ASCO 2012, Chicago, USA

Effects of age on treatment and outcomes in women with stage IB-IIB cervical cancer

Dr Don Dizon – Brown University, Providence, USA

ecancer.tv now turns to the very important topic of age and whether it should be a determinant in therapy. Now, in a number of malignancies it is being discussed widely and Dr Don Dizon, you’ve been looking at cervical cancer. Can you tell me first of all what’s your first shot, is age important for determining treatment?

I believe that age is important, no matter what the malignancy is. What’s interesting about cervical cancer is that disease can be approached in different ways and it’s fine. So a woman with early stage cervical cancer could undergo treatment surgically with removal of the uterus and cervix or she can undergo non-surgical therapy with chemotherapy and radiation. What we were interested in looking at was whether age was associated with one versus the other.

And you’ve been studying this and you had patients above and below 65 years of age. What did you do?

What we did was look at our experience at Women and Infants Hospital of how we approached cervical cancer. We were primarily interested in women presenting with what would be considered curative intent therapy, so women with early stage cervical cancer; generally speaking, it’s disease confined to the cervix with some involvement of the supportive tissue around it, or the parametria, up to maybe one-third involvement distally to the vagina.

And how much were clinicians being influenced by chronological age?

It looked like age was being considered but the other thing we were able to do was construct a score of comorbidity alongside age as well. So that’s not done clinically and usually we use age as a surrogate for comorbidity scores as well. But it did appear in the work we’re presenting here at ASCO that age was being used as a determinant of how surgeons, gynaecologic oncologists, were approaching the disease.

So in the results to this, what kinds of things came out of this?

It looked like as a woman got older, the likelihood of a surgical approach was not as prominent. So there was a clear delineation of primary chemotherapy with radiation in women over 65 versus a surgical approach.

How much difference did that make to outcomes?

It appeared to be very striking and this was actually a surprise to me. The women who underwent surgery specifically appeared to have worse outcomes in terms of both all-cause mortality as well as disease-specific mortality. Specifically, women over 65 treated with surgery had almost a sevenfold higher risk of dying which was statistically significant. Their cancer-specific mortality was threefold higher but the range on that was high so it was not statistically significant. But I think a threefold higher risk of death is clinically significant.

So what can you say, coming out of this, in terms of clinical implications then?

I believe if you’re presenting or treating a woman over 65 that it’s going to be very important you consider both the age as well as the physical status when you’re approaching treatments but our data lends support to a non-surgical yet curative approach to the older woman with cervical cancer.

You say it’s an uncomfortable mix between comorbidities and chronological age, so you’ve not gone completely down the path of replacing chronological age with some other form of age?

Right. I think this whole idea of using the comorbidity index, the issue is it’s a research tool but it’s very difficult to use it on a point of care process. So it’s not information that we have ready access to and it’s not well-established of what cut-offs to use with the comorbidity score. What we use now is performance status, alongside age that also can possibly help us choose the right therapy for older women.

And, of course, with earlier stages of cervix cancer you definitely can cure therefore even if the woman is quite old you’ve got to consider what is the optimum treatment. Have you clarified this?

I believe that is true that is it a cancer that can be cured but I believe our data also suggests that with our curative approaches we need to consider what else is going on in that woman’s life. The fact that surgery was associated with such a high risk of all-cause mortality is telling because that means these women were dying of causes other than their cervical cancer.

So you’d put some type of restraint on the enthusiasm for going for surgery?

And perhaps what we’ve done with this project is beg the question of whether or not a curative treatment for early stage cervical cancer needs to be done.

Because you can do really well without it.

Yes, and because the likelihood is you’re going to die of something else.

Don, it’s great to hear what you’ve got to say about that very important and quite common situation that clinicians are faced with. Another situation now for clinicians, well it used to be whether or not to use erythropoietin stimulating agents. Of course, things have changed, but because there was a change you’ve got some data on this, haven’t you? A very big study, tell me about the study you’ve been doing.

This data is being presented by my colleague, Kim Dickinson at ASCO this year. Just to put this in context for your viewing audience, in June 2008 data was coming out that the use of erythropoietin stimulating agents may actually be associated with an increased risk of mortality so here in the United States the Food and Drug Administration sent out what’s called a clinical alert. They essentially wanted us not to use ESAs for chemotherapy induced anaemia, particularly if the treatment intent was curative. This caused a bit of a controversy within our field because we use ESAs to reduce the amount of transfusions we give to people unnecessarily. Without ESAs the concern was we were going to see an increase in the use of transfusions.

And this was in patients with breast and gynaecologic malignancies?

It is actually across all malignancies with this sort of reassessment of whether or not you should use ESAs.

And in your context?

But in our context it was in the context of gynaecologic and breast cancers, yes.

So what came out of this study?

We decided to look at this question of whether or not ESA use and discontinuation was affecting transfusion rates. In our experience, we were able to track our patients prior to what’s called the FDA clinical alert and then for the year following the FDA clinical alert. We had a large sample of over 700 patients that we looked at and it appeared that, as you would expect, following the clinical alert there was a two-thirds reduction in the amount of ESA use we were seeing at our centre, but surprisingly there was no change at all in the rates of transfusion. So it stayed at 44% despite the discontinuation of ESAs.

There are some lessons coming out of this, aren’t there? Because clinicians always want to do the best for their patient and they have a desire to do more if possible. What’s the lesson coming out of it?

I think there are a couple of lessons and also a very intriguing question. One of the lessons is because we didn’t see this transfusion rate increase with the reduction in ESA use, we are probably at a point where we’re not treating numbers anymore. So, instead of saying “Oh, your haemoglobin is now 9, it’s a prompt for me to use ESA so it doesn’t fall lower,” without ESAs now we’re saying, “Your haemoglobin is 9 but you’re not having any symptoms so let’s just watch.” I believe that’s actually what’s happening now versus, “Your haemoglobin is 9, I need to transfuse you.” We now have evidence that that is not what’s happened.

A bit of a vote for the watchful waiting and for good doctoring.

Correct. It’s good doctoring because you’re treating symptoms and you’re not treating numbers, yes.

Don Dizon, it’s great to have you doing some good doctoring with us here at the ASCO meeting, thank you very much.

Thank you very much.