Design of randomized controlled trials to estimate cancer-mortality reductions from multicancer detection screening

Area of Science:

• Oncology
• Clinical Trials
• Biostatistics

Background:

• Determining the life-saving potential of multicancer detection (MCD) tests necessitates rigorous randomized controlled trials (RCTs).
• This study aimed to inform the design of future MCD RCTs by estimating potential cancer mortality outcomes.

Purpose of the Study:

• To estimate cancer mortality reductions, required sample sizes, and statistical power for hypothetical MCD RCTs.
• To evaluate the impact of various RCT and MCD test parameters on study outcomes.

Main Methods:

• Utilized the Hu-Zelen model, a validated tool previously employed for the National Lung Screening Trial (NLST).
• Simulated RCTs involving 100,000 participants per arm, undergoing 5 annual screens for 9 cancer types.
• Assessed outcomes across different screening frequencies, participant demographics, and MCD test performance characteristics.

Main Results:

• A base-case RCT design demonstrated 87%-89% power to detect a 9%-10% mortality reduction over 7-9 years.
• Lung cancer accounted for the majority of prevented deaths (64%-66%), followed by colorectal cancer (8%-10%).
• Limited power was observed for detecting mortality reductions at individual non-lung, non-colorectal cancer sites.

Conclusions:

• Large-scale MCD RCTs are projected to have 89% power to detect a ~10% cancer mortality reduction within 7-9 years.
• The estimated Number Needed to Screen (NNS) for MCD RCTs is comparable to mammographic screening.
• While lung cancer dominates prevented deaths, other cancers contribute meaningfully, though isolating their specific mortality reductions requires further study or higher risk populations.