Importance: Cancer screening is often promoted as a means to save lives. The question of whether cancer screening truly saves lives is becoming increasingly relevant given the growing enthusiasm for multicancer detection blood tests (ie, liquid biopsies). It is possible in randomized clinical trials for screening to reduce deaths due to the targeted cancer without reducing deaths due to all causes. To explore the feasibility of powering studies for cancer-specific vs all-cause mortality, a series of sample size calculations was performed for selected cancers (breast, colorectal, liver, pancreas, and prostate) and for all cancers combined.
Observations: Randomized clinical trials of screening for an individual cancer typically require 100 000 or more participants to test its effect on cancer-specific mortality. Testing all-cause mortality requires trials of more than a million participants. However, the sample size requirements change markedly when considering a randomized clinical trial of screening for all cancers, as is envisioned when using multicancer detection blood tests. In this setting, the question of whether cancer screening reduces all-cause mortality can be reasonably addressed in a trial of fewer than 100 000 participants.
Conclusions and relevance: It is not feasible to test all-cause mortality when screening for an individual cancer. However, it is feasible to test all-cause mortality for multicancer screening because cancer deaths are such a large component of deaths in general. Observational data on the effects of cancer screening are misleading. Multicancer screening would entail tremendous costs and potentially substantial harms. For these reasons, a randomized clinical trial is mandatory not only to learn if multicancer screening saves lives, but also to learn how frequently it causes harm.