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.