Abstract Recent studies have reported increases in early-onset cancer cases (diagnosed under age 50) and raised questions about whether the increase is related to earlier diagnosis from non-specific medical tests as reflected by decreasing tumor-size-at-diagnosis (apparent effects) or actual increases in underlying cancer risk (true effects), or both. The classic Multi-Stage Clonal Expansion (MSCE) model assumes cancer detection at the first malignant cell's emergence, although later modifications have included lag-times or stochasticity in detection to represent the delay in tumor detection. Here, we introduced an approach to explicitly incorporate tumor-size-at-diagnosis in the MSCE framework accounting for improvements in cancer detection over time to distinguish between apparent and true increases in early-onset cancer incidence. The model was structurally identifiable and provided better parameter estimation than the classic model. The model was applied to colorectal, breast, and thyroid cancers to examine changes in cancer risk while accounting for detection improvements over time in three representative birth cohorts (1950-1954, 1965-1969, and 1980-1984). The analyses suggested accelerated carcinogenic events and shorter mean sojourn times (the average time from the first malignant cell emergence to cancer detection) in more recent cohorts. Further, using this model to examine the screening impact on the incidence of breast and colorectal cancers, which both have established screening protocols, provided results that align with well-documented differences in screening effects between these cancers. These findings underscore the importance of incorporating tumor-size-at-diagnosis in cancer modeling and support true increases in early-onset cancer risk in recent years for breast, colorectal, and thyroid cancer.
Mirzaei et al. (Fri,) studied this question.