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Sentinel
Node Biopsy - Ready for Prime Time? Anna Coppinger, 61, a school
cafeteria worker from Hingham, lies waiting outside the operating room
at South Shore Hospital in Weymouth, chatting with her husband and
daughters - and wincing whenever she jostled the needle that had been
placed in her left breast several hours earlier to guide surgeons to the
exact spot where her tumor lay. As
she liese there, a radioactive substance called technetium-99m sulfur
colloid, injected earlier, is seeping through the lymph ducts in her
breast toward lymph nodes in her armpit. Like
a growing number of people with cancer, Coppinger was about to undergo a
relatively new - and still-controversial - procedure called sentinel
node biopsy. Instead
of removing 10 to 20 lymph nodes in the armpit to check for signs of
cancer, Coppinger’s surgeon, Dr. Suniti Nimbkar, is planning to remove
just the first, or “sentinel,” node into which cancer cells were
most likely to have spread. If that node turns out to contain cancer, Coppinger will have another operation to remove the rest of her armpit
lymph nodes. But if it’s clean, she’ll get no further node surgery. Ever
since doctors began experimenting with sentinel node surgery in melanoma
patients a decade ago, the technique has “caught on like wildfire with
most surgical oncologists,” says Dr. Kenneth Tanabe, chief of surgical
oncology at Massachusetts General Hospital. Today,
this state-of-the-art technique is well-accepted for melanoma, and is
being studied for a number of other malignancies, including colon
cancer. But perhaps its most controversial application is in women with
breast cancer. The National Cancer Institute insists the procedure
should be considered “investigational” until the results of two
major studies, now underway, are available. But
around the country, surgeons like Nimbkar are already switching to the
new procedure, convinced that there is no need to wait. The
argument in favor is clearcut. Many solid tumors have been shown to
“drain,” or shed cancer cells, in an organized pattern, first to the
nearest lymphatic ducts and nodes, then to more distant ones, although
cancers sometimes “skip”
directly to distant ones. (The lymphatic system is part of the body’s
immune defense system. Cancer can also spread directly through blood
vessels.) This
means that taking out only the sentinel node could be just as reliable a
way to tell if cancer has spread as more drastic node surgery. Indeed,
two reviews published in 1999 and 2000 suggest that in breast cancer
patients, if the sentinel
is negative, the other armpit nodes will also be negative 95 percent of
the time. If the sentinel node is positive, there’s a 25 to 50
percent chance that the other armpit nodes will be positive. Sentinel
node biopsy clearly causes less pain. And it avoids many of the
complications of the full nodal surgery, which more than 80 percent of
women suffer. These range from temporary discomfort to numbness,
persistent burning sensations, infections, limited shoulder mobility and
more rarely, lymphedema, in which the arm can become chronically swollen
and prone to infection. But
a key question looms: Does taking out all the armpit lymph nodes make a
difference in long-term survival, or is the outcome be the same if only
the sentinel nodes are removed? Historically,
one of the main reasons that surgeons removed all the lymph nodes in the
armpit of a woman with breast cancer was to get rid of any possible
traces of cancer, says Dr. David Krag, the lead researcher for NCI’s
study in Vermont and professor of surgery at the University of Vermont
Cancer Center in Burlington. But
a government-sponsored study nearly 20 years ago began to challenge that
notion. It looked at women with breast cancer who had all their armpit
nodes removed and those who didn’t and could not find any “survival difference,” says Dr. Jeffrey Abrams, senior
investigator in the division of cancer treatment and diagnosis at the
NCI. Indeed,
“there is no firm evidence that removing involved lymph nodes improves
survival, even though it is standard practice,” the NCI notes on its
website (http://cancer.gov)
“Randomized studies suggest that lymph node removal may not improve
survival, although it is valuable in determining the stage of the
cancer. Sentinel node biopsy can be used to determine stage, so that may
be all that is necessary, even in node-positive women.” On
the other hand, the 20-year old American study that showed no survival
difference did not have enough patients to detect differences of less
