C a r d i o p u l m o n a r y I m a g i n g • R ev i ew

Kligerman and Abbott

New TNM Classification for Lung Cancer

Cardiopulmonary Imaging
Review
Downloaded from www.ajronline.org by 36.77.194.79 on 05/08/16 from IP address 36.77.194.79. Copyright ARRS. For personal use only; all rights reserved

FOCUS ON:

A Radiologic Review of the New

TNM Classification for Lung Cancer
Seth Kligerman1 OBJECTIVE. In 2009, a new TNM staging system was published by the International
Gerald Abbott 2 Union Against Cancer and the American Joint Committee on Cancer. The new edition will
encompass non–small cell lung cancer, small cell lung cancer, and bronchopulmonary car-
Kligerman S, Abbott G cinoids. This article will review many important changes that have been made in the revised
staging system.
CONCLUSION. It is important that radiologists learn the new system and understand
the reasons for the changes to provide more accurate clinical staging.

Keywords: International Association for the Study of
Lung Cancer (IASLC), lung cancer, staging, TNM
DOI:10.2214/AJR.09.3354
Received July 21, 2009; accepted after revision
September 1, 2009.
Presented at the 2009 annual meeting of the American
Roentgen Ray Society, Boston, MA. Winner of the
Silver Medal.
1
Department of Diagnostic Radiology, University of
Maryland Medical Center, 22 S Greene St., Rm. N2W78,
Baltimore, MD 21201. Address correspondence to
S. Kligerman (sethkligerman@hotmail.com).
2
Department of Radiology, Massachusetts General
Hospital and Harvard Medical School, Boston, MA.
CME
This article is available for CME credit.
See www.arrs.org for more information.
AJR 2010; 194:562–573
0361–803X/10/1943–562
© American Roentgen Ray Society
I
n the United States, lung cancer
remains the most common cause
of cancer-related death in both
men and women. In 2008, it was
estimated that lung cancer was the cause of
57% of cancer-related deaths, accounting for
more deaths than breast, prostate, colon, rec-
tal, and pancreatic cancers combined [1]. In
2009, the seventh edition of the TNM stag-
ing system for lung cancer was published by
the International Union Against Cancer and
the American Joint Committee on Cancer,
based on proposals from the International
Staging Project of the International Associa-
tion for the Study of Lung Cancer (IASLC).
In addition to non–small cell lung cancer
(NSCLC), the new classification system will
be used to stage both small cell lung cancer
(SCLC) and bronchopulmonary carcinoid
tumors. Many important revisions have been
made to the TNM classification of lung can-
cer, and it is important for the radiologist to
learn of these changes to provide more accu-
rate clinical staging.
IASLC Population and Methodology
Between 1990 and 2000, the data from
100,869 cases of newly diagnosed primary
lung cancer were submitted to the Cancer
Research and Biostatistics (CRAB) office.
The data originated from 46 different data-
bases collected across 19 countries in North
America, Asia, Europe, and Australia. Of
these 100,869 patients, 19,854 were excluded
because of unknown histology, incomplete
survival data, incomplete stage information,
recurrent disease, or data collected outside of
the study period [2]. Less common lung neo-
plasms, such as carcinoid tumors and sarco-
mas, were also excluded. Of the remaining
81,105 eligible cases, 67,725 (83.5%) were
NSCLC and 13,290 (16.4%) were SCLC [3].
Of the 81,105 patients with primary lung can-
cer, 36% were treated with surgery alone, 11%
with radiotherapy alone, 21% with chemothera-
py alone, 23% with a combination of therapies,
and 9% were treated supportively [4].
Two primary methods of lung cancer stag-
ing are available: clinical staging and patho-
logic staging. In clinical staging, information
is provided by noninvasive or minimally in-
vasive techniques, such as physical examina-
tion, radiologic examination, endoscopic ul-
trasound, bronchoscopy, mediastinoscopy,
and thoracoscopy. In pathologic staging, in-
formation obtained from clinical staging is
combined with findings from both the inva-
sive surgical procedure and the pathologic
evaluation of the excised tissue [5]. Clinical
staging is important and can help to deter-
mine the next appropriate step in therapy,
such as the decision to proceed with patho-
logic staging. However, direct comparison
between the two systems is difficult because
selection bias often leads to improved out-
comes in those who obtain pathologic stag-
ing versus those who are only staged clini-
cally [4]. It is important to remember that
pathologic staging remains the reference
standard because the overall level of agree-
ment between the two systems only ranges
from 35% to 55% [5]. Of the 67,725 cases

562 AJR:194, March 2010

 New TNM Classification for Lung Cancer

of NSCLC in the IASLC study, clinical stag-
ing was available in 53,640 cases, whereas
pathologic staging was available in 33,933
cases [4, 6]. Overlap of data occurred when
patients had both clinical and pathologic
staging data available.
Downloaded from www.ajronline.org by 36.77.194.79 on 05/08/16 from IP address 36.77.194.79. Copyright ARRS. For personal use only; all rights reserved
Using this large data set, survival statistics
were calculated on the basis of the prognostic
impact of various factors, including the T, N,
and M designations as well as the final stage.
Adjustments were made for cell type, sex, age,
and the region where the data were collected.
All data were internally validated by origin and
type of database. Additionally, external valida-
tion was obtained by testing the results against
data collected from 1990 to 2002 in the Na-
tional Cancer Institute’s Surveillance, Epide-
miology, and End Results (SEER) database.

TABLE 1:  Seventh Edition of the TNM Classification of Lung Cancer Compared With the Sixth Edition
Prior System New System Five-Year
Tumor Designation (Sixth Edition) (Seventh Edition) Survival Rate (%)
Size
≤ 2 cm T1 T1aa 77d
> 2 but ≤ 3 cm T1 T1ba 71d
> 3 but ≤ 5 cm T2 T2aa 58d
> 5 but ≤ 7 cm T2 T2ba 49d
> 7 cm T2 T3a 35d
Pleural or pericardial invasion
Visceral pleura T2 T2ab or T2bc NAe
Parietal pleura T3 T3 NAe
Mediastinal pleura T3 T3 NAe
Parietal pericardium T3 T3 NAe
Central airway invasion
Tumor extending into mainstem bronchus > 2 cm from carina T2 T2ab or T2bc NAe
Tumor extending into mainstem bronchus ≤ 2 cm from carina T3 T3 NAe
Tumor extending to carina T4 T4 NAe
Lung atelectasis
Tumor causing atelectasis of less than entire lung T2 T2ab or T2bc NAe
Tumor causing atelectasis of entire lung T3 T3 NAe
Soft tissue invasion
Chest wall and superior sulcus T3 T3 NAe
Diaphragm T3 T3 NAe
Mediastinum T4 T4 NAe
Heart or great vessels T4 T4 NAe
Trachea T4 T4 NAe
Esophagus T4 T4 NAe
Osseous invasion
Rib T3 T3 NAe
Vertebral body T4 T4 NAe
Nerve invasion
Phrenic nerve T3 T3 NAe
Recurrent laryngeal nerve T4 T4 NAe
Note—Cells in bold indicate a change in the designation from the sixth edition. NA indicates not applicable.
aT designation is listed for tumors completely surrounded by lung. Designation can increase depending on presence and extent of invasion.
bT2a designation if tumor measures ≤ 5 cm in long-axis diameter.
cT2b designation if tumor measures > 5 cm but ≤ 7 cm in long-axis diameter.
dSurvival based on patients staged pathologically with complete resection of tumor (R0) and no nodal or extranodal metastatic disease (N0M0).
eIndividual survival statistics not calculated due to limited information. As a group, 5-year survival rate in patients pathologically staged with a T3 and T4 designation

(excluding those with tumors > 7 cm or satellite nodules), any R, any N, and M0 was 31% and 22%, respectively.
f Survival based on patients staged pathologically with complete or incomplete resection of tumor (any R), any nodal disease (any N), and M0.
gSurvival based on patients staged pathologically with any tumor designation (any T) and M0.
hSurvival based on patients staged clinically with any T and any N.

