TITLE:
Parametric Cure Model versus Proportional Hazards Model in Survival Analysis of Breast Cancer and Other Malignancies
AUTHORS:
Shunzo Maetani, John W. Gamel
KEYWORDS:
Cancer Survival Analysis; Boag Model; Cox Model; Cure
JOURNAL NAME:
Advances in Breast Cancer Research,
Vol.2 No.4,
September
9,
2013
ABSTRACT: 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.