than 10 percent in survival. Moreover, when data from this American
study are lumped together with data from five studies from outside the
US, the overall picture suggests that women who have full lymph node
dissection do have a five percent survival advantage over those who
don’t. In
other words, leaving cancerous nodes in the body does appear to be
“dangerous for survival,” Krag says. In
Krag’s own study, 5,400 women will be randomized to get sentinel node
biopsy plus a full armpit node dissection, or to sentinel node biopsy
only. Those who get the full dissection then go on to get whatever
subsequent treatment – chemotherapy or radiation – doctors deem
best. Among
those who get only sentinel node biopsy, if there is no sign of
spreading cancer, there is no further no surgery, although, like the
first group, they get whatever chemotherapy or radiation they need. If
there are signs of spreading cancer, those women get a full armpit node
dissection, as well as appropriate further therapy. “Until
you prove the ultimate survival is the same, you haven’t proved that
sentinel node biopsy can replace complete removal of all the underarm
lymph nodes,” says Abrams of NCI. Krag’s
study will also try to determine whether full armpit node dissection
decreases the odds of recurrence of cancer in the armpit, and will
compare the value of sentinel node biopsy versus full dissection as a
way of staging patients, or classifying them into categories to
determine their subsequent treatment. The
other major study is being led by Dr. Armando Giuliano, chief of
surgical oncology at the John Wayne Cancer Institute in Santa Monica,
CA. In
his study, which is designed to include 7,600 women with breast cancer,
Giuliano’s team will give all the women a sentinel node biopsy. Women
with negative sentinel nodes will receive whatever further therapy
doctors think best. Women
with positive sentinel nodes - expected to number about 1900 -
will then be randomized to full armpit node dissection or no
further node surgery or radiation. The idea is to see whether there is
any therapeutic value to removing all the lymph nodes. But the prospect
of leaving cancerous nodes in place is proving a tough sell, Giuliano
says, because many women do not want to take a chance on leaving lymph
nodes in if there are any signs of cancer.
Both
Giuliano and Krag will also use a new test to try to determine whether
women whose sentinel nodes are negative may nonetheless have
“micrometastases”– tiny traces of usually-undetectable cancer. Normally,
scientists examine lymph nodes with a simple test dubbed “H&E,”
for hematoxylin and eosin, colored stains that make all cells visible
and allow pathologists to see which cells might be cancerous. The
new technique uses IHC, or immunohistochemistry, which involves
antibodies that stain only epithelial cells. A healthy lymph node
usually contains no epithelial cells. But cancer cells are epithelial
cells, so a node that contains even a few cancerous cells will stain
positive. The IHC
technique, only done currently if there is ambiguity on the H and E
test, can detect even one or two cancer cells. At
South Shore Hospital, Coppinger’s sentinel lymph node surgery takes
less than an hour. With
Coppinger under general anesthesia, Nimbkar slips a sterile covering
over a special wand hooked to a geiger counter on a table. By
now, the radioactive substance (technitium sulfur colloid)
that was injected into Coppinger’s breast earlier has migrated
to her lymph nodes. Sure enough, as Nimbkar slides the wand over
Coppinger’s armpit, the geiger counter squawks as Nimbkar finds a
“hot spot.” “This
is just what you hope for,” says Nimbkar, as she makes a 1-inch
incision just above the hot spot. Slowly, she dissects away the top
layers of fat, probing with her finger until she locates the first node.
Carefully, Nimbkar cuts out the node, then slips the wand back into
Coppinger’s armpit. The geiger counter now registers almost nothing, a
strong sign that there are no other nodes in the area. “I
think we’re good,” she says, beginning to sew up the small armpit
incision before moving on to do a lumpectomy to remove the tumor in
Coppinger’s breast. A
week later, Coppinger says she’s “doing terrific – I’m going to
play baseball.” Her
lab results turned out fine, too. Her node was negative, which means
it’s very unlikely that cancer has spread to any other nodes. Judy Foreman’s column appears every other week in Health-Science. Her past columns are available on Boston.com and www.myhealthsense.com. Her email address is foreman@globe.com
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