This PRISMA 2020-compliant systematic review synthesized evidence from 82 studies (2000–2025) on the epidemiology, clinical and radiological features, pathophysiology, biomarkers, and treatment strategies of ischemic stroke secondary to cancer-associated coagulopathy (CAC) in patients with solid tumors.
CAC-related stroke occurs most often within 6 months of cancer diagnosis, is predominantly cryptogenic (~40–51%), and is strongly linked to adenocarcinoma (especially lung and pancreatic). The hallmark MRI pattern is multi-territory infarcts in >2 vascular territories ('three territories sign'). D-dimer is the most consistent biomarker for recurrence and mortality. Thirty-day mortality ranges from 25–50%, cumulative stroke recurrence reaches 16% at 6 months, and 75%+ of survivors at 3 months have mRS ≥3.
- Evidence base is predominantly retrospective and observational (57 retrospective, 21 prospective cohorts; only 2 RCTs), limiting causal inference and treatment conclusions. - No quantitative meta-analysis was possible due to marked heterogeneity in study design, CAC definitions, D-dimer assay platforms/units, and outcome measures. - Review protocol was not prospectively registered (PROSPERO), and only English- and Spanish-language studies were included, introducing possible reporting and language bias.
In any patient with cryptogenic stroke and multi-territory DWI infarcts, especially with adenocarcinoma (lung or pancreatic), check D-dimer early—levels ≥5.5 µg/mL carry >99% specificity for cancer-associated stroke and should prompt urgent malignancy workup. For secondary prevention, LMWH or a DOAC is preferred over warfarin; use LMWH first-line in GI malignancies given higher DOAC bleeding risk.