(Table 1 continues on next page)

AJR:194, March 2010 563

 Kligerman and Abbott

TABLE 1:  Seventh Edition of the TNM Classification of Lung Cancer Compared With the Sixth Edition (continued)
Prior System New System Five-Year
Tumor Designation (Sixth Edition) (Seventh Edition) Survival Rate (%)
Satellite nodules
Same lobe T4 T3 28 f
Same lung, different lobe M1 T4 22 f
Downloaded from www.ajronline.org by 36.77.194.79 on 05/08/16 from IP address 36.77.194.79. Copyright ARRS. For personal use only; all rights reserved

Lymph node designation

No lymphadenopathy N0 N0 56g
Ipsilateral, peripheral, or hilar–interlobar zone involvement N1 N1 38g
Ipsilateral upper, aorticopulmonary, lower, or subcarinal zone involvement N2 N2 22g
Supraclavicular or contralateral upper, aorticopulmonary, lower, hilar–interlobar, or peripheral zone N3 N3 6g
involvement
Metastatic disease designation
Contralateral lung metastases M1 M1a 3h
Pleural or pericardial dissemination T4 M1a 2h
Distant metastases M1 M1b 1h
Note—Cells in bold indicate a change in the designation from the sixth edition. NA indicates not applicable.
aT designation is listed for tumors completely surrounded by lung. Designation can increase depending on presence and extent of invasion.
bT2a designation if tumor measures ≤ 5 cm in long-axis diameter.
cT2b designation if tumor measures > 5 cm but ≤ 7 cm in long-axis diameter.
dSurvival based on patients staged pathologically with complete resection of tumor (R0) and no nodal or extranodal metastatic disease (N0M0).
eIndividual survival statistics not calculated due to limited information. As a group, 5-year survival rate in patients pathologically staged with a T3 and T4 designation

(excluding those with tumors > 7 cm or satellite nodules), any R, any N, and M0 was 31% and 22%, respectively.
f Survival based on patients staged pathologically with complete or incomplete resection of tumor (any R), any nodal disease (any N), and M0.
gSurvival based on patients staged pathologically with any tumor designation (any T) and M0.
hSurvival based on patients staged clinically with any T and any N.

T Designation T1b (Fig. 1) using the cut points of 2 and 3 optimized using cut points of 3, 5, and 7 cm.
The tumor (T) designation is determined cm, respectively. Tumors greater than 3 cm but less than or
by the size of the primary tumor as mea- Similar calculations were performed for equal to 5 cm had a 5-year survival of 58%.
sured in the long-axis diameter, extent of in- completely resected lung masses greater than Tumors greater than 5 cm but less than or
vasion of the primary tumor, and presence 3 cm in patients with pathologically staged equal to 7 cm had a 5-year survival of 49%
or absence of satellite nodules (Table 1). Of N0M0 disease, and survival differences were [7]. On the basis of these findings, the T2
67,725 cases of NSCLC initially included in
the IASLC database, 18,198 cases met the in-
clusion criteria for T designation analysis by
having accurate clinical or pathologic staging
and no metastatic disease. Using these cases,
survival statistics were calculated based on
the tumor size in patients who had undergone
pathologic staging and surgical resection of
the primary tumor. After surgical resection,
patients were classified as R0 if there was no
residual disease, R1 if microscopic residual
disease was present, or R2 if gross residual
disease was present. In patients with nodules
measuring 2 cm or less that were complete-
ly surrounded by lung or visceral pleura, in
the absence of nodal or extranodal metastat-
ic disease (N0M0) and with complete resec-
tion of tumor (R0), the 5-year survival was
77%. By comparison, patients with nodules A B
measuring greater than 2 cm but less than or Fig. 1—Changes to T1 designation for non–small cell lung carcinoma.
equal to 3 cm using the same criteria had a A, Axial CT image in 53-year-old man shows 1.6 × 1.5 cm adenocarcinoma in right upper lobe. Any tumor
5-year survival of 71% [7]. On the basis of measuring ≤ 2 cm in greatest diameter completely surrounded by lung or visceral pleura is now classified as
T1a.
these statistically significant findings, the T1 B, Axial CT image in 67-year-old woman with 2.2 × 1.5 cm adenocarcinoma in right upper lobe. Any tumor
designation has been divided into T1a and measuring > 2 cm to 3 cm and completely surrounded by lung or visceral pleura is now classified as T1b.

564 AJR:194, March 2010

 New TNM Classification for Lung Cancer

designation has been divided based on size:

tumors greater than 3 cm but less than or
equal to 5 cm are designated as T2a and tu-
mors greater than 5 cm but less than or equal
to 7 cm are designated as T2b (Fig. 2). For
tumors greater than 7 cm, 5-year survival was
35%, which was similar to the 41% 5-year
Downloaded from www.ajronline.org by 36.77.194.79 on 05/08/16 from IP address 36.77.194.79. Copyright ARRS. For personal use only; all rights reserved

