Endpoint-specific mortality associated with malignancy among adults with sepsis or septic shock: a systematic review and meta-analysis

Sepsis is a major global health challenge and increasingly affects patients with complex conditions such as malignancy. Prior studies suggest higher mortality in this population, but interpretation is limited by aggregation of heterogeneous endpoints. We conducted a systematic review and meta-analysis to clarify endpoint-specific prognostic associations between malignancy and mortality in adults with sepsis or septic shock.

This study was registered in PROSPERO (CRD420251141216). PubMed, Embase, Web of Science, Cochrane Library and Epistemonikos were searched through 16 September 2025, for studies comparing all-cause mortality between sepsis patients with and without malignancy. Mortality endpoints were grouped as ICU, in-hospital, early, intermediate and extended follow-up mortality. Crude odds ratios (ORs) were estimated using random-effects meta-analysis. Subgroup, meta-regression and sensitivity analyses were performed to explore heterogeneity and assess consistency.

Among 105 eligible studies comprising 20,089,138 participants, 85 studies contributing 101 endpoint estimates were included in the primary synthesis. Pooled estimates were elevated across endpoints: ICU (OR 1.21, 95% CI 0.94-1.56), in-hospital (OR 1.90, 95% CI 1.69-2.13), early (OR 1.81, 95% CI 1.59-2.06), intermediate (OR 2.28, 95% CI 1.72-3.03) and extended follow-up mortality (OR 2.41, 95% CI 1.70-3.42). Associations were sustained for haematologic malignancy, concentrated in in-hospital and early mortality for metastatic disease and more modest for solid tumours. Sensitivity analyses were directionally consistent, although risk ratio estimates were generally smaller than ORs. Exploratory meta-regression suggested that severity-related covariates may contribute to heterogeneity.

Malignancy was associated with higher mortality among adults with sepsis or septic shock, with variation across mortality endpoints and clinical contexts. These findings support endpoint-specific prognostic assessment and highlight the need for future studies to incorporate more granular cancer characteristics. Because the primary estimates were unadjusted, results represent overall prognostic associations rather than independent causal effects.