Parametric Cure Model versus Proportional Hazards Model in Survival Analysis of Breast Cancer and Other Malignancies

摘要

As cancer therapy has progressed dramatically, its goal has shifted toward cure of the disease (curative therapy) rather than prolongation of time to death (life-prolonging therapy). Consequently, the proportion of cured patients (c) has become an important measure of the long-term survival benefit derived from therapy. In 1949, Boag addressed this issue by developing the parametric log-normal cure model, which provides estimates of c and m where m is the mean of log times to death from cancer among uncured patients. Unfortunately, traditional methods based on the proportional hazards model like the Cox regression and log-rank tests cannot provide an estimate of either c or m. Rather, these methods estimate only the differences in hazard between two or more groups. In order to evaluate the long-term validity and usefulness of the parametric cure model compared with the proportional hazards model, we reappraised randomized controlled trials and simulation studies of breast cancer and other malignancies. The results reveal that: 1) the traditional methods fail to distinguish between curative and life-prolonging therapies; 2) in certain clinical settings, these methods may favor life-prolonging treatment over curative treatment, giving clinicians a false estimate of the best regimen; 3) although the Boag model is less sensitive to differences in failure time when follow-up is limited, it gains power as more failures occur. In conclusion, unless the disease is always fatal, the primary measure of survival benefit should be c rather than m or hazard ratio. Thus, the Boag lognormal cure model provides more accurate and more useful insight into the long-term benefit of cancer treatment than the traditional alternatives.