survival in pathologically staged T3N0M0

tumors [7]. This led to the reclassification of
tumors greater than 7 cm as T3 (Fig. 3).
In the previous edition of the TNM stag-
ing system, tumors were designated as T2
based not only on size but also on the extent
of invasion. Tumors that invaded the visceral
pleura and extended into the mainstem bron-
chus but were greater than 2 cm from the
carina or caused atelectasis or postobstruc-
tive pneumonia without complete collapse
of an entire lung were also classified as T2. A B
However, alterations were necessary given Fig. 2—Changes to T2 designation for non–small cell lung carcinoma.
the subdivision of the T2 designation on the A, Axial CT scan in 72-year-old man shows 3.2 × 2.2 cm adenocarcinoma in right upper lobe. Any tumor > 3 cm
basis of size in the revised staging system. but ≤ 5 cm completely surrounded by lung is now classified as T2a.
B, Axial chest CT in 77-year-old man shows 5.5 × 5.2 cm squamous cell carcinoma in left upper lobe. Any tumor > 5 cm
Now any tumor less than or equal to 5 cm and ≤ 7 cm completely surrounded by lung or visceral pleura is now designated as T2b.
that meets any of the previously mentioned
invasion criteria will be designated as T2a.
Similarly, tumors greater than 5 cm but less
than or equal to 7 cm with the same degree of
invasion will be designated as T2b.
Accurate pathologic distinction between
degrees of visceral pleural invasion has been
shown to be an important prognostic indica-
tor of survival [8]. However, because the vis-
ceral pleura may have anywhere from four
to six histologic layers, the exact definition
of visceral pleural invasion has been debat-
ed. Therefore, the IASLC has defined vis-
ceral pleural invasion as invasion extending
through the elastic layer of the visceral pleu-
ra to the surface of the visceral pleura and
has recommended the use of elastin stains
for determination of this feature [8].
Important changes have also been made to
the T3 designation in the revised TNM clas-
sification. As stated previously, tumors great-
er than 7 cm in size are now designated as
T3. Additionally, patients with satellite nod- A B
ules in the same lobe, previously designated Fig. 3—Revisions to T3 designation for non–small cell lung carcinoma.
as T4, have been reclassified as T3 (Fig. 3). A, Axial chest CT in 78-year-old woman shows 8.3 × 6.4 cm large cell carcinoma in right upper lobe. Any tumor
measuring ≥ 7 cm is now designated at least as T3.
In patients with any pattern of nodal disease B, Curved coronal multiplanar reformation CT image in 71-year-old man shows small 1.6-cm adenocarcinoma in
(any N), M0, and with or without complete left upper lobe nodule with adjacent 8.0-mm satellite nodule. Presence of satellite nodule in same lobe has been
resection (any R), 5-year survival was 28%, redesignated as T3 in new staging system.
which is similar to the 31% for other T3 le-
sions using the same staging criteria [7]. diastinal pleura, or parietal pericardium (Fig. from the carina but not involving the carina
Many of the T3 designations will remain 4) are still classified as T3. Similarly, tumors or tumors of any size that cause atelectasis or
unchanged in the new revisions, primarily be- that invade the parietal pleura or chest wall, postobstructive pneumonia of an entire lung
cause their incidence was not high enough for including superior sulcus tumors or tumors (Fig. 4) will still be designated as T3.
accurate statistical survival analysis. Tumors that destroy ribs, are still classified as T3. Tu- Tumors with a malignant nodule in a differ-
that invade the diaphragm, phrenic nerve, me- mors in the mainstem bronchi less than 2 cm ent lobe but in the same lung were classified

AJR:194, March 2010 565

 Kligerman and Abbott

Fig. 4—T3 designation for non–small cell lung carcinoma.

A, Axial CT image in 47-year-old woman shows 6.7 × 4.2 cm mass in lingula with invasion into chest wall (white
arrow) and parietal pericardium (black arrow). Mass also invades into location of phrenic nerve (star), which
was confirmed at pathology.
B, Coronal chest CT image in 44-year-old woman shows 6.8 × 5.6 cm large cell carcinoma in right lower lobe
with invasion of diaphragm but no hepatic invasion on pathologic evaluation.
C, Coronal contrast-enhanced CT image in 66-year-old man shows complete atelectasis of left lung by 6.4 ×
3.5 cm left hilar mass (white arrow), which is difficult to differentiate from surrounding atelectatic lung. Mass
extends into mainstem bronchus (black arrow) 1.9 cm from carina but does not involve carina.
Downloaded from www.ajronline.org by 36.77.194.79 on 05/08/16 from IP address 36.77.194.79. Copyright ARRS. For personal use only; all rights reserved

A B C

Fig. 5—Revision to T4 designation for non–small
cell lung carcinoma. Coronal CT image in 64-year-
old man shows 5.2 × 4.5 cm large cell carcinoma in
right upper lobe with 1.4-cm metastatic nodule in
right middle lobe (arrow). Satellite nodule in same
lung but in different lobe from primary tumor was
previously classified as metastatic disease but is now
designated as T4.
as M1 disease in the prior edition. However,
the 5-year survival was 22% in patients patho-
logically staged with this pattern of disease,
any pattern of nodal disease (any N), and
with or without complete resection (any R).
This is identical to the 22% 5-year survival
in patients with other T4 tumors staged using
similar pathologic criteria, leading to its re-
classification as T4 [7] (Fig. 5 and Table 1).
Other masses that meet the T4 designation
include tumors that invade the mediastinum,
carina, trachea, esophagus, great vessels,
and heart (Fig. 6). Invasion of the recurrent
laryngeal nerve or vertebral body also will
lead to designation of a tumor as T4 (Fig. 7).
A B
Fig. 6—T4 designation for non–small cell lung
carcinoma.
A, Axial CT image in 51-year-old man shows 8.8 ×
6.5 cm adenocarcinoma invading into mediastinum
with invasion of right pulmonary artery, bronchus
intermedius, and carina.
B, Axial CT image in 63-year-old woman shows 7.2 ×
6.1 cm squamous cell carcinoma extending into
mediastinum, with invasion of trachea (white arrow)
and esophagus (black arrow).
C, Axial multiplanar reformation image 8 mm thick
in 84-year-old woman shows large squamous cell
carcinoma engulfing heavily calcified branches
of left coronary artery (circle). Mass also invades
and obstructs left inferior and superior pulmonary
veins (arrow). Any mass that invades mediastinum,
esophagus, trachea, carina, or great vessels is still
designated as T4.
C
Because the incidence of invasion of these new and prior TNM classifications (Table
vital structures was relatively low in the 1). These changes were validated internally
study population, survival statistics could not by the CRAB database and externally by the
be calculated, and therefore their designation SEER database. Additionally, many recent
remains unchanged. publications have also validated these rec-
Numerous changes have been made to ommendations, adding further support to the
the T designation for NSCLC between the new revisions [9–12].

