Interpreting Net Survival: What We Estimate Versus What We Think We Estimate

Net survival is conventionally defined as ``survival if cancer were the only possible cause of death'', an estimand corresponding to cancer-specific mortality alone. The Pohar Perme estimator targets this by removing general population other-cause mortality from observed total mortality, but achieves it only when cancer patients experience the same other-cause mortality as the general population. However, cancer patients often experience elevated other-cause mortality due to baseline health differences and treatment-induced effects. Using recent theoretical work decomposing total mortality into four components (cancer deaths, baseline health differences, treatment-induced other-cause deaths, and general population other-cause mortality), we show that the Pohar Perme estimator delivers the sum of cancer deaths, baseline differences, and treatment-induced deaths, falling short of its intended estimand whenever either source of excess is present. From Botta \textit{et al}, we present empirical evidence showing relative risk of other-cause deaths ranging from 1.0 (colorectal cancer) to 4.0+ (head and neck cancers), and calculations demonstrating that net survival can substantially underestimate cancer-specific survival probability when relative risk exceeds 1.0. Critically, treatment-induced other-cause deaths represent irreducible causal pathways from cancer to death that cannot be eliminated through better stratification. We recommend interpreting net survival as ``survival where general population other-cause mortality is removed'' rather than as a causal counterfactual, and call for more precise language in cancer epidemiology.