Prognostic associations were robust for MPO/DNA, H3Cit, and NE, but not for cell free DNA.<h4>Conclusion</h4>Elevated NET levels predict poorer outcomes in patients with cancer independent of specimen source and most analytic modalities (except cell free DNA), supporting NETs as a promising biomarker for risk stratification and precision oncologic decision making.<h4>Systematic review registration</h4>https://www.crd.york.ac.uk/PROSPERO/view/CRD42025596821. The gene discussed is MPO; the disease is cancer.