566 AJR:194, March 2010


Downloaded from www.ajronline.org by 36.77.194.79 on 05/08/16 from IP address 36.77.194.79. Copyright ARRS. For personal use only; all rights reserved
A B
N Designation
The nodal (N) designation is determined
by the presence or absence of metastatic in-
volvement of lymph nodes throughout the tho-
rax (Table 1). To determine if changes needed
to be made to the N designation for NSCLC,
68,463 patients with M0 disease were evalu-
ated. However, slight differences between
the American Thoracic Society (Mountain-
Dressler) and Japanese nodal maps made sta-
tistical analysis difficult. To reconcile these
differences, a new nodal chart was created
that placed lymph nodes into seven specific
zones: supraclavicular, upper, aorticopulmo-
nary, subcarinal, lower, hilar–interlobar, and
peripheral [13] (Fig. 8). Although the nomen-
clature has changed, the general concept re-
mains the same. Patients without nodal meta-
static disease are designated as N0. Patients
with N1 disease are defined as having meta-
static involvement of lymph nodes in the ip-
silateral peripheral or hilar zones (Fig. 9).
The N2 designation signifies metastatic ex-
tension to lymph nodes in the ipsilateral me-
diastinal (upper, aorticopulmonary, lower) or
subcarinal lymph node zones (Fig. 10). The
N3 nodal designation includes metastatic in-
volvement of any nodes in the supraclavicu-
lar lymph node zone or nodes in contralater-
al mediastinal, hilar–interlobar, or peripheral
zones (Fig. 11). When survival statistics were
evaluated based on these nodal zones, sur-
vival continually decreased in both clinical-
ly and pathologically staged patients as the
nodal designation increased. For instance, in
those clinically staged with any T designation
(any T) and without extranodal metastatic dis-
ease (M0), the 5-year survival was 42%, 29%,
16%, and 7% for the N0, N1, N2, and N3 des-
ignations, respectively [3].
AJR:194, March 2010 567
New TNM Classification for Lung Cancer
Survival differences were also calculated on
the basis of the number of lymph node zones
involved in any single nodal designation. For
instance, in pathologically staged patients with
any T and M0, those with nodal metastases to
a single N1 zone had a median survival of 52
months whereas those with metastatic spread
to nodes in multiple N1 zones had a median
survival of only 31 months [3]. Similar de-
creases in survival were also seen in patients
with multiple N2 nodal zone involvement (me-
dian survival 19 months) compared with those
with disease in a single N2 nodal zone (medi-
an survival 35 months) [3]. Interestingly, these
results showed improved survival in patients
with a single N2 zone involved compared with
those with multiple N1 zones involved. These
findings, recently validated by an external
study [14], raised the possibility of subdividing
the N1 and N2 classifications into N1a (single-
zone N1), N1b (multiple-zone N1), N2a (sin-
gle-zone N2), and N2b (multiple-zone N2).
However, when these new categories were an-
alyzed in conjunction with each T stage cat-
egory, an insufficient number of patients were
present in each group for valid statistical analy-
sis. Although no changes will be made to the N
designation in the seventh edition of the TNM
classification, the above findings suggest that
overall disease burden, in addition to the an-
atomic location of pathologically involved
lymph nodes, contributes to survival.
M Designation
The M designation refers to the presence or
absence of metastatic disease within or out-
side of the thorax (Table 1). For evaluation of
the M designation, survival statistical analy-
ses were performed on 5,592 clinically staged
T4M0 and M1 patients. Clinically staged pa-
Fig. 7—T4 designation for non–small cell lung carcinoma.
A, Coronal CT image in 48-year-old woman with
increasing hoarseness and left arm weakness shows
large mass invading mediastinum with encasement
of aorta, left subclavian artery, and left recurrent
laryngeal nerve (black arrow). Mass also extends
superiorly into soft tissue of neck with edema of
subcutaneous tissues on left due to paralysis from
brachial plexus invasion (white arrow).
B, Axial CT image in 55-year-old man with adeno­
carcinoma at right apex invading vertebral body and
compressing spinal cord. Any tumor that invades
recurrent laryngeal nerve or vertebral body is designated
as T4, which is unchanged from prior system.
tients with pleural dissemination of disease,
any degree of nodal metastases (any N), and
no extranodal metastatic disease (M0) had
1-year and 5-year survival of 36% and 2%,
respectively, similar to the 45% 1-year and
3% 5-year survival in those with contralat-
eral lung nodules. This is significantly worse
survival than the 53% 1-year and 15% 5-year
survival in clinically staged patients with oth-
er T4, any N, and M0 lesions [15]. Based on
these findings, dissemination of disease to
the pleura or pericardium as well as metastat-
ic nodules to the opposite lung will now be
designated as M1a (Fig. 12). Metastatic dis-
ease outside of the thorax, with a significantly
worse 1-year and 5-year survival of 22% and
1%, respectively, has been reclassified as M1b
[15] (Fig. 13). Although there was a small but
significant survival difference between those
with single and multiple sites of extrathorac-
ic metastatic disease, not enough cases were
available for analysis to support further subdi-
vision of the M1b classification [15].
As with the T and N descriptors, exter-
nal validation has confirmed the importance
of the revisions to the M descriptor [11, 12].
When 12,901 patients with T4 or M1 disease
were evaluated from the California Cancer
Registry, the analyses confirmed that the
revised M descriptors are better correlated
with survival when compared with the prior
edition of the TNM staging system [12]. The
only discrepancy was the decreased survival
in patients with dissemination of disease to
the pericardium, a group with survival simi-
lar to those with distant metastatic disease.
Small–Cell Lung Cancer
Unlike NSCLC, SCLC is seen almost ex-
clusively in smokers and is known for its rapid
 Kligerman and Abbott

Nodal Zones Nodal Stations

Supraclavicular
Supraclavicular Low cervical
Sternal notch
Upper paratracheal (left)
Downloaded from www.ajronline.org by 36.77.194.79 on 05/08/16 from IP address 36.77.194.79. Copyright ARRS. For personal use only; all rights reserved

Upper paratracheal (right)

Prevascular
Upper
Retrotracheal
Lower paratracheal (right)
Lower paratracheal (left)
Subaortic (aorticopulmonary window)
Aorticopulmonary
Paraaortic (ascending aorta or phrenic)
Paraesophogeal (below carina)
Lower
Pulmonary ligament B C
Subcarinal Subcarinal
Hilar
Hilar–Interlobar
Interlobar
Lobar
Peripheral Segmental
Subsegmental

Fig. 8—International Association for the Study of Lung Cancer

nodal zones in revised staging system for lung cancer.
A, Comparison of seven new lymph node zones (colored rows)
compared with lymph node stations in Mountain-Dressler
classification used in prior system.
B–E, Single coronal and three axial CT images through
mediastinum show imaging-based map of location of seven new
lymph node zones (colored circles) in revised classification.
D E
doubling time, high growth fraction, early
development of metastatic disease, and ini-
tial sensitivity to chemotherapy and radiation
[16–18]. Once thought to represent nearly a
quarter of all cases of newly diagnosed lung
cancer, the incidence of SCLC has steadily
declined [19]. Despite its initial response to
treatment, the long-term survival of patients
with SCLC continues to be much worse than
that of patients with NSCLC [18].
Of the 81,015 patients with primary lung
cancers analyzed in the CRAB database,
SCLC comprised 13,290 (16.4%) cases.
Unlike NSCLC, the staging of SCLC had
previously been subdivided into two main
categories, limited disease and extensive
disease. Limited disease was classified as
disease limited to a single hemithorax, al- A B
though local extension of the primary tu- Fig. 9—N1 designation for non–small cell lung carcinoma.
mor and supraclavicular lymphadenopathy A, Curved coronal multiplanar reformation image from CT scan in 55-year-old woman with 1.7-cm right upper
lobe adenocarcinoma (T1a) and enlarged lymph node in right hilar zone (arrow).
could be present if they could be included B, Corresponding PET image shows 18F-FDG uptake in both nodule and lymph node. Metastatic disease to
in the same radiation port as the primary lymph nodes in ipsilateral hilum is designated as N1, which is unchanged.

