S.E. Nissen, K. Wolski,
"Effect of rosiglitazone on
the risk of myocardial
infarction and death from
cardiovascular causes,"
New Engl. J. Med.,
356(24): 2457-71, 14 June
2007. [Cleveland Clinic,
OH] *178DR
53
1
2
J. Yu, et al.,
"Induced pluripotent
stem
cell lines derived
from human somatic
cells,"
Science,
318(5858): 1917-20, 21
December 2007. [Genome
Ctr. Wisconsin,
Madison; U. Wisconsin,
Madison] *243HE
53
†
3
R.J. Motzer, et
al., "Sunitinib versus
interferon alfa in
metastatic renal-cell
carcinoma," New Engl.
J. Med., 356(2):
115-24, 11 January 2007.
[10 institutions worldwide]
*124NE
49
4
4
L.J. Scott, et
al., "A genome-wide
association study of type 2
diabetes in Finns
detects multiple
susceptibility variants,"
Science,
316(5829): 1341-5, 1 June
2007. [12 U.S. and Finland
institutions] *173PS
49
5
5
R. Sladek, et al.,
"A genome-wide association
study identifies novel risk
loci for type 2 diabetes,"
Nature, 445(7130):
881-5, 22 February 2007.
[14 institutions worldwide]
*138CR
48
2
6
P.J. Rosenfeld, et
al., "Ranibizumab for
neovascular age-related
macular degeneration,"
New Engl. J. Med.,
355(14): 1419-31, 5 October
2006. [5 U.S. institutions]
*090UA
46
†
7
E. Zeggini, et
al., "Replication of
genome-wide association
signals in UK samples
reveals risk loci for type
2 diabetes,"
Science,
316(5829): 1336-41, 1 June
2007. [10 U.K.
institutions] *173PS
45
7
8
B. Escudier, et
al., "Sorafenib in
advanced clear-cell
renal-cell carcinoma,"
New Engl. J. Med.,
356(2): 125-34, 11 January
2007. [15 institutions
worldwide] *124NE
41
3
9
T. Sjoblom, et
al., "The consensus
coding sequences of human
breast
and colorectal
cancers,"
Science,
314(5797): 268-74, 13
October 2006. [11 U.S.
institutions] *093TV
40
†
10
G. Hudes, et al.,
"Temsirolimus, interferon
alpha, or both for advanced
renal-cell carcinoma,"
New Engl. J. Med.,
356(22): 2271-81, 31 May
2007. [17 institutions
worldwide] *172PO
The principles of medical screening were set out 40 years
ago in a World Health Organization paper (J.M.G. Wilson, G.
Jungner, WHO Chron., 22[11]: 473, 1968). They have
been played around with over the years. For instance, these
days you will find more emphasis on randomized trial evidence,
and the health economics criteria may be stricter, but
essentially the 10 principles have stood the test of time.
Sadly, they have not always been adhered to, and screening
often leads to lively debate. Cancer screening is no exception.
Screening for breast cancer, and tests for cancer of the
uterine cervix, are public-health policy in many countries, but
neither has been free from controversy. Nor has prostate cancer
screening. On lung cancer screening, the U.S. Preventive
Services Task Force in 2004 found "evidence insufficient to
recommend for or against" testing symptom-free individuals by
any of the three techniques being explored (computerized
tomography [CT], sputum cytology, and conventional chest
radiography). A paper that is currently below the Top Ten but
sure to rise higher in the
Thomson
Reuters citation rankings makes an important if not
decisive contribution (at #18, The International Early Lung
Cancer Action Program [IELCA] Investigators, New Engl. J.
Med., 355 [17]: 1763-71, 2006; total cites 154, latest
bimonthly citation count 29).
The Early Lung Cancer Action Program published its first major
finding, which has since been confirmed, in 2004. It appeared
that more than 80% of individuals who had had lung cancer
diagnosed as a result of a baseline or follow-up spiral CT scan
had clinical stage I disease (early), the only stage at which
talk of cure is thought to be realistic. Participants were
symptom-free at the time of screening but were at risk because
they smoked (or were exposed passively to smoke) or were
occupationally at risk because of, for example, exposure to
asbestos. What happened later is the focus of paper #18.
Screening of 31,567 people resulted in a diagnosis of lung
cancer in 484, with an estimated lung-cancer-specific 10-year
survival rate of 80%. However, this figure rose to 92% for the
302 stage I patients who underwent lung resection within a
month of the diagnosis.
Good news, surely? Yes, but—which is where the criteria
come in. We cannot assume that a cancer detected in this way
will behave exactly the same as one presenting later on with
symptoms (a problem that complicates prostate cancer
screening). Any treatment given earlier than usual will have an
apparent benefit on survival; this is the lead-time bias.
Because smoking damages health in other ways, improved lung
cancer-specific survival may not tell the whole story, as
revealed in a modelling on data from the Mayo Clinic (P.M.
McMahon, et al., Radiology, 248[1]: 278-87,
2008). Other commentators emphasize the need for a control
group as well as unbiased outcome measures (H.G. Welch, et
al., Arch. Intern. Med., 167[21]: 2289-95, 2007).
The U.S. task force will want to look again at the case for
this screening, but with so many other studies in the pipeline
it may be as well to wait. The U.S.
Lung Screening Trial is comparing spiral
CT with chest radiography. Then in Europe there is the
Netherlands-Louvain Lung Cancer Screening Study (R.J. van
Klaveren, et al., Ned. Tijdschr.
Geneeskd., 152[4], 225-35, 2007) and the Cancer
Research UK funded Lung-SEARCH study of spiral CT and
fluorescence bronchoscopy in patients at risk by virtue of
having chronic obstructive pulmonary disease. Randomized
controlled trials of screening, especially in large numbers
of people who do not think of themselves as patients, are
difficult to carry out and interpret, and translating
results into public policy is difficult too. Paper #18
usefully fuels the debate without resolving
it.
A former deputy editor of The Lancet, Mr.
David W. Sharp, M.A. (Cambridge), is a freelance writer living
in Minchinhampton, Gloucestershire, U.K.
Keywords: lung cancer, cancer screening, Early Lung Cancer
Action Program, spiral computed tomography, spiral CT,
Lung-SEARCH.