'Early' Detection of Cancer Needs to Be Even Earlier

I’ve spent the last few days talking to cancer researchers about why early detection doesn’t reduce mortality from this disease much or at all, as recent studies of the PSA test for prostate cancer concluded (the New England Journal of Medicine has made the two papers available here and here). That conclusion, sadly, has been a frequent refrain, as I’ll discuss in next week’s magazine column.

An interesting paper in the April issue of Nature Reviews Cancer (part of a package of articles on cancer metastasis that Nature is making freely available for three month, here) suggests that in addition to whatever is going on with the primary tumor to thwart the value of early detection, the process of metastasis is also undermining the effectiveness of early detection. Cells might leave the primary tumor “much earlier in the course of disease than previously thought, even before the primary tumor is clinically detectable,” reports Nature.

The standard model of metastasis says that tumor cells migrate out of the primary tumor and head for far-flung parts of the body—often the bones, brain and liver—only when the primary tumor is fairly large. The idea is that a tumor's component cells need time to evolve characteristics that let them to invade other organs and grow there. But as Christoph Klein of the University of Regensburg in Germany argues, there is another possibility. Called the “parallel progression model,” it says that tumor cells head for distant sites when the primary tumor is still small. Only after they have landed in their new home do they develop the traits needed to survive and grow there.

Klein told me by email that “early dissemination is not identical to metastasis,” since tumor cells that head for the hills may fail to form a metastasis. “We frequently detect disseminated tumour cells (DTCs) in patients who will never develop metastasis,” he explained. “However, if we find DTCs, the risk for metastasis is higher.” The relevance of this to early detection is this: in many cases, malignant cells will migrate out of the primary tumor “before clinical detection,” he says. “Why tumor size is associated with metastasis is now open for discussion,” but the unhappy implication is that potentially metastatic cells will already be on the move before the primary tumor is detected or even detectable. In this case, “early” detection is still too late, since metastases account for some 90 percent of cancer deaths.

One silver lining in this cloud, says Klein, is that “if dissemination is early, we may be able to detect DTCs before we can detect the primary tumor, because we can find them in bone marrow samples or other samples [preferentially blood], before imaging techniques allow detection of the cancer. And I do believe that very early detection is almost as good as complete prevention.” Note the “very”: for early detection to decrease the risk of dying from the cancer, it apparently must occur even earlier than we thought—or than we can accomplish with current technology.