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Dr. Jack West is a medical oncologist and thoracic oncology specialist, and Executive Director of Employer Services at the City of Hope Comprehensive Cancer Center in Duarte, CA.

Lung Cancer Screening, Part II: The Downside
Thu, 01/25/2007 - 19:02
Howard (Jack) West, MD, Associate Clinical Professor, Medical Oncology, Executive Director, Employer Services, Founder, President and CEO of GRACE

The topic of lung cancer screening is a very charged one, with most people, patients and physicians alike, having a strong opinion, either for or against. This is also an area in which there can be suspicion that any argument against screening is due to a financial calculation in which saving people from lung cancer isn't worth the cost of imaging. Any screening discussion also entails a consideration of cost, financial and other, vs. benefit, but here I'll focus on the issues related to the possible shortcomings of lung cancer screening in terms other than cost.

First, while CT screening can detect lung cancers, it also detects lots of little nodules that turn out to not be cancer. In fact, only a small proportion of nodules on CT are actually lung cancers, and nearly half of the patients involved in some screening trials have nodules identified. Those people who are told there is a nodule to follow now are subject to the anxiety of knowing they have a visible abnormality that is unlikely to be but possibly could be cancer. I have seen a few patients in my clinic who don't have a cancer diagnosis but have a nodule that is being followed that appears unlikely to be cancer but which leaves them sleeping with one eye open all the time, worried about the possibility that they have lung cancer. There is also the risk that they will need to go through invasive procedures, ranging from a bronchoscopy or CT-guided biopsy to a video-assisted thoracoscopic surgery or even a full thoracotomy (open lung surgery) to get tissue and obtain a definitive diagnosis. In one series (abstract here), twenty percent of the thoracotomies were done for what turned out to be a benign cause. Of course, there are complications that may occur with an invasive procedure, such as a collapsed lung (pneumothorax), pain, risk of infection, and many other problems, even including death. Fortunately, that's unlikely, but the mortality risk (i.e., risk of dying) from a lobectomy and mediastinal staging is in the 1-3% range, not zero. And it's especially tragic if you're chasing down a diagnosis that wasn't actually cancer.

The other concern is that even detecting cancers may not actually translate to improving survival. To have screening be successful, you need to have a disease that is asymptomatic, can reliably be detected while there are no symptoms, and that can be effectively treated after early detection to improve the survival from the disease. But there are several potential biases that can lead us to think a screening test is more effective than it really is (figures below are all stolen borrowed from an older but very good New England Journal of Medicine review with reference here). For instance, there is lead time bias, which means that you find out something earlier but don't actually change the outcome, and therefore the apparent survival after diagnosis is longer without better survival (the circle with the dot inside represents the screened person with a cancer):

Lead TIme Bias Figure (click to enlarge)

This would be like being told that a meteor is going to hit earth and destroy the planet on January 5, 2009. Not much help to know if we can't change the outcome, but instead just learn the bad news sooner.

Another potential problem is length-time bias, which is that screening is most likely to pick up less aggressive cancers, because they have a longer interval of being visible on scans while remaining asymptomatic. The more aggressive cancers grow quickly enough that a yearly CT scan would have less opportunity to detect them before they cause symptoms:

Length-Time Bias Figure

The extreme version of this can cause something called overdiagnosis bias, which is when a cancer can be so slowly moving that it doesn't really impact survival, but screening allows you to find these non-threatening cancers and show that survival is remarkably good, but in the control group these people would never have had symptoms, never have been diagnosed with cancer, and would have died of unrelated causes without ever knowing they had cancer:

Overdiagnosis figure

If that concept seems familiar, it may be because you read a similar sentiment I recently described in a post about the potential of overtreating indolent bronchioloalveolar carcinomas. I wasn't arguing against screening in that post. I was just saying that as someone who sees and treats a lot of BAC, I am seeing a significant fraction of these patients with a form of the disease that I'm concerned have such a slow moving cancer that it would never be a threat to their survival, and the treatment could be worse than the disease. That was me expressing my concern about overdiagnosis bias with BAC (although it can happen with other lung tumors, just less commonly), without using that terminology. And some publications have shown that screening studies have detected a significant number of tumors that have a remarkably slow doubling time (abstracts here and here), potentially taking years for a tumor of just a few millimeters to grow to 1.5 or 2 cm, and likely much, much longer to be a threat to survival.

One other issue is that even the advocates of screening aren't suggesting that never-smokers or patients under 40 be screened routinely, but I know that there are many never-smokers with lung cancer who feel that screening would have been remarkably beneficial for them. But once you start expanding a screening program to a broad population at much lower risk, it both dramatically increases the cost of a screening program and raises the likelihood that what you find will be something other than what you're looking for. So you end up spending way more money to cause far more anxiety, remove many more benign nodules with a risk for real complications, to find fewer and fewer real cancers. So even a CT screening process that the major proponents envision wouldn't detect the vast majority of the 20,000-25,000 never-smokers in the US who are diagnosed with lung cancer each year (or the 30-50% never-smokers in most recent series from Asia).

I'll conclude next time with some general comments of where we stand with screening in the US these days. But I'll just clarify one point here, which is that while I have mentioned some areas in this discussion that may be shortcomings of screening, the arguments in favor of screening that I described in my last post also have some clear validity. I am not attacking motherhood and apple pie here. I am not arguing for or against a formalized lung cancer screening program here, just trying to offer everyone an idea of the ways in which people are considering this complex and very polarizing topic.

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