DURHAM, N.C.-The gusto for screening high-risk patients for
lung cancer with low-dose spiral CT may be running roughshod over the
confusing and scant evidence of potential significant
benefit.
So conclude Duke radiologist Edward F. Patz Jr. and
colleagues in a review article in the Nov. 30 New England Journal of
Medicine. They argued that though smaller lung lesions may be detected with
the new technology, there’s no reliable evidence that smaller is more
curable.
In what amounted to a pointed editorial, they
pleaded with the clinical community to resist "public and political
pressure"-stemming from low-dose CT prevalence-screening data-to change
clinical practice hurriedly. In particular, they urged that any idea of mass
lung-cancer screening before careful trials are done should be put on
hold.
"There should be no compromise or shortcuts in the rigorous
scientific process required to determine whether this practice is
justified," they urged.
They warned that all too often
in recent years clinicians have been so seduced by rosy early studies that
they took experimental procedures into standard practice prematurely. Only
later did randomized studies reveal no benefit. As a prime example, they
cited the false promise of high-dose chemotherapy with stem-cell rescue
for metastatic breast cancer.
Much of the enthusiasm for
lung-cancer screening by low-dose spiral CT springs from the Early Lung
Cancer Action Project, spurred by Cornell’s Dr. Claudia I. Henschke and her
1999 interim paper in Lancet on 1,000 high-risk smokers over age 60. Her
study confirmed that low-dose CT was a sensitive screen for lung
nodules.
"The true clinical significance of the small [lung]
tumors found by screening is unknown, and their effect on mortality awaits
future investigations," the NEJM authors said. No convincing data, they
added, confirm that a primary 5-mm lung tumor has a significantly better
prognosis than a 10-mm tumor or even a 30-mm tumor.
They
cited a study of 510 node-negative patients by Dr. Patz and colleagues,
published in Chest this year, showing no outcome difference between patients
with 3-mm nodules and those with 1-mm masses.
"In fact,
clinical studies have confirmed that patients with small tumors can harbor
malignant cells in normal-appearing lymph nodes that are detectable only by
immunohistochemical or reverse- transcriptase PCR assays," they
said.
What’s more, they noted, low-dose CT detects an
indeterminate nodule in 23% of all screened patients. "The majority should
be benign, but evaluation of all those nodules is not a trivial problem.
This could create a very expensive clinical quagmire."
The National Cancer Institute, which has been cautious in its approach
to low-dose CT screening, is running a yearlong study with 3,000 current and
former smokers to see whether a randomized trial is feasible. According to
the NCI, about half of the hospitals in the United States own spiral-CT
units, and some institutions are advertising the scans aggressively to
smokers and ex-smokers for the early detection of lung cancer.
If NCI decides a randomized trial is feasible, it plans a study
of tens of thousands of participants that will take at least five years.
It will have the statistical power to detect a 20% mortality
reduction.
