Reconsidering PFS (Progression Free Survival)

This month, the medical journal called The Lancet (a very influential journal) published an article called "Progression-Free Survival: It Is Time for a New Name." The authors of the article think we need to reconsider what we use Progression-Free Survival for, and even what we call it.

In some ways, the article is about something that really should only matter to oncologists, but I would argue that there is little about cancer and cancer research that doesn't matter to us as patients. Read on and I'll tell you why.

I write about Progression-Free Survival (or PFS) a lot. It comes up pretty much every time I describe a clinical trial, because it's one of the main "end-points" of most trials -- the ways they measure if a trial is successful. 

PFS is, simply, a measure of how long a patient has gone between starting treatment (or starting a trial) and having their disease progress (get worse), or die (of any cause). By using PFS as an end-point for a trial, researchers can compare different treatments to see which is most effective. Suppose a current treatment for patients had a median PFS of 36 months in a clinical trial (that is, if half of the patients had disease that came back before 36 months, and half had it come back later than 36 months, or not at all). A new treatment has a clinical trial where the PFS is 39 months. We can say that the new treatment is more effective than the old one, and make an argument that it should be approved for use.

The authors of the article make an interesting case as to why we shouldn't rely on PFS so much, and why we should change the name. The big reason behind their suggestion is that PFS doesn't really help patients as much as it seems to. 

According to the authors, "Disease progression is defined by the Response Evaluation Criteria in Solid Tumors as an increase in the sum of maximum tumor diameters of at least 20%, the development of any new lesions, or an unequivocal increase in non-measurable malignant disease." So in order to say that a patient's cancer has progressed after treatment, there has to be some way of measuring whether or not the cancer is worse than before the treatment. One way, for example, is to say that a solid tumor (that is, a non-blood cancer) has gotten 20% bigger. A 3 cm tumor is now 3.6 cm. 

But as they point out, in terms of the actual impact on a patient's life, a tumor that has grown from 3 cm to 3.5 cm is not considered to have "progressed" -- it has grown just under 20%. The patient is still considered "progression-free," and the treatment is considered successful. But is that really a "success" for the patient, who now knows that their tumor has gotten bigger, and not smaller?

To be clear -- that example is for a solid tumor, like for breast cancer or colon cancer, rather than a "liquid tumor" like lymphoma. The same 20% growth would hold for lymph nodes. But the other measures in that definition above still matter for blood cancers -- "new lesions" (the cancer showing up in a different place on a scan) or "unequivocal increase in non-measurable malignant disease" (the cancer is clearly gotten worse, and there's not argument about it).

There are other issues with PFS as well, including how the progression is measured, and who is measuring it. (A researcher who really wants the new treatment to work might measure a tumor as being a little bit smaller than it really is, even if they aren't aware that they are doing it. Here's an interesting look at the different ways that PFS measurement can be biased, if you're interested.)

The last issue with PFS has to do with the name itself. Calling it a measure of "survival" might be confusing to some people (it was for me, to be honest, when I first started reading about trials). "Survival" isn't really the thing being measured by PFS (though it does include death as counting against the PFS measurement). The authors suggest changing the name to "Progression-Free Interval," which puts the emphasis on progression, rather than survival.

I can see both sides of that, looking at it as a patient. I like the idea of "survival" as being part of the name -- it's a reminder that I'm still alive, even if the treatment has stopped working.

On the other hand, "survival" also makes the measurement seem more positive than it really is. I'm still alive, but that's not really the point. My disease is getting worse, and it might not be worse enough to even be "officially" worse if it's under 20%. Focusing on "survival" seems like it's avoiding the bad news. That doesn't do anything for my mental health.

In the end, I'd probably rather have it be called "Interval." It just seems more accurate. I have "Overall Survival" as a common statistic if I need a reminder that I' still alive. "Interval" reminds me that this is just one segment of my life as a cancer patient, and if the disease is progressing, it's time to move on to the next segment. That seems especially important to me as a Follicular Lymphoma patient. I might have a bunch of those intervals over 20 or 30 years.

The reason I find the article so fascinating is that it reminds me of how important language is for us as cancer patients. The words we use matter. Some people really like to think of themselves as cancer "warriors," who are "battling" the disease. Others hate the idea that this is a "fight" that they have to "win." Those words can help or hurt. We all use words differently.

I'm working on a project now that looks at the language we use to talk about cancer. I'm excited about it, and I hope I'll be able to tell you more about it soon. In my non-cancer life, thinking about how we use language is a big part of what I do. It's kind of fun to be able to combine those lives -- the cancer patient one and the non-cancer patient one. More on that soon.

In the meantime, I'm going to keep an eye out for reactions from the cancer community to this proposal to rethink how we use PFS and what we call it. And I'll pay more attention to how I describe PFS when I share information about trials.