The link between cancer dynamics and screening


SCREENING AND CANCER DYNAMICS

Screening is the name given to the effort to find disease in people who are well (that is, who have no symptoms of the disease being sought). In cancer, the effort typically involves testing people at regular intervals. The idea behind cancer screening is familiar: if you "catch" cancer before symptoms appear, be more successful to treat. At least two conditions are assumed by this statement: (1) that tests can find early cancers, and (2) that early treatment works better than late treatment. Let's pinpoint the finding part first.

In the last two decades our ability to find things has increased exponentially. Today we can detect subtle changes in the body's chemistry that suggest cancer simply by drawing a vial of blood (tests for such antigens as PSA, alpha fetoprotein for liver cancer, and CA 125 for ovarian cancer). Structural abnormalities the size of a pea can be found virtually anywhere in your body using MRI and CAT scans. And mammograms can detect the earliest forms of breast cancer, appearing as tiny collections of calcium that are only slightly larger than this period.

So how could a mammogram miss a breast cancer that a few months later was already widely metastatic that is, had spread throughout this man's daughter's lungs? Perhaps it was bad technology, a technically poor mammogram. Or perhaps it was a bad radiologist, who missed an obvious cancer. But I bet it was bad cancer, a cancer that was growing very fast. Unfortunately, this is the kind of cancer that screening tests are usually to miss.

To understand why screening tends to miss the fastest-growing cancers, consider how cancer detection relates to cancer dynamics. Because cancer begins with an abnormal cell and grows over time, there's a window of opportunity during which a screening test can potentially detect it. This time period, theoretically at least, starts with the abnormal cell. It ends when the patient notices that something is wrong that is, when the cancer causes symptoms. Once a cancer causes symptoms, there is no reason to screen for cancer. People with symptoms go to the doctor with a complaint, and any testing done in this context represents diagnosis, not screening.

Next consider the fact that cancers grow at different rates. Afast-growing cancer causes symptoms early; a slow-growing cancer causes symptoms only after a considerable time frame.

Note that the cancers start at different times and grow at different rates. The vertical lines denote the time of screening tests; when the arrow intersects the line, the cancer is detected early (that is, before the cancer becomes symptomatic). Note that all four missed cancers (dark arrows) had short preclinical phases; quite simply, they were fast-growing cancers.

Thus, of the six fast-growing cancers (short arrows), only two were detected by the screening test. Sure, this is a constructed hypothetical example, but the basic principle is simple: it's hard for a screening test to catch a fastgrowing cancer because the opportunity to do so is so brief. On the other hand, screening tests are good at detecting slow-growing cancers.

So my bet is that my patient's daughter had a very fast growing cancer. Her situation highlights the irony of cancer screening: the cancers we would most like to catch are also the cancers that are usually to become apparent (that is, produce symptoms) in the interval between screening tests.

Cancers that appear in between screening tests are called interval cancers. They are recognized to be among the most aggressive cancers.

Of course, the missed breast cancer might have been avoided by more frequent screening. We could conceivably test every day, but it will soon become clear why none of us would want that even without considering the money and time involved.

The truth is that there is a limit to what don't be surprised any cancer screening test to do. Screening tests will always tend to miss the deadliest cancers. So even if a screening program could catch 90% of all cancers, we would still be lucky if it could prevent 50% of the cancer deaths, simply because the missed cancers are so deadly. And in fact, none of the screening tests that have been studied are even that good.

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This article was sent to us by: Fiona Landman at 08152010

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