Low Blood Levels of LRG1 Before Radical Prostatectomy Identify Patients with High Risk of Progression to Castration-resistant Prostate Cancer.

Autor:	Guldvik IJ; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Braadland PR; 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, Norway., Sivanesan S; Department 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, Norway., Ramberg H; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway., Kristensen G; Copenhagen Prostate Cancer Center, Department of Urology, Center for Cancer and Organ diseases, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark., Tennstedt P; Martini-Klinik Prostate Cancer Centre, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Røder A; Copenhagen 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, Denmark., Schlomm T; Martini-Klinik Prostate Cancer Centre, University Hospital Hamburg-Eppendorf, Hamburg, Germany.; Department of Urology, Charité Universitätsmedizin Berlin, Berlin, Germany., Berge V; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Urology, Oslo University Hospital, Oslo, Norway., Eri LM; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Urology, Oslo University Hospital, Oslo, Norway., Lilleby W; Department of Oncology, Oslo University Hospital, Oslo, Norway., Mills IG; Nuffield 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., Taskén KA; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	European urology open science [Eur Urol Open Sci] 2022 Oct 04; Vol. 45, pp. 68-75. Date of Electronic Publication: 2022 Oct 04 (Print Publication: 2022).
DOI:	10.1016/j.euros.2022.09.002
Abstrakt:	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. (© 2022 The Author(s).)
Databáze:	MEDLINE
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