What is the conventional definition of recurrence-free survival? Hello to all the biostatisticians and epidemiologists out there,
I have looked up and down for a standard definition of recurrence-free survival, and the issue I'm having is determining if the standard includes DEATH as an event or not.  I have seen some studies censor at death and others include death along with recurrences as events.  If death is traditionally included as an event, what is the rationale for that?  It certainly is not a recurrence.  Also, is there a difference between relapse-free survival and recurrence-free survival?
Thanks for your help!
 A: As you have seen, both definitions are acceptable, mostly because both options have problems. Even the FDA does not seem to express a preference. Quoting from Guidance for Industry Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics (DFS is Disease Free Survival):

The definition of DFS can be complicated, particularly when deaths are noted without prior tumor progression documentation.  These events can be scored either as disease recurrences or as censored events.  Although all methods for statistical analysis of deaths have some limitations, considering all deaths (deaths from all causes) as recurrences can minimize bias.  DFS can be overestimated using this definition, especially in patients who die after a long period without observation.  Bias can be introduced if the frequency of long-term follow-up visits is dissimilar between the study arms or if dropouts are not random because of toxicity.  Some analyses count cancer-related deaths as DFS events and censor noncancer deaths.  This method can introduce bias in the attribution of the cause of death.  Furthermore, any method that censors patients, whether at death or at the last visit, assumes that the censored patients have the same risk of recurrence as noncensored patients.   

A: The issue of death in any non-fatal disease is a problem in many survival analysis studies. I have generally seen this handled two ways, and have not seen anyone arguing that there is a particular dominant or unified standard.
The first way is to consider death to be one of your outcomes. So your event becomes "Event OR All-cause Mortality". This may be more intuitive and, conveniently, if you think your disease may be driving some of those deaths, may capture additional information. It's also the most amenable to a straightforward survival analysis.
The second method is to treat death as a competing risk. Then, the usual approach is to treat death-events as censored for the outcome of interest at time of death, and analyze from there. This essentially asks "What would your hazard of death have been, had you not died for some other reason?". Especially if you think death is something of an "uninteresting" outcome, this may be a workable approach.
As both are pretty approachable using standard software, I'd consider doing both, and seeing if your estimates end up being substantially different.
A: 
If death is traditionally included as an event, what is the rationale for that? It certainly is not a recurrence.

I faced the same issue as you. The interest that I can see is when the outcome is "Does the patient's state deteriorate due to the disease?" In that case, you can define an event as being:

*

*a death due to the disease

*a recurrence

And you can define a censored observation as being:

*

*a death whose cause is unknown or not due to the disease

*a loss to follow-up

But in my opinion, we should rather call this outcome progression-free survival (PFS). In all cases, we should always precise the definition we use in our communications/publications: what defines an event.
According to several cancer MD researchers whom I have been working with, if the cause of death is unknown, then we should never consider it as an event when studying RFS/PFS. Otherwise we would be confusing it with overall survival (OS, all-cause-mortality) while one objective of studying RFS/PFS is in fact to focus on the disease.
