What is disease-free survival?

Question

I am trying to make sense of what disease-free survival is (still new to medical research).

I was reading this article on the survival of patients after liver transplantation. In it, the author includes KM curves where one is overall survival (OS) and the other, disease-free survival (DFS). My initial understanding of DFS is survival time of patient for non-recurrence cohort. However, if that's the case then, the survival curve should be higher in DFS as compared to OS. The plots show OS being having better survival probability than DFS.

Does DFS mean:

• Still looking at death as event of interest, in addition patients that had recurred would have time-to-event as time to recurrence instead of time to death? or..
• Still looking at death as event of interest, in addition patients that had recurred would be censored?

Answer 1

Disease-free survival (DFS) does not use death as the event of interest. The event for DFS is the first clinical evidence of the return of disease. That means that the individual has lived at least that long, so overall survival (OS) for such patients will be no shorter than DFS. Thus the DFS curve tends to show "worse" survival than OS, but that's because they are measuring different things.

There are a couple of potential "gotchas" with DFS. One is the specific timing, as the return of disease is often detected at a scheduled clinical follow-up but the actual return of disease could have been at any time since the previous clinical visit. So DFS values aren't always very precise, and might better be handled as interval-censored data.

The second is how any particular study handles a death that happens before clinically detected return of disease. If death is found at autopsy to have been from that disease then the time of death could be treated as the time of disease return. If death is from another cause the time of death is an event for overall-survival analysis but is usually a censoring time for DFS analysis: the time to return of disease would have been longer than than the time to death.