Avoiding lead-time bias by estimating stage-specific proportions of cancer and non-cancer deaths

Purpose: Understanding how stage at cancer diagnosis influences cause of death, an endpoint that is not susceptible to lead-time bias, can inform population-level outcomes of cancer screening. Methods: Using data from 17 US Surveillance, Epidemiology, and End Results registries for 1,154,515 persons aged 50–84 years at cancer diagnosis in 2006–2010, we evaluated proportional causes of death by cancer type and uniformly classified stage, following or extrapolating all patients until death through 2020. Results: Most cancer patients diagnosed at stages I–II did not go on to die from their index cancer, whereas most patients diagnosed at stage IV did. For patients diagnosed with any cancer at stages I–II, an estimated 26% of deaths were due to the index cancer, 63% due to non-cancer causes, and 12% due to a subsequent primary (non-index) cancer. In contrast, for patients diagnosed with any stage IV cancer, 85% of deaths were attributed to the index cancer, with 13% non-cancer and 2% non-index-cancer deaths. Index cancer mortality from stages I–II cancer was proportionally lowest for thyroid, melanoma, uterus, prostate, and breast, and highest for pancreas, liver, esophagus, lung, and stomach. Conclusion: Across all cancer types, the percentage of patients who went on to die from their cancer was over three times greater when the cancer was diagnosed at stage IV than stages I–II. As mortality patterns are not influenced by lead-time bias, these data suggest that earlier detection is likely to improve outcomes across cancer types, including those currently unscreened.