Biased methods for estimating local and distant failure rates in breast carcinoma and a "commonsense" approach

Background. Several methods are used to estimate risks of local and distant . failure after treatment of breast carcinoma. The authors' Purpose was to present a physician-friendly description of the potential bias in these met hods, and to suggest an improvement. Methods. The cumulative incidence based on first event (cumulative incidenc e [CI]) and Kaplan-Meier method based on first (KM[1st]) or all (KM[any]) e vents, are applied to a database comprising 2521 women treated for breast c arcinoma at the same institution and observed for more than 20 years. The a uthors relate these estimates to the region containing all possible estimat es of failure rate. This region contains the "true" risk (net risk, or risk that would be observed in the absence of competing risks) of local or dist ant failure. Results. The CI estimate is the lowest possible estimate of the true failur e rate. Under certain "commonsense" assumptions, the CI estimate is below t he lowest possible estimate of risk of failure. The KM(1st) estimate is hig her than the CI estimate and lower than the KM(any) estimate. Under the sam e commonsense assumptions, the KM(1st) method also underestimates the true failure rate. Conclusions. Methods based on time to first event such as Cl and KM(1st) un derestimate the true risk. In the design of clinical trials, consideration should be given to longer follow-up and the KM(any) method of analyzing res ults because it provides a less biased estimate. Cancer 2001;92:2220-7. (C) 2001 American Cancer Society.