Although the staging system applies to all forms of
bronchogenic carcinoma, from a clinical and therapeutic standpoint lung cancer is divided
into two histologic categories: small cell lung cancer and non-small cell lung cancer.
Small cell lung cancer accounts for between 15-25% of all malignant lung tumors and it is
considered to be a systemic disease best treated with chemotherapy [6]. Some patients with
limited disease at presentation will go to surgery, but post-operative chemotherapy is
used in these patients as micrometastases are suspected to be present in most patients
[6]. Because of this general consensus regarding small cell lung cancer, the discussion
below focuses on the staging, treatment, and prognosis of patients with non-small cell
lung cancer.
Complete surgical excision, combined with systematic and
meticulous mediastinal node dissection is the standard procedure for lung cancer
operations, and is defined as a radical resection or a curative operation when no residual
tumor remains after operation. Pulmonary resection without mediastinal lymph node
dissection or pulmonary resection with residual tumor remaining after the operation is a
palliative operation [6,7]. Overall surgical mortality following resection of lung cancer
is 3.7%, however, mortality is higher following pneumonectomy and in patients over the age
of 70 years [6].
There is much variability in the literature regarding
patient survival following surgical resection for bronchogenic carcinoma. The technical
considerations and approaches of surgeons vary and a mass considered unresectable by one
surgeon, may be considered technically resectable by another [8]. Factors
such as the heterogeneity of the patients studied, variations in the extent
of resection, difficulty in comparing survival data on patients from
different institutions who are treated by different surgeons, various
regimens of post-operative care (radiation or chemotherapy), and the lack of
consensus about inclusion criteria limit the conclusions that can be drawn
from many studies [8,9].
In patients that are not surgical
candidates, radiofrequency ablation can be used for treatment of lung
neoplasms [156]. The treatment is generally well tolerated and requires only
a short hospital stay [156]. Complications include pneumothorax (17%),
pleural effusion (30%), fever (46%), and some mild hemoptysis [156]. The
procedure is best performed under general anesthesia with a double lumen
endotracheal tube- this makes it possible to block ventilation to the lung
being treated which allows accurate needle placement [156].
Stage
In non-small cell lung cancer the main therapeutic
approach is surgery for stage I and II disease-- however, this subgroup constitutes only a
minority (20-25%) of patients. Patients with Stage IIIA disease may be candidates for
surgical resection, and some studies have even evaluated the benefit of surgery in certain
patients with Stage IIIB disease [2], although this group is generally considered
non-resectable. Patients with Stage IV disease are not candidates for surgical resection,
although patients with an isolated brain metastasis and otherwise resectable primary
lesion, may be an exception at certain institutions.
Unfortunately, the majority of patients with NSCLC
initially present with locally advanced or metastatic disease [2]. Estimates of the
percentage of patients whose disease is not resectable at presentation vary from 65% to
80% [4]. This helps to explain why despite advances in treatment and surgical resection
the overall 5 year survival has increased only from 8% to 13% in the last 25 years [99].
Stage I
IA: T1N0M0
IB: T2N0M0
Stage I lesions are considered surgically resectable.
Lobectomy has provided a 5-year survival of 61% for patients with clinical stage IA
disease, and 38% for those with clinical stage IB. Survival based upon surgical-pathologic
staging reveals a 5-year survival of 67-80% for stage IA, and 57-65% for stage IB lesions
[3,118,119]. Even among Stage IA patients, however, lesion size can affect
overall patient survival [157]. Five year disease free survival can be as
high as 81% for tumors less than 2 cm, but decreases to 63% for lesions over
2 cm [157]. Preoperative chemotherapy may offer a survival benefit in
patients with early stage lung cancer, but further studies will be required
[148]. There is a 15% to 20% survival benefit in patients who undergo resection of
the tumor with lobectomy, rather than a segmental resection [6], although the survival
benefit may primarily affect patients with primary lesions larger than 3.0 cm [10].
Studies also indicate that lesser pulmonary resections for T1N0 lesions are associated
with a higher risk of local recurrence [96]. None-the-less, wedge resection may be
considered as a viable alternative in patients that are not surgical candidates for more
extensive resections [107]. Another factor to consider is that
among patients who survive one lung cancer, there is a 2.5% annual risk of
developing a second primary lung cancer [157]. With earlier cancer
detection, the more lung that is preserved during the first resection the
greater opportunity for surgical resection of metachronous primary tumors
[157]. For certain frail or high risk patients, lobectomy can be
performed through the use of minimally invasive video-assisted thoracic surgery (VATS)
[117].
Stage II
IIA: T1N1M0
IIB: T2N1M0 and T3N0M0
Stage II lesions are surgically resectable, but fewer than
10% of the patients with non-small cell lung cancer are found to have metastases confined
to N1 nodes at presentation [6]. Based upon clinical staging, 5 year survival is 34%
for stage IIA, and 24% for stage IIB (T2N1M0). Clinical survival rates for patients with
T3N0M0 tumors were 22%, which supported the rationale for changing the designation of
these lesions to stage IIB from stage IIIA tumors [3]. Patients in whom stage II disease
was identified at surgery had an overall improved survival of 55-57% for stage IIA, 39-47%
for stage IIB (T2N1M0), and 34-38% for stage IIB (T3N0M0) [3,118,119]. For patients with
stage II disease, improved survival has been reported in patients with squamous cell
cancer and N1 disease when compared to patients with adenocarcinoma [6].
Preoperative chemotherapy may offer a survival benefit in patients with
early stage lung cancer, but further studies will be required [148]. Recurrence is
more likely to be local in patients with squamous cell carcinoma, while systemic
recurrence is more likely in patients with adenocarcinoma [6]. Post-operative radiation
therapy may decrease the risk of local recurrence, but does not impart a survival benefit
[6].
Stage IIB T3 lesions: T3N0M0
The surgical approach to patients with T3 tumors is
controversial. Most studies suggest patients with parietal pleura or chest wall
involvement benefit from a full-thickness chest wall surgical resection. However, the
presence of metastases to regional lymph nodes, incomplete resection, and invasion beyond
the parietal pleura are associated with a worse prognosis following resection [6,116]. The
benefit of surgical resection is less clear for patients with localized mediastinal
invasion or other T3 lesions [94,119]. Patients with T3 lesions involving the diaphragm
have been shown to have a poor prognosis and some author suggest these should actually be
considered T4 lesions [118,119,127].
For patients with chest wall invasion, 5-year post
complete resection survival rates are between 30% to 49% when regional lymph nodes are
negative [6,116,118]. The 5-year survival rate reported by the American Joint Committee on
Cancer was 38% for pathologically staged T3N0M0 lesions (now classified as stage IIB)
[3].
Superior sulcus tumors (or Pancoast tumors)
are an uncommon subset of T3 tumors which arise in the lung apex. They account for less
than 5% of all bronchogenic carcinomas [11]. In current reports, adenocarcinoma accounts
for about two thirds of cases, and squamous cell cancers make up most of the remainder
[12]. The Pancoast syndrome results from local extension into the chest wall and rib which
produces shoulder pain (the most common presenting symptom [13]); involvement of the
brachial plexus causing arm pain, weakness, and paresthesias (particularly in the ulnar
nerve distribution); and spread to the sympathetic stellate ganglion leading to Horner's
syndrome. Symptoms of Horner's syndrome are found in about 20% of patients [12] and
include ptosis of the upper eyelid, myosis, and anhydrosis; as well as constriction of the
pupil, enophthalmos (sinking in of the eyeball), narrowing of the palpebral fissure, and
flushing of the affected side of the face. Patients with Horner's syndrome have a worse
prognosis, but this is not a contraindication to surgery [12].
The following criteria usually signal a poor prognosis and
generally indicate an unresectable lesion: tumor invasion of the subclavian vessels [12]--
most commonly the subclavian artery because of it's location; phrenic or recurrent
laryngeal nerve paralysis; mediastinal lymph node involvement [12]; invasion of the
vertebral bodies [12], trachea, or esophagus; invasion of the soft tissues at the base of
the neck [13]; and distant metastases [11]. Resection of the lower