Cancer Prevention Clinical Trials: Advances and Challenges

Prevention of cancer is an appealing strategy to reduce the burden of illness associated with cancer, but despite the rapidly advancing understanding of the early phases of carcinogenesis, translation of biologic insights into actionable public health strategies has been challenging. Phase III clinical trials have historically required large numbers of participants and lengthy durations to show effects in the minority of participants who develop cancer during the finite span of each trial. Early-phase trials help to refine intervention strategies and provide preliminary human safety and efficacy data to justify phase III trials. Recent advances in trial methodology and developments in immunopreventive strategies have energized the field of cancer prevention and provide potential paths for prevention of multiple cancer types. In this review we discuss the history and current state of cancer prevention trials, with a focus on overcoming inherent biologic and methodologic barriers to preventive agent development.