Latent Class Survival Models Linked by Principal Stratification to Investigate Heterogenous Survival Subgroups Among Individuals With Early-Stage Kidney Cancer

Rates of kidney cancer have been increasing, with small incidental tumors experiencing the fastest growth rates. Much of the increase could be due to increased use of CT scans, MRIs, and ultrasounds for unrelated conditions. Many tumors might never have been detected or become symptomatic in the past. This suggests that many patients might benefit from less aggressive therapy, such as active surveillance by which tumors are surgically removed only if they become sufficiently large. However, it has been difficult for clinicians to identify subgroups of patients for whom treatment might be especially beneficial or harmful. In this work, we use a principal stratification framework to estimate the proportion and characteristics of individuals who have large or small hazard rates of death in two treatment arms. This allows us to assess who might be helped or harmed by aggressive treatment. We also use Weibull mixture models. This work differs from much previous work in that the survival, classes upon which principal stratification is based are latent variables. That is, survival class is not an observed variable. We apply this work using Surveillance Epidemiology and End Results-Medicare claims data. Clinicians can use our methods for investigating treatments with heterogenous effects.