Current estimates of the cure fraction: a feasibility study of statistical cure for breast and colorectal cancer.

BACKGROUND The probability of cure is a long-term prognostic measure of cancer survival. Estimates of the cure fraction, the proportion of patients "cured" of the disease, are based on extrapolating survival models beyond the range of data. The objective of this work is to evaluate the sensitivity of cure fraction estimates to model choice and study design. METHODS Data were obtained from the Surveillance, Epidemiology, and End Results (SEER)-9 registries to construct a cohort of breast and colorectal cancer patients diagnosed from 1975 to 1985. In a sensitivity analysis, cure fraction estimates are compared from different study designs with short- and long-term follow-up. Methods tested include: cause-specific and relative survival, parametric mixture, and flexible models. In a separate analysis, estimates are projected for 2008 diagnoses using study designs including the full cohort (1975-2008 diagnoses) and restricted to recent diagnoses (1998-2008) with follow-up to 2009. RESULTS We show that flexible models often provide higher estimates of the cure fraction compared to parametric mixture models. Log normal models generate lower estimates than Weibull parametric models. In general, 12 years is enough follow-up time to estimate the cure fraction for regional and distant stage colorectal cancer but not for breast cancer. 2008 colorectal cure projections show a 15% increase in the cure fraction since 1985. DISCUSSION Estimates of the cure fraction are model and study design dependent. It is best to compare results from multiple models and examine model fit to determine the reliability of the estimate. Early-stage cancers are sensitive to survival type and follow-up time because of their longer survival. More flexible models are susceptible to slight fluctuations in the shape of the survival curve which can influence the stability of the estimate; however, stability may be improved by lengthening follow-up and restricting the cohort to reduce heterogeneity in the data.