Potential benefits and harms of screening strategies for monoclonal gammopathy of undetermined significance in the US: A simulation study

Multiple myeloma (MM) is preceded by monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic premalignant condition. There are no recommendations for MGUS screening due to a lack of evidence regarding screening benefits. MGUS screening, however, could lead to early detection and timely treatment for MM. The decision to screen should balance potential benefits against harms, including overdiagnosis, which we defined as screening-detected MGUS that would not progress to MM during an individual's lifetime. We constructed MM natural history micro-simulation modeling, accounting for risk factors of MGUS/MM, including age, gender, race, and body mass index, to project the benefits and harms (overdiagnosis) of various MGUS screening strategies in the USA. We validated our model by comparing the simulated MM incidence with observed incidence from the Surveillance, Epidemiology, and End Results database for the years 2013 to 2017 across different ages groups. We simulated 80 screening strategies from 2003 to 2052, varying start and end ages and screening frequency, and generated an effectiveness frontier. We found that to early detect one MM patient across the strategies on the effectiveness frontier, there would be 3.6 to 5.9 individuals with screening-detected MGUS who would not progress to MM during their lifetime. Correspondingly, 78% to 86% of screening-detected MGUS cases did not progress to MM. Given the potential harms of overdiagnosis when screening general population, identifying and screening high-risk individuals is critical to maximize benefits and minimize harms. Micro-Abstract Monoclonal gammopathy of undetermined significance (MGUS) screening, could lead to early detection and timely treatment for multiple myeloma (MM), yet might increase the risk of overdiagnosis, where MGUS is detected but does not progress to MM. We constructed MM natural history micro-simulation modeling to project the benefits and harms (overdiagnosis) of various MGUS screening strategies in the USA. We found that to early detect one MM patient across the strategies on the effectiveness frontier, there would be 3.6 to 5.9 patients who were overdiagnosed. Correspondingly, 78% to 86% of screening-detected MGUS cases did not progress to MM.