Line J H Rasmussen1, Martin Schultz2, Kasper Iversen2, Jesper Eugen-Olsen3, Morten Helms4, Kim David4, Andreas Kjaer5, Anne-Mette Lebech6, Gitte Kronborg7. 1. Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark; Department of Psychology and Neuroscience, Duke University, 2020 W Main St, Suite 201, Durham, NC 27708, USA. Electronic address: line.jee.hartmann.rasmussen@regionh.dk. 2. Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Borgmester Ib Juuls Vej 1, DK-2700 Herlev, Denmark. 3. Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. 4. Department of Infectious Diseases, Copenhagen University Hospital Amager and Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. 5. Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Juliane Maries Vej 8, DK-2100 Copenhagen Ø, Denmark; Cluster for Molecular Imaging, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. 6. Department of Infectious Diseases, Rigshospitalet, Esther Møllers Vej 6, DK-2100 Copenhagen Ø, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark. 7. Department of Infectious Diseases, Copenhagen University Hospital Amager and Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark.
Abstract
BACKGROUND: Accurate first-line diagnostics are essential for early recognition of cancer but also to identify patients free of disease. The biomarker soluble urokinase plasminogen activator receptor (suPAR) is elevated in patients with cancer or non-malignant disease compared to disease-free patients. We tested if low suPAR could be used to identify disease-free patients in an accelerated cancer diagnostics program, including ruling out cancer. METHODS: Patients with serious nonspecific symptoms and signs of cancer (NSSC) were included at the Diagnostic Outpatient Clinic, Copenhagen University Hospital Hvidovre, Denmark. Data from a clinical examination, including blood tests and imaging, was combined with national registry data on diagnoses and mortality. The association between blood suPAR and the primary outcome of disease-free (i.e., absence of incident disease and mortality) within 1-year follow-up was analysed with logistic regression analysis. RESULTS: Of 1583 patients included, 349 (22.0%) were diagnosed with cancer, 837 (52.9%) with non-malignant disease, and 392 (25.8%) were disease-free within one year. Admission suPAR was significantly lower in disease-free patients compared to patients with cancer or non-malignant disease (P < 0.001), area under the curve 0.67 (95% confidence interval (CI): 0.64-0.70). The highest positive predictive value (PPV) for the outcome of disease-free was 0.55 (95% CI: 0.41-0.68) at a suPAR of 1.65 ng/mL. Patients who died had significantly higher suPAR compared to patients who survived in all disease subgroups. The AUC of suPAR for 1-year mortality was 0.80 (95% CI: 0.77-0.83). CONCLUSIONS: suPAR was significantly lower in disease-free individuals compared to patients with cancer or other conditions, but the PPV was not sufficiently high to terminate further clinical investigation with appropriate safety. Elevated suPAR may be a useful prognostic marker for adverse outcomes.
BACKGROUND: Accurate first-line diagnostics are essential for early recognition of cancer but also to identify patients free of disease. The biomarker soluble urokinase plasminogen activator receptor (suPAR) is elevated in patients with cancer or non-malignant disease compared to disease-free patients. We tested if low suPAR could be used to identify disease-free patients in an accelerated cancer diagnostics program, including ruling out cancer. METHODS:Patients with serious nonspecific symptoms and signs of cancer (NSSC) were included at the Diagnostic Outpatient Clinic, Copenhagen University Hospital Hvidovre, Denmark. Data from a clinical examination, including blood tests and imaging, was combined with national registry data on diagnoses and mortality. The association between blood suPAR and the primary outcome of disease-free (i.e., absence of incident disease and mortality) within 1-year follow-up was analysed with logistic regression analysis. RESULTS: Of 1583 patients included, 349 (22.0%) were diagnosed with cancer, 837 (52.9%) with non-malignant disease, and 392 (25.8%) were disease-free within one year. Admission suPAR was significantly lower in disease-free patients compared to patients with cancer or non-malignant disease (P < 0.001), area under the curve 0.67 (95% confidence interval (CI): 0.64-0.70). The highest positive predictive value (PPV) for the outcome of disease-free was 0.55 (95% CI: 0.41-0.68) at a suPAR of 1.65 ng/mL. Patients who died had significantly higher suPAR compared to patients who survived in all disease subgroups. The AUC of suPAR for 1-year mortality was 0.80 (95% CI: 0.77-0.83). CONCLUSIONS:suPAR was significantly lower in disease-free individuals compared to patients with cancer or other conditions, but the PPV was not sufficiently high to terminate further clinical investigation with appropriate safety. Elevated suPAR may be a useful prognostic marker for adverse outcomes.