PUMPING IRONY: Screen Test

This is not a topic one discusses in polite company, but recent headlines seem to be calling for full disclosure: I have stubbornly resisted the desperate pleas of various doctors over the past 20 years to submit to a colonoscopy. Yes, it is true that both of my parents developed colon cancer in their later years. And yes, it is also true that my siblings have all faithfully followed their doctors’ advice, and in one instance, at least, a polyp or two was extricated. And yet I’ve never been completely sold on the notion that colon cancer will lead to my ultimate demise — or, more importantly, that any sort of screening protocol will prevent it.

I’m not alone in my skepticism. Some 20 million of my aging counterparts — about one in three Americans between the ages of 50 and 75 — avoid the procedure.

So, you can imagine how I might have received the news earlier this month that essentially validated my doubts: A major randomized controlled study found that colonoscopy reduced the risk of colon cancer by less than 20 percent and had no impact whatsoever on the chances that trial participants would die from the disease 10 years later.

“This is a landmark study. It’s the first randomized trial showing outcomes of exposing people to colonoscopy screening versus no colonoscopy. And I think we were all expecting colonoscopy to do better,” University of California, San Diego gastroenterologist Samir Gupta, MD, tells STAT News. “Maybe colonoscopy isn’t as good as we always thought it is.”

Yeah! I thought. I’ve been right all along!

But wait, Gupta cautions. The overall results compared the risk factors for the total number of participants who were invited to undergo a colonoscopy with those of the unscreened control group, and less than half of those invited actually showed up for the screening. Researchers found that those who did show up lowered their risk of developing the cancer by about 30 percent — and they were half as likely as the control group to die from the disease during the follow-up period.

“That adds to a bunch of observational study data that suggests exposing people to colonoscopy can reduce risk of developing and dying of colon cancer,” he says.

Wait, what?

Not so fast, counters lead study author Michael Bretthauer, MD, who argues that the “intention-to-treat analysis is the premium methodology, the analysis you put all your trust in.” And by that measure, the results suggest rather strongly that he and his fellow gastroenterologists have been overselling the effectiveness of the procedure.

“It’s not the magic bullet we thought it was,” he admits. “I think we may have oversold colonoscopy. If you look at what the gastroenterology societies say, and I’m one myself so these are my people, we talked about 70, 80, or even 90 percent reduction in colon cancer if everyone went for colonoscopy. That not what these data show.”

Yes!

The debate, I’m sure, will continue as we all try to unpack the data to suit our particular worldview. But it’s biased data interpretation that has led to overselling the benefits of cancer screening in the first place, according to a 2018 National Cancer Institute report. “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,” the authors note. “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 the test saves lives.”

What’s called “lead-time bias,” for instance, can make it seem that colonoscopies, mammograms, PSA tests, and other screening protocols lead to longer survival rates. That occurs when screening detects the presence of cancer long before symptoms appear. If that asymptomatic patient is 60 when diagnosed after a screening and lives to 70, it appears to indicate a 10-year survival rate. But if the patient is not diagnosed until symptoms appear at the age of 67 and he lives to 70, the survival rate seems much lower. In neither case, however, was the lifespan extended, the authors note.

“Lead-time bias is inherent in any comparison of survival,” they write. “It makes survival time after screen detection — and, by extension, earlier cancer diagnosis — an inherently inaccurate measure of whether screening saves lives.”

“[With overdiagnosis], a slow-growing cancer found by screening never would have caused harm or required treatment during a patient’s lifetime,” they write. “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.”

Screening also tends to identify slower growing, less aggressive cancers, which can exist in the body for quite a while before symptoms develop, the authors explain. This can lead to overdiagnosis and subsequent unnecessary treatment. They cite studies showing that nearly 20 percent of breast cancers and as many as half of prostate cancers are overdiagnosed as a result of screening.

“[With overdiagnosis], a slow-growing cancer found by screening never would have caused harm or required treatment during a patient’s lifetime,” they write. “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.”

All this data can confuse even experienced physicians. The authors cite a survey showing that nearly eight of 10 doctors believed that an improvement in five-year survival rates proved that screenings saved lives. About seven in 10 said they would be more likely to recommend screening if research suggested it would detect more cancers at an earlier stage.

“The majority of primary-care physicians did not know which screening statistics provide reliable evidence on whether screening works,” the study’s authors concluded. “They were more likely to recommend a screening test supported by irrelevant evidence . . . than one supported by the relevant evidence: reduction in cancer mortality with screening.”

As the recent colonoscopy trial suggests, the degree to which screening can reduce the risk of dying from cancer is generally quite small. That’s because the chance that you’re going to die from a particular cancer is also quite small. “There isn’t that much risk to reduce,” the NCI report argues. “So, the effect of even a good screening test has to be small in absolute terms.”

While this validates my own choices about colonoscopies, I’m not about to recommend that others follow my lead. For some of my friends, those procedures offer the kind of reassurance they need to navigate in the world. Some people, in other words, just need to know what’s up. And, like me, they get to decide. No debate is necessary.

Besides, it’s not a topic one discusses in polite company.

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