568 AJR:194, March 2010

 New TNM Classification for Lung Cancer

mediate-grade atypical carcinoid tumors and

high-grade small cell carcinomas and large
cell carcinomas [23]. Using combined data
from both the IASLC and SEER databases,
survival analysis was performed on 1,829
pathologically staged patients with bron-
chopulmonary carcinoid tumors using the re-
Downloaded from www.ajronline.org by 36.77.194.79 on 05/08/16 from IP address 36.77.194.79. Copyright ARRS. For personal use only; all rights reserved

vised TNM staging criteria. As with NSCLC

and SCLC, as the T, N, and M designations
of bronchopulmonary carcinoid tumors inde-
pendently increased, there was a statistically
significant decrease in 5-year survival. Simi-
larly, as the stage increased, 5-year survival
Fig. 10—N2 designation for non–small cell lung Fig. 11—N3 designation for non–small cell lung decreased [8]. On the basis of these findings,
carcinoma. Curved axial multiplanar reformation carcinoma. Curved coronal multiplanar reformation
CT image in 46-year-old woman shows 3.8 × 1.8 image from CT scan in 62-year-old woman with
it has been recommended that bronchopul-
cm adenocarcinoma (T2a) in left upper lobe and 3.2 × 2.8 cm adenocarcinoma (T2a) in left upper lobe monary carcinoid tumors be staged using the
metastatic involvement to both ipsilateral hilar shows pathologic enlargement of lymph nodes in newly revised TNM classification (Fig. 15).
(white arrow) and aorticopulmonary (black arrow) subcarinal zone (arrowhead), ipsilateral upper zone
lymph node zones. Metastatic disease to ipsilateral (white arrow), and supraclavicular lymph nodes
mediastinal or subcarinal lymph nodes is still (black arrow). Metastatic involvement of any lymph Prognostic Factors
designated as N2. node in supraclavicular zone is designated as N3, Of the prognostic factors evaluated, patho-
which is unchanged from prior staging system. logic stage, sex, cell type, and age were all in-
tumor [20, 21]. All other disease was staged TNM staging system be applied to SCLC dependently significant [24] (Table 2). These
as extensive disease. (Fig. 14). This recommendation is support- factors were also significant when clinical-
Of the 13,290 cases of SCLC, 3,430 cas- ed by external validation that has also shown ly staged cases were evaluated in a separate
es of clinically staged SCLC without distant survival being more accurately predicted us- analysis [2]. Earlier stage of disease at the
metastatic disease and with full TNM data ing the revised TNM staging system [22]. time of diagnosis, female sex, and younger
were available for statistical analysis. Except age were all favorable prognostic factors [24].
for the lack of statistical significance be- Bronchopulmonary Carcinoid In terms of cell type, patients with bronchi-
tween those with N0 and N1 disease, analy- Tumors oloalveolar carcinoma, either pure or mixed,
sis showed a significant decrease in survival Bronchopulmonary carcinoid tumors are have the best survival across all calculations
as both the T and N designations increased malignant neuroendocrine tumors that are [24]. This survival benefit is well described
[21]. Similarly, except for a very small sub- divided into typical and atypical subtypes in the literature [25–30]. Survival in pa-
group of eight stage IIA patients that was a based on pathologic criteria. Carcinoid tu- tients with adenocarcinomas and squamous
statistical outlier, survival decreased as the mors exist within a spectrum of neuroen- cell carcinomas was similar when calculated
stage increased [21]. Given these findings, docrine tumors of the lung that range from across age and sex. However, when surviv-
the IASLC has recommended that the new low-grade typical carcinoid tumors to inter- al was calculated after making adjustments
for pathologic stage, cell type, sex, and age,
there was a significant survival advantage in
those diagnosed with squamous cell carci-
nomas compared with adenocarcinomas and
large cell carcinomas [24]. A similar surviv-
al advantage was also noted in patients with
squamous cell carcinomas who were clini-
cally staged with IIIA disease [2]. Although
this would suggest some survival advantage
in those with squamous cell carcinoma com-
pared with these two cell types, this benefit
is debated in the literature [31–35].
Smoking history was only available in
2,467 of the 9,173 pathologically staged pa-
tients. Current smokers had an increased in-
A B cidence of squamous cell carcinoma as well
Fig. 12—Changes to M1 designation for non–small cell lung carcinoma.
as an overall worse prognosis when com-
A, Coronal CT image in 51-year-old man with 3.4 × 3.2 cm adenocarcinoma (T2a) in right lower lobe and single pared with never smokers and prior smok-
5-mm nodule in left lower lobe (arrow), which was pathologically similar to primary tumor and was thought to ers [24]. These findings have been validat-
represent contralateral metastatic nodule. ed in multiple external studies [26, 36–38].
B, Axial CT image in 37-year-old woman with large left lung mass invading mediastinum (T4). Complex pleural
and pericardial effusions were malignant at cytology. Nodules in contralateral lung and malignant pleural or Prognosis between former smokers and nev-
pericardial disease are classified as M1a in new staging system. er smokers was less well-defined and in most

