Refined measurement of outcome for adjuvant breast carcinoma therapy.

Background: Traditional nonparametric statistical methods do not provide a quantitative measure of the lifetime benefit from adjuvant therapy. This deficiency makes it difficult to determine the long-term difference in impact between the two treatment arms of a clinical trial.

Methods: To assess the impact of breast carcinoma recurrence, parametric survival models were derived from two randomized, controlled clinical trials of adjuvant therapy for Stage II breast carcinoma. To assess time to death from causes other than breast carcinoma, actuarial models derived from 1980 Census data were used. These two models were then combined to estimate the mean time to event (MTE) as a function of patient age, with the event being either recurrence or death from other causes. The MTE was then used to measure the differential benefit between two arms of a clinical trial.

Results: In the first trial, differences in MTE between treatment groups varied from 2.7 years for 35-year-old patients to 1.4 years for 75-year-old patients. For this trial, the mechanism of survival benefit was an increase in time to recurrence. In the second trial, differences in MTE varied from 7.6 to 1.6 years over the same age ranges. For this trial, the mechanism of survival benefit was an increase in the likelihood of cure, i.e., an increase in the asymptote of the curve that represents proportion of patients without relapse.

Conclusions: When applied to data from controlled clinical trials, MTE offers a quantitative measure of long-term outcome from adjuvant therapy. The greatest benefit is achieved when therapy that increases the likelihood of cure is provided to young patients.