Cancer and survivorship have played an unusually high-profile role in the current campaign for the Presidency. Elizabeth Edwards and Rudy Giuliani come to mind.
Today, the Lancet—a well respected and authoritative British medical journal known among many for sometimes highlighting controversial topics to promote discussion—included a letter to the editor which concluded that Senator McCain had a 24% chance of surviving 10 years after his treatment for melanoma in 2000.
The author of the letter goes on to say that with regard to future risk, another data source suggested that the risk of dying from melanoma is constant over time, meaning that there is no expectation that the majority of deaths from melanoma occur shortly after the disease is diagnosed. The author calculated that risk of death at essentially 12% per year for the foreseeable future of a McCain presidency. He then cut that to 6% given the Senator's negative lymph node dissection.
The letter is short, the statistics complicated, and in my personal opinion, they lead the reader to an incorrect conclusion.
I have assiduously avoided getting involved in predicting the cancer outcome of the Presidential candidates, starting with some of the questions I began receiving a couple of years ago. But when the statistics may have an influence on a campaign and are presented in a manner that may not be consistent with the evidence, then I think it is appropriate to shine some light on the situation.
A recent article in the New York Times by Lawrence Altman, MD goes into great detail about McCain’s medical history with regard to his various melanomas which have been diagnosed since 1993.
The melanoma episode that has caused the greatest concern was in 2000, when one was diagnosed on his face. Following removal of that lesion, which was 2.2 mm thick (an important factor in determining outlook and treatment for particular patient’s melanoma), he had a radical dissection of the lymph nodes on the left side of his neck. That surgery showed no evidence that the cancer had spread to the lymph nodes.
Now, what do we know about Senator McCain and other patients with similar histories of melanoma and how does it compare to the information the letter writer cited in terms of anticipated survival?
The Lancet letter says, “McCain’s melanoma fell into the higher-risk categories identified in that study: the tumour was 2.2 mm thick, placing it into the second highest risk category (T3); McCain was older than 60 years at diagnosis; he is male; and his lesion was not on an extremity. As a result, using the prognostic model, his predicted 10-year survival at the time of diagnosis was only 24%.”
I went back and read the article the writer used as a reference. It was published in the Annals of Internal Medicine, a highly regarded medical journal, in 1996. It was written by very well-qualified experts in the field of melanoma.
The researchers examined the records of 488 patients who had no evidence of spread of their melanoma at the time of diagnosis. They followed the patients for 10 to 20.5 years after surgery. Then, they looked at various characteristics of the melanomas to link survival time with these characteristics.
From this research they found four factors were useful in creating a model to predict survival at 10 years: the thickness of the melanoma, the site of the primary cancer, the age of the patient and the patient’s sex.
In considering Senator McCain, who was over 60 at the time of his diagnosis in 2000, the 10 year predicted survival looking forward from the time he was diagnosed was indeed 24%.
However—and this is an important however—this is a “single point” type of observation. Namely, has the patient died of the disease at 10 years, or are they still living?
The authors of the paper wrote at the time, “The 10-year interval was chosen because death from melanoma beyond 10 years is uncommon.”
Obviously, Senator McCain is still very much alive and kicking. So what does that mean in terms of the 24% odds? What about the future?
The author of the Lancet letter cites another paper to estimate Senator McCain’s future risk of death from melanoma.
He writes, “With regard to future risk, Kolmel and colleagues have shown that for male patients with thickness T3 melanoma the increased mortality associated with such tumours is relatively constant and remains so for 15 years from diagnosis.”
The paper referred to does have a chart that shows a relatively flat line for annual recurrence, implying that recurrence is equally distributed over a 15 year time period.
However—and this is difficult to understand—the percentage risk of recurrence is a percentage of a declining population of patients who have not already recurred.
In simpler terms, if you have 100 patients in year one, and 15% recur then the next year you have 15% recurrence rate in only 85 patients, and so on. So the rate may be constant, but the number of patients (and consequently the number that will recur) is declining over time.
The author also missed the survival curve which clearly shows that an overwhelming number of deaths from “T3” melanomas in this German study occurred before 96 months, which is where the Senator fits into this graph.
In fact, when you measure the risk of death from melanoma from about 96 months to about 146 months (the length of time from the election to the completion of a first term in relation to Senator McCain’s diagnosis in 2000), another graph shows a decline in survival of a couple of percentage points over that same 4+ year time frame.
And this is old data, which doesn’t include treatment advances, doesn’t consider the absence of regional lymph node surgery, and doesn’t include the fact that within this study over several time periods the survival of patients with the same characteristics improved significantly.
And there are more data sources.
SEER, which is a nationwide cancer registry supported by organizations including the National Cancer Institute and the Centers for Disease Control and Prevention shows clearly that most deaths from melanoma in white males diagnosed between the ages of 65 and 74 and measured over 16 years from 1988 through 2004 occur early after diagnosis. Few deaths occurred many years after diagnosis (although this includes “all comers” with varying melanoma characteristics). The actual survival percentage for this group is 87.30% at 8 years and 87.01% at 10 years.
Finally, another paper published in the journal Cancer in 2002 looked at the relationship between sex, location of the melanoma, thickness, and the presence or absence of ulceration.
Assuming a non-ulcerated lesion on the face in a male between 2 and 3 mm thick, the cured fraction is between 35.8 and 44.5%, the median survival is between 5.4 and 6.1 years, the assumed percentage cured at 10 years is between 70 and 74%.
However, the authors make a very interesting, important and what is at first glance illogical statement: it is the patients with thin melanomas (the Senator’s was considered a thicker melanoma) that have the higher percentage of late recurrences. For patients with thicker lesions, although still at some risk of recurrence, most of the recurrences in that group occur closer to the time of initial diagnosis.
So, if you have a less favorable melanoma, the longer you live the more likely you are to do well. It is a situation of what I call “diminishing probabilities” that your disease will recur.
This same paper also points out that “As survival increases, the prognosis tends to equalize among patients with thick lesions and patients with thin lesions.” The authors continue their comments to support the observation that the longer a patient with melanoma survives, the percentage expectation of further survival also continues to increase.
In simpler words, with melanoma and a relatively poor prognostic outlook, the longer you live, the more likely you are to have been cured of this disease.
I could go on with more statistics, but I think you get the point.
Cancer of any type is an unwelcome and dangerous disease. It is a fact of our lives.
Senator McCain has had several melanomas, one of which in particular was of concern. Because of that concern, the surgeons did extensive surgery at the time of diagnosis and found no evidence of lymph node involvement. That factor isn’t even included in any of these statistics, and what evidence we do have suggests that puts him in an even more favorable category.
But what the data does not support, in my opinion, is a statement that he has a 6 or 12% chance of dying every year. That is simply not borne out by the evidence.
To make such a statement in a major medical journal at this time in the campaign raises concerns for me and others. Not that the question is not legitimate—it is. But the timing is suspect and the chance to set the record straight is limited.
I expect higher standards from our respected medical journals. These types of political intercessions have occurred in the past with other highly regarded research publications, but I will defer that discussion for another day.
For the present, we need to understand what the evidence shows as opposed to turning it inappropriately into a tool for a momentary political advantage.
I know that I am writing this particular blog about a difficult and potentially sensitive subject.
I want to affirm for the record that I am not a vocal supporter of either candidate, and have made no contributions to either candidate, either party or any campaign-related committee or organization in support of anyone’s Presidential campaign. In addition, our organization and our employees are prohibited from engaging in any political activity related to our work for the American Cancer Society.
Finally, the opinions and comments contained in this blog are mine and mine alone and do not represent the position of the American Cancer Society on this matter.