AJR:194, March 2010 569


Fig. 13—Changes to M1 designation for non–small
cell lung carcinoma.
A, Fused PET/CT image in 49-year-old man shows
2.8-cm right lower lobe nodule (T1b) with intense
18 F-FDG uptake.
B, Fused coronal image from PET/CT shows
increased FDG uptake in right adrenal gland (arrow)
and bone. Metastatic disease outside of thorax is
now classified as M1b.
Downloaded from www.ajronline.org by 36.77.194.79 on 05/08/16 from IP address 36.77.194.79. Copyright ARRS. For personal use only; all rights reserved
A B
Fig. 14—Classification of small cell lung cancer
(SCLC) using revised TNM system. Axial CT image in
59-year-old woman shows 6.2-cm SCLC extending
into mediastinum and invading pulmonary artery
without evidence of disease elsewhere (T4N0M0).
SCLC should be staged using new TNM classification
for lung cancer.
instances, there was no survival difference
between these two subsets [24].
Performance status was available in 3,027
of the 9,173 pathologically staged patients
with NSCLC. Decreased performance status
was associated with an increased mortality
and was shown to be an independently sig-
nificant factor in determining survival [24].
A similar benefit was shown in clinically
staged patients [2].
Of the 13,290 cases of SCLC, prognos-
tic factors were evaluated in 6,609 clinical-
ly staged patients. Using the prior system for
the staging of SCLC, 2,870 patients had lim-
570 AJR:194, March 2010
Kligerman and Abbott
Fig. 15—Classification of bronchopulmonary
carcinoid tumors using revised TNM system. Axial
10-mm-thick maximum-intensity-projection image
in 38-year-old woman with atypical carcinoid tumor
shows multiple nodules and masses confined to right
lower lobe without disease elsewhere (T3N0M0).
ited disease and 3,739 had extensive disease.
As seen with NSCLC, increasing age, male
sex, and decreased performance status are
all associated with decreased survival [2].
Extensive disease was also associated with
a worse survival than in those patients with
limited disease [2].
Additional factors such as biologic markers,
genetic markers, and functional imaging with
PET have shown significant prognostic impli-
cations in the literature [2, 39, 40]. However,
because the data in the CRAB database were
collected from 1990 to 2000, this information
was not available for statistical analysis.
Changes to the Staging System
In addition to revising the T, N, and M
designators, significant changes to the fi-
nal staging system were made to best cor-
relate decreasing survival with increasing
stage (Table 3). At the same time, chang-
es were made to prevent overlap in the sur-
vival curves between the different stages. In
the absence of metastatic disease, all T4 tu-
mors with N0 or N1 nodes have been down-
staged from IIIB to IIIA. T2b masses with
N0M0 disease will be upstaged from IB to
IIA and T2a masses with N1M0 disease will
be downstaged from IIB to IIA [3].
Treatment Implications
By making adjustments to the T designa-
tion, M designation, and final stage based on
both short- and long-term survival charac-
teristics, the revised staging system for lung
cancer is more accurately correlated with sur-
vival when compared with the prior staging
system. Importantly, survival statistics from
external studies have also confirmed the va-
lidity of these changes. Not only are these
changes better correlated with survival, but
they also more closely reflect trends in both
definitive and palliative treatment. For in-
stance, in the prior TNM revision, patients
with tumors designated as T4 on the basis
of invasion were at least staged as IIIB, even
those with N0M0 disease. Although these pa-
tients were classically considered nonsurgi-
cal, successful resection with improved sur-
vival has been shown to be possible in select
patients with direct invasion of the mediasti-
num, carina, pulmonary artery, vertebral
body, superior vena cava, aorta, and left atri-
um [41–47]. These findings support the shift
of locally invasive T4 tumors from stage IIIB
to IIIA in the absence of N2 or N3 and M1a or
M1b disease. Conversely, although no distinc-
tion was made between T4 tumors due to in-
vasion and T4 tumors due to malignant pleu-
ral or pericardial disease in the prior revision,
those tumors with malignant pleural or peri-
cardial dissemination were clinically subcat-
egorized as “wet IIIB.” Those patients were
deemed inappropriate candidates for defini-
tive local therapy and thus were clinically re-
garded as having stage IV disease and treated
only with systemic therapy [42, 45, 48]. Pa-
tients with satellite nodules in the same lobe
and in the same lung but a different lobe, even
in the absence of nodal metastases, would
have been staged as IIIB and IV, respective-
ly. According to the prior system, this stag-
ing would have precluded these patients from
 New TNM Classification for Lung Cancer

TABLE 2: Prognostic Factors of Survival in Pathologically Staged Patients nodal classification system will allow more
With Non–Small Cell Lung Carcinoma precise treatment. This precision will be of
Factor Median Survival (mo) Five-Year Survival Rate (%) growing importance as increased radiothera-
py doses or more aggressive combined ther-
TNM stage
apies are explored for patients with more
IA 95 66 localized disease [21]. Tumor size and in-
IB 75 56 vasion also can help determine treatment in
Downloaded from www.ajronline.org by 36.77.194.79 on 05/08/16 from IP address 36.77.194.79. Copyright ARRS. For personal use only; all rights reserved

IIA 44 43 SCLC. The term “limited disease” makes no

distinction between a small intraparenchy-
IIB 29 35
mal SCLC without nodal disease and a large
IIIA 19 23 mass invading the mediastinum with meta-
Cell type static disease to multiple ipsilateral lymph
nodes. This is an important distinction be-
Bronchoalveolar carcinoma 83 61
cause the treatments can differ. Studies have
Adenocarcinoma 45 44 shown that even when using the prior TNM
Squamous cell carcinoma 44 43 classification, patients with stage I and pos-
Large cell carcinoma 34 41 sibly those with stage II SCLC can benefit
from surgery and neoadjuvant chemother-
Adenosquamous carcinoma 26 29
apy, whereas those with more extensive lo-
Sex calized disease should receive radiation and
Female 66 52 chemotherapy alone [52–54].
Male 40 41
Limitations
Age (y) Despite the extensive power of the study,
< 70 49 46 there are some limitations to the revised stag-
≥ 70 38 38 ing system for lung cancer. The new system
is based on retrospective data that were pri-
marily collected from databases not specifi-
TABLE 3: Revisions to Stage Groupings in the Seventh Edition of the TNM
cally designed to study the TNM classifica-
Classification for Lung Tumors Compared With the Sixth Edition
tion of lung cancer [55]. Although tumor size
Stage in was often included in the data, more precise
Stage in Seventh Edition Sixth Edition N0 N1 N2 N3
information such as the exact site of tumor in-
T1a T1 IA IIA IIIA IIIB vasion and extent of lymph node involvement
T1b T1 IA IIA IIIA IIIB was often omitted. For this reason, much
T2a T2 IB IIA (IIB) IIIA IIIB of the T3 and T4 classification remains un-
changed, and no changes were made to the
T2b T2 IIA IIB IIIA IIIB
N classification despite significant survival
T3 (> 7 cm) T2 IIB (IB) IIIA (IIB) IIIA IIIB differences in those with single versus mul-
T3 (invasion) T3 IIB IIIA IIIA IIIB tiple nodal zone involvement. Additionally,
T3 (satellite nodule, same lobe) T4 IIIB (IIIA) IIIA (IIIB) IIIA (IIIB) IIIB important tumor characteristics, such as the
presence or absence of lymphangitic spread
T4 (invasion) T4 IIIA (IIIB) IIIA (IIIB) IIIB IIIB
of tumor, were not evaluated. Prognostic in-
T4 (ipsilateral nodule, different lobe) M1 IIIA (IV) IIIA (IV) IIIB (IV) IIIB (IV) formation based on tumor biology and tu-
M1a (pleural or pericardial dissemination) T4 IV (IIIB) IV (IIIB) IV (IIIB) IV (IIIB) mor genetics was not included in the study
M1a (contralateral lung nodules) M1 IV IV IV IV
because most of these data were not widely
available. Factors such as the reliability and
M1b (distant metastatic disease) M1 IV IV IV IV
accuracy of imaging in clinical staging and
Note—Cells in bold indicate a change in the stage from the sixth edition. Adjacent stage in parentheses the prognostic impact of PET imaging were
represents staging from the sixth edition.
not addressed. Staging and treatment strate-
gies were not uniform because the data were
attempted surgical resection. However, many though staging can help direct therapy, it is collected from 46 databases across 19 coun-
patients with this pattern of disease did un- important to remember that prospective clini- tries. Finally, although the new system is the
dergo surgical resection and their outcomes cal trials should be used to define optimal pa- best method to date to predict patient surviv-
were much improved compared with patients tient treatment and not staging systems based al, all of the survival data comes from ret-
with distant metastatic disease [45, 49–51]. on retrospective survival data. rospective analysis and has not been tested
This surgical evidence further supports the For SCLC, radiotherapy and chemothera- prospectively. Given these limitations, a pro-
shift in staging in the revised seventh edition py remain the mainstays of treatment [18]. spective database is currently being devel-
of the TNM classification of lung cancer. Al- However, a more well-defined tumor and oped to assess the validity of each component

