Background: Lead-time bias occurs when cancer is detected earlier in time, but with no change in lifespan. Cause of death is not susceptible to lead-time bias; therefore, stratifying cause of death by cancer stage informs the potential for lead-time bias in early detection across cancer types. Methods: Using recent data from 17 US Surveillance, Epidemiology, and End Results (SEER) cancer registries for 1 152 610 first incident primary cancers among patients aged 50–84 years at diagnosis in 2006–2010, we evaluated proportional causes of death by cancer type and uniformly classified stage at diagnosis (American Joint Committee on Cancer, 6th edition), following or extrapolating all patients until death. Results: A minority of cancer patients diagnosed at stages I–II (27%) went on to die from their index cancer, whereas most stage IV cancer patients (85%) did. For patients diagnosed with stage I cancer at all sites combined, an estimated 26% of deaths were due to the index cancer, 61% due to non-cancer causes, and 12% due to a subsequent primary (non-index) cancer. At stage II, 27% of deaths were due to the index cancer, 60% due to non-cancer causes, and 13% due to a non-index cancer. In contrast, at stage IV, 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. Leading causes of non-index cancer death (lung, pancreas, and colorectal) and non-cancer death (heart disease and COPD) at each stage were similar to those in the general US population. Non-White racial/ethnic groups, including Hispanics and non-Hispanic Blacks, Asian Americans/Pacific Islanders, and American Indians/Alaska Natives, experienced a higher percentage of deaths from stages I–II cancer than non-Hispanic Whites. Conclusions: Across all cancer types, the percentage of patients who went on to die from their cancer was three times greater at stage IV than at stages I–II. As mortality patterns are not influenced by lead-time bias, these data suggest that earlier stage at diagnosis is broadly, if not uniformly, associated with substantially reduced risk of cause-specific death from cancer; therefore, early detection is likely to improve outcomes across cancer types, including those currently unscreened.

*Percentages may not sum to 100% due to rounding.