Much of the confusion surrounding the benefits of
screening comes from interpreting the statistics that are often used to
describe the results of screening studies. An improvement in survival—how long
a person lives after a cancer diagnosis—among people who have undergone a
cancer screening test is often taken to imply that the test saves lives.
Indeed the interpretation is critical but even more
importantly is the question for which the statistics reflect an answer. Let me
address this in two ways; first by examining her diagrams and second by
examining some cancer specifics.
First, her examples. She provides two cases.
The first case is a demonstration that by diagnosing the
cancer early one obtains an improved 5 year survival but no change in time of
death. Consider the case shown below where she assumes the following. A patient
has lung cancer and it commences at some unspecified time and the patient dies
at 70. Now assume that by some unspecified but reliable test we can identify it
at say 60 years of age and act in some manner but that despite the actions and
early diagnosis the patient dies at 70. She contends we see a 100% 5 year
survival. True, but. Then assume we never did anything until some massive event
occurred at 67 and we then diagnosis the cancer and take some unspecified
actions. Then we would have a 0% 5 year survival.
Now what is wrong here? First, lung cancer is generally very
aggressive so that any chance of even a three year survival is low. Indeed if
there were a 10 year survival then that itself would have been a success. In fact
if diagnosed at 60, by whatever means, and treated by whatever means, more than
likely if untreated the patient would have died of lung cancer much earlier.
The fault here is that there is an assumption that the two
cases are pari passu, equal in all ways but the early diagnosis. In fact I
would argue we are comparing apples and oranges.
Now for the second case. Here she assumes that we have a
progressive and a non-progressive form of some cancer. The usual victim chose
especially by women is prostate cancer. So let us assume that. We then look at
two cases. First with no screening. Somehow there is no treatment and the
result is 400 dead and 600 alive. The protocol of diagnosis and treatment is
left unstated but one can assume that the patient presents say with an
inability to urinate or sever bone pain. Namely with no screening the patient
waits until the symptoms are obvious and compelling.
Now the second case she uses to demonstrate bias is that if
we screen, and that for every 3000 people screened who have the disease as a
result of screening, 2000 have an indolent form, which we cannot ascertain at time
of diagnosis, and 1000 still have the progressive form. Now she argues that
using this erroneous method we have a false survival rate of 80% rather than
the “true” rate of 40%.
Let me quote from the Bulletin:
"I had a brilliant oncologist say to me, 'Don, you
have to understand: 20 years ago, before mammography, I'd see a patient with
breast cancer, and 5 years later she was dead. Now, I see breast cancer
patients, and 15 years later they're still coming back, they haven't recurred;
it's obvious that screening has done wonders,'" he recounted. "And I
had to say no—that biases could completely explain the difference between the
two [groups of patients]."
There is a problem here. If the oncologist still sees
patients after 15 years then somehow we have managed to accomplish something.
After all in prior days the patient was seen at the point of massive tumor load
and significant metastasis. We again are comparing apples to oranges.
Now let us step aside and consider three cancers and the
screening issues.
1. Melanoma: Anyone familiar with melanoma knows that
screening does work. If we waited for the patients to come with a bleeding
lesion then most likely we would have a greater mortality rate. There is the
question of increased incidence and its relationship to increased screening,
but melanoma is one of those cancers that just have no indolent form. It is
plain and simple a killer and one can deduce that the increased incidence is
due to increased exogenous factors such as sun exposure, just look at
Australia. Now if we were to screen, especially those of increased risk (family
history, number nevi, sun exposure etc) using dermoscopy, and remove promptly
and effectively all suspect lesions, then it can be argued that we can reduce
the mortality substantially. Not just 5 year survival, but actual mortality due
to that specific melanoma.
2. Prostate: This is often the hot potato of screening. The
reason is, the opposition argues, that if biopsy is required, that it is
uncomfortable and there may be some limited morbidity.
The author states:
The extreme example of length bias is overdiagnosis,
where a slow-growing cancer found by screening never would have caused harm or
required treatment during a patient's lifetime. Because of overdiagnosis, the
number of cancers found at an earlier stage is also an inaccurate measure of whether
a screening test can save lives. (See the graphic on the left for further
explanation.)
The effects of overdiagnosis are usually not as extreme
in real life as in the worst-case scenario shown in the graphic; many cancers
detected by screening tests do need to be treated. But some do not. For
example, recent studies have estimated that 15 to 25 percent of screen-detected
breast cancers and 20 to 70 percent of screen-detected prostate cancers are
overdiagnosed.
The problem, however, is that we do not know the slow
growing from the virulent forms. We do not have genetic markers that tell is
that a Gleason 6 will become metastatic in 6 weeks while the Gleason 8 is going
nowhere. This is the fatal flaw in her second analysis. It assumes we know
indolent from aggressive, we just do not, until after the fact. Thus we treat
all as aggressive, which albeit costly may be in the end efficacious to saving
lives. Yet again we let the decision be an informed patient decision.
3. Colon: The question here is; what of colonoscopies? Clearly
here we have often slowly growing tumors, starting with adenomas and slowly
developing into invasive cancers. Removal of adenomas is an almost certain guarantee
of non-progression to a cancer. The data seem to demonstrate a saving of lives.
The procedure is invasive, and at times costly, with small but existing
morbidity factors. Should we ban this also?
Now the issue is; what should be the proper questions?
Namely, should we continue to do 5 year survival? More importantly should we
even start down the road of denying efficacy if we do not have enough
information? Again consider prostate cancer. We do not know how to tell
aggressive from indolent, so should we just stop PSA testing? PSA testing helps
for the aggressive group, albeit a small but unidentifiable sample.
I suggest stepping back and looking at the questions. The
author in her presentation I believe makes a strong argument for it, not by
what she understood and said, but what was clearly not understood and left unsaid.
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