AJR:194, March 2010 571


of the TNM classification as well as to assess
multiple other factors that are important in
lung cancer staging and prognosis [55].
Conclusion
Many important changes have occurred
with the adoption of the seventh edition of
Downloaded from www.ajronline.org by 36.77.194.79 on 05/08/16 from IP address 36.77.194.79. Copyright ARRS. For personal use only; all rights reserved
the TNM staging system for lung cancer.
These changes are better correlated with sur-
vival characteristics and current trends in de-
finitive and palliative therapy. Because imag-
ing plays such a crucial role in the evaluation
of lung cancer, it is imperative that radiolo-
gists become well versed in the new revision
of the TNM staging system to optimize pa-
tient care.
References
1. Jemal A, Siegel R, Ward E, et al. Cancer statistics,
2008. CA Cancer J Clin 2008; 58:71–96
2. Sculier JP, Chansky K, Crowley JJ, Van Meer-
beeck J, Goldstraw P. The impact of additional
prognostic factors on survival and their relation-
ship with the anatomical extent of disease ex-
pressed by the 6th edition of the TNM Classifica-
tion of Malignant Tumors and the proposals for
the 7th edition. J Thorac Oncol 2008; 3:457–466
3. Goldstraw P, Crowley J, Chansky K, et al. The
IASLC Lung Cancer Staging Project: proposals
for the revision of the TNM stage groupings in the
forthcoming (seventh) edition of the TNM Clas-
sification of Malignant Tumours. J Thorac Oncol
2007; 2:706–714
4. Groome PA, Bolejack V, Crowley JJ, et al. The
IASLC Lung Cancer Staging Project: validation
of the proposals for revision of the T, N, and M
descriptors and consequent stage groupings in the
forthcoming (seventh) edition of the TNM Clas-
sification of Malignant Tumours. J Thorac Oncol
2007; 2:694–705
5. Lopez-Encuentra A, Garcia-Lujan R, Rivas JJ,
Rodriguez-Rodriguez J, Torres-Lanza J, Varela-
Simo G. Comparison between clinical and patho-
logic staging in 2,994 cases of lung cancer. Ann
Thorac Surg 2005; 79:974–979; discussion, 979
6. Matin TA, Goldberg M. Surgical staging of lung
cancer. Oncology (Williston Park) 1999; 13:679–
685; discussion, 685, 689, 693
7. Rami-Porta R, Ball D, Crowley J, et al. The
IASLC Lung Cancer Staging Project: proposals
for the revision of the T descriptors in the forth-
coming (seventh) edition of the TNM classifica-
tion for lung cancer. J Thorac Oncol 2007; 2:593–
602
8. Travis WD, Brambilla E, Rami-Porta R, et al.
Visceral pleural invasion: pathologic criteria and
use of elastic stains: proposal for the 7th edition of
the TNM classification for lung cancer. J Thorac
572 AJR:194, March 2010
Kligerman and Abbott
Oncol 2008; 3:1384–1390
9. Ye C, Masterman JR, Huberman MS, et al. Subdi-
vision of the T1 size descriptor for stage I non-
small cell lung cancer has prognostic value: a
single institution experience. Chest 2009;
136:710–715
10. Rami-Porta R. New TNM classification for lung
cancer [in Spanish]. Arch Bronconeumol 2009;
45:159–161
11. Kameyama K, Takahashi M, Ohata K, et al. Eval-
uation of the new TNM staging system proposed
by the International Association for the Study of
Lung Cancer at a single institution. J Thorac Car-
diovasc Surg 2009; 137:1180–1184
12. Ou SH, Zell JA. Validation study of the proposed
IASLC staging revisions of the T4 and M non-
small cell lung cancer descriptors using data from
23,583 patients in the California Cancer Registry.
J Thorac Oncol 2008; 3:216–227
13. Rusch VW, Asamura H, Watanabe H, Giroux DJ,
Rami-Porta R, Goldstraw P. The IASLC Lung
Cancer Staging Project: a proposal for a new in-
ternational lymph node map in the forthcoming
seventh edition of the TNM classification for lung
cancer. J Thorac Oncol 2009; 4:568–577
14. Lee JG, Lee CY, Bae MK, et al. Validity of Inter-
national Association for the Study of Lung Cancer
proposals for the revision of N descriptors in lung
cancer. J Thorac Oncol 2008; 3:1421–1426
15. Postmus PE, Brambilla E, Chansky K, et al. The
IASLC Lung Cancer Staging Project: proposals
for revision of the M descriptors in the forthcom-
ing (seventh) edition of the TNM classification of
lung cancer. J Thorac Oncol 2007; 2:686–693
16. Johnson DH. Management of small cell lung can-
cer: current state of the art. Chest 1999; 116[6
suppl]:525S–530S
17. Elias AD. Small cell lung cancer: state-of-the-art
therapy in 1996. Chest 1997; 112;[4 suppl]:251S–
258S
18. Sher T, Dy GK, Adjei AA. Small cell lung cancer.
Mayo Clin Proc 2008; 83:355–367
19. Govindan R, Page N, Morgensztern D, et al.
Changing epidemiology of small-cell lung cancer
in the United States over the last 30 years: analy-
sis of the surveillance, epidemiologic, and end re-
sults database. J Clin Oncol 2006; 24:4539–4544
20. Micke P, Faldum A, Metz T, et al. Staging small
cell lung cancer: Veterans Administration Lung
Study Group versus International Association for
the Study of Lung Cancer—what limits limited
disease? Lung Cancer 2002; 37:271–276
21. Shepherd FA, Crowley J, Van Houtte P, et al. The
International Association for the Study of Lung
Cancer Lung Cancer Staging Project: proposals
regarding the clinical staging of small cell lung
cancer in the forthcoming (seventh) edition of the
tumor, node, metastasis classification for lung
cancer. J Thorac Oncol 2007; 2:1067–1077
22. Ignatius Ou SH, Zell JA. The applicability of the
proposed IASLC staging revisions to small cell
lung cancer (SCLC) with comparison to the cur-
rent UICC 6th TNM edition. J Thorac Oncol
2009; 4:300–310
23. Hage R, de la Riviere AB, Seldenrijk CA, van den
Bosch JM. Update in pulmonary carcinoid tu-
mors: a review article. Ann Surg Oncol 2003;
10:697–704
24. Chansky K, Sculier JP, Crowley JJ, Giroux D, Van
Meerbeeck J, Goldstraw P. The International As-
sociation for the Study of Lung Cancer Staging
Project: prognostic factors and pathologic TNM
stage in surgically managed non-small cell lung
cancer. J Thorac Oncol 2009; 4:792–801
25. Breathnach OS, Kwiatkowski DJ, Finkelstein
DM, et al. Bronchioloalveolar carcinoma of the
lung: recurrences and survival in patients with
stage I disease. J Thorac Cardiovasc Surg 2001;
121:42–47
26. Bryant A, Cerfolio RJ. Differences in epidemiol-
ogy, histology, and survival between cigarette
smokers and never-smokers who develop non-
small cell lung cancer. Chest 2007; 132:185–192
27. Liu YY, Chen YM, Huang MH, Perng RP. Prog-
nosis and recurrent patterns in bronchioloalveolar
carcinoma. Chest 2000; 118:940–947
28. Rena O, Papalia E, Ruffini E, et al. Stage I pure
bronchioloalveolar carcinoma: recurrences, sur-
vival and comparison with adenocarcinoma of the
lung. Eur J Cardiothorac Surg 2003; 23:409–414
29. Zell JA, Ignatius Ou SH, Ziogas A, Anton-Culver
H. Validation of the proposed International Asso-
ciation for the Study of Lung Cancer non-small
cell lung cancer staging system revisions for ad-
vanced bronchioloalveolar carcinoma using data
from the California Cancer Registry. J Thorac
Oncol 2007; 2:1078–1085
30. Campione A, Ligabue T, Luzzi L, et al. Impact of
size, histology, and gender on stage IA non-small
cell lung cancer. Asian Cardiovasc Thorac Ann
2004; 12:149–153
31. Janssen-Heijnen ML, Coebergh JW. The chang-
ing epidemiology of lung cancer in Europe. Lung
Cancer 2003; 41:245–258
32. Makitaro R, Paakko P, Huhti E, Bloigu R, Kin-
nula VL. An epidemiological study of lung can-
cer: history and histological types in a general
population in northern Finland. Eur Respir J
1999; 13:436–440
33. Devesa SS, Bray F, Vizcaino AP, Parkin DM. In-
ternational lung cancer trends by histologic type:
male:female differences diminishing and adeno-
carcinoma rates rising. Int J Cancer 2005; 117:
294–299
34. Mountain CF, Lukeman JM, Hammar SP, et al.
Lung cancer classification: the relationship of dis-
 New TNM Classification for Lung Cancer

