.69). Similar aHR values were observed using either preoperative or postoperative variables for all endpoints. Conclusions: PCa patients with high blood LRG1 are at lower risk of BF, pHT receipt, and progression to CRPC. Since LRG1 adds value to established prognostic models, new prognostic factor combinations including LRG1 should be considered in future studies. Patient summary: We measured concentrations of the blood-based protein LRG1 before surgery for prostate cancer. Patients with high LRG1 levels had better disease-free survival, suggesting that LRG1 can help in predicting prognosis. |
| first_indexed | 2024-04-11T23:35:36Z |
| format | Article |
| id | doaj.art-4bb9e8665eca453fb6a2b5e1d3055677 |
| institution | Directory Open Access Journal |
| issn | 2666-1683 |
| language | English |
| last_indexed | 2024-04-11T23:35:36Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Urology Open Science |
| spelling | doaj.art-4bb9e8665eca453fb6a2b5e1d30556772022-12-22T03:56:57ZengElsevierEuropean Urology Open Science2666-16832022-11-01456875Low Blood Levels of LRG1 Before Radical Prostatectomy Identify Patients with High Risk of Progression to Castration-resistant Prostate CancerIngrid Jenny Guldvik0Peder Rustøen Braadland1Shivanthe Sivanesan2Håkon Ramberg3Gitte Kristensen4Pierre Tennstedt5Andreas Røder6Thorsten Schlomm7Viktor Berge8Lars Magne Eri9Wolfgang Lilleby10Ian G. Mills11Kristin Austlid Taskén12Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Corresponding authors. Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway (I.J. Guldvik); Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headley Way, Headington, Oxford, UK (I.G. Mills).Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Norwegian PSC Research Center, Department of Transplantation Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, NorwayDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Urology, Oslo University Hospital, Oslo, NorwayDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, NorwayCopenhagen Prostate Cancer Center, Department of Urology, Center for Cancer and Organ diseases, Copenhagen University Hospital-Rigshospitalet, Copenhagen, DenmarkMartini-Klinik Prostate Cancer Centre, University Hospital Hamburg-Eppendorf, Hamburg, GermanyCopenhagen Prostate Cancer Center, Department of Urology, Center for Cancer and Organ diseases, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkMartini-Klinik Prostate Cancer Centre, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, Charité Universitätsmedizin Berlin, Berlin, GermanyInstitute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Urology, Oslo University Hospital, Oslo, NorwayInstitute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Urology, Oslo University Hospital, Oslo, NorwayDepartment of Oncology, Oslo University Hospital, Oslo, NorwayNuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, UK; Department of Oncology, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK; Patrick G. Johnston Centre for Cancer Research, Queen’s University of Belfast, Belfast, UK; Corresponding authors. Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway (I.J. Guldvik); Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headley Way, Headington, Oxford, UK (I.G. Mills).Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, NorwayBackground: After radical prostatectomy (RP), depending on stage, up to 40% of patients with prostate cancer (PCa) will experience biochemical failure (BF). Despite salvage therapy, approximately one-third of these patients will need permanent hormone therapy (pHT) and are at risk of progression to castration-resistant PCa (CRPC). Prognostic markers herald the need for neoadjuvant, adjuvant, or multimodal treatment. Objective: To evaluate the added value of blood LRG1 in predicting treatment failure in patients who have undergone radical prostatectomy (RP). Design, setting, and participants: We quantified LRG1 in serum or plasma sampled before radical prostatectomy from patients from the Martini-Klinik (Martini; n = 423), the Danish CuPCa cohort (CuPCa; n = 182), and Oslo University Hospital (OUH; n = 145). Outcome measurements and statistical analysis: The endpoints were BF, pHT, and CRPC. The association between LRG1 and survival outcomes was evaluated using Kaplan-Meier estimation and Cox proportional-hazards modeling. The added predictive value of LRG1 in nested models was estimated using the concordance index, time-dependent area under the receiver operating characteristic curve, and decision curve analysis. Results and limitations: In multivariable Cox models using preoperative characteristics, LRG1 was associated with an estimated lower risk of BF in the Martini cohort (adjusted hazard ratio [aHR] 0.68, 95% confidence interval [CI] 0.52–0.90) and in the CuPCa cohort (aHR 0.47, 95% CI 0.30–0.73). Using preoperative prognostic variables, our data showed that doubling of LRG1 was also associated with a lower risk of pHT receipt in the CuPCa cohort (aHR 0.43, 95% CI 0.20–0.93) and of CRPC development in the OUH cohort (aHR 0.32, 95% CI 0.15–0.69). Similar aHR values were observed using either preoperative or postoperative variables for all endpoints. Conclusions: PCa patients with high blood LRG1 are at lower risk of BF, pHT receipt, and progression to CRPC. Since LRG1 adds value to established prognostic models, new prognostic factor combinations including LRG1 should be considered in future studies. Patient summary: We measured concentrations of the blood-based protein LRG1 before surgery for prostate cancer. Patients with high LRG1 levels had better disease-free survival, suggesting that LRG1 can help in predicting prognosis.http://www.sciencedirect.com/science/article/pii/S2666168322019000BiomarkersCastration resistanceHormone treatmentNoninvasiveLRG1Prostate cancer |
| spellingShingle | Ingrid Jenny Guldvik Peder Rustøen Braadland Shivanthe Sivanesan Håkon Ramberg Gitte Kristensen Pierre Tennstedt Andreas Røder Thorsten Schlomm Viktor Berge Lars Magne Eri Wolfgang Lilleby Ian G. Mills Kristin Austlid Taskén Low Blood Levels of LRG1 Before Radical Prostatectomy Identify Patients with High Risk of Progression to Castration-resistant Prostate Cancer European Urology Open Science Biomarkers Castration resistance Hormone treatment Noninvasive LRG1 Prostate cancer |
| title | Low Blood Levels of LRG1 Before Radical Prostatectomy Identify Patients with High Risk of Progression to Castration-resistant Prostate Cancer |
| title_full | Low Blood Levels of LRG1 Before Radical Prostatectomy Identify Patients with High Risk of Progression to Castration-resistant Prostate Cancer |
| title_fullStr | Low Blood Levels of LRG1 Before Radical Prostatectomy Identify Patients with High Risk of Progression to Castration-resistant Prostate Cancer |
| title_full_unstemmed | Low Blood Levels of LRG1 Before Radical Prostatectomy Identify Patients with High Risk of Progression to Castration-resistant Prostate Cancer |
| title_short | Low Blood Levels of LRG1 Before Radical Prostatectomy Identify Patients with High Risk of Progression to Castration-resistant Prostate Cancer |
| title_sort | low blood levels of lrg1 before radical prostatectomy identify patients with high risk of progression to castration resistant prostate cancer |
| topic | Biomarkers Castration resistance Hormone treatment Noninvasive LRG1 Prostate cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2666168322019000 |
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