In Reply Dr Burke asks why we focused on overall survival and not disease-specific survival in our Viewpoint,1 particularly among the elderly who face competing risks. We made the case that a marginal improvement in overall survival in an ideal population may be lost when that therapy is extrapolated to a real-world population. It is likely the case that a marginal benefit to disease-specific survival is also diluted or lost in the world because the mechanism of the loss is due to an increase in toxicity, frequent dose reductions, and discontinuations,2 leading to a tipping of the benefit/harm balance.