ease extent and cell type to survival in a clinical
trials population. J Surg Oncol 1987; 35:147–156
35. Okamoto T, Maruyama R, Suemitsu R, et al.
Prognostic value of the histological subtype in
completely resected non-small cell lung cancer.
Interact Cardiovasc Thorac Surg 2006; 5:362–
366
Downloaded from www.ajronline.org by 36.77.194.79 on 05/08/16 from IP address 36.77.194.79. Copyright ARRS. For personal use only; all rights reserved
cancer patients: the Spanish Lung Cancer Group
Trial 9901. J Clin Oncol 2007; 25:4736–4742
42. Jett JR, Schild SE, Keith RL, Kesler KA. Treat-
ment of non-small cell lung cancer, stage IIIB:
ACCP evidence-based clinical practice guidelines
(2nd edition). Chest 2007; 132[3 suppl]:266S–
276S
IIIB: a retrospective analysis. (abstr) J Clin Oncol
2005; 23:9568
49. Aokage K, Ishii G, Nagai K, et al. Intrapulmonary
metastasis in resected pathologic stage IIIB non-
small cell lung cancer: possible contribution of
aerogenous metastasis to the favorable outcome.
J Thorac Cardiovasc Surg 2007; 134:386–391

36. Zhang Z, Xu F, Wang S, Li N, Wang C. Influence
of smoking on histologic type and the efficacy of
adjuvant chemotherapy in resected non-small cell
lung cancer. Lung Cancer 2008; 60:434–440
37. Tsao AS, Liu D, Lee JJ, Spitz M, Hong WK.
Smoking affects treatment outcome in patients
with advanced nonsmall cell lung cancer. Cancer
2006; 106:2428–2436
38. Toh CK, Wong EH, Lim WT, et al. The impact of
smoking status on the behavior and survival out-
come of patients with advanced non-small cell
lung cancer: a retrospective analysis. Chest 2004;
126:1750–1756
39. Erasmus JJ, Rohren E, Swisher SG. Prognosis and
reevaluation of lung cancer by positron emission
tomography imaging. Proc Am Thorac Soc 2009;
6:171–179
40. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei
AA. Non-small cell lung cancer: epidemiology,
risk factors, treatment, and survivorship. Mayo
Clin Proc 2008; 83:584–594
41. Garrido P, Gonzalez-Larriba JL, Insa A, et al.
Long-term survival associated with complete re-
section after induction chemotherapy in stage
IIIA (N2) and IIIB (T4N0-1) non small-cell lung
43. Ohta M, Hirabayasi H, Shiono H, et al. Surgical
resection for lung cancer with infiltration of the
thoracic aorta. J Thorac Cardiovasc Surg 2005;
129:804–808
44. Anraku M, Waddell TK, de Perrot M, et al. Induc-
tion chemoradiotherapy facilitates radical resec-
tion of T4 non-small cell lung cancer invading the
spine. J Thorac Cardiovasc Surg 2009; 137:441–
447
45. Gallo AE, Donington JS. The role of surgery in
the treatment of stage III non-small-cell lung can-
cer. Curr Oncol Rep 2007; 9:247–254
46. Stamatis G, Eberhardt W, Stuben G, Bildat S,
Dahler O, Hillejan L. Preoperative chemoradio-
therapy and surgery for selected non-small cell
lung cancer IIIB subgroups: long-term results.
Ann Thorac Surg 1999; 68:1144–1149
47. Fukuse T, Wada H, Hitomi S. Extended operation
for non-small cell lung cancer invading great ves-
sels and left atrium. Eur J Cardiothorac Surg
1997; 11:664–669
48. Altundag O, Stewart DJ, Stevens DC, et al. The
risk of distant metastases in patients with non-
small cell lung cancer (NSCLC) with cytologi-
cally proven malignant pleural effusion, stage
50. Roy MS, Donington JS. Management of locally
advanced non small cell lung cancer from a surgi-
cal perspective. Curr Treat Options Oncol 2007;
8:1–14
51. Battafarano RJ, Meyers BF, Guthrie TJ, Cooper
JD, Patterson GA. Surgical resection of multifocal
non-small cell lung cancer is associated with pro-
longed survival. Ann Thorac Surg 2002; 74:988–
993; discussion, 993–994
52. Waddell TK, Shepherd FA. Should aggressive
surgery ever be part of the management of small
cell lung cancer? Thorac Surg Clin 2004; 14:271–
281
53. Nakamura H, Kazuyuki S, Kawasaki N, Taguchi
M, Kato H. History of limited resection for non-
small cell lung cancer. Ann Thorac Cardiovasc
Surg 2005; 11:356–362
54. Coolen L, Van den Eeckhout A, Deneffe G,
Demedts M, Vansteenkiste J. Surgical treatment
of small cell lung cancer. Eur J Cardiothorac
Surg 1995; 9:59–64
55. Giroux DJ, Rami-Porta R, Chansky K, et al. The
IASLC Lung Cancer Staging Project: data ele-
ments for the prospective project. J Thorac Oncol
2009; 4:679–683

F O R YO U R I N F O R M AT I O N
This article is available for CME credit. See www.arrs.org for more information.

AJR:194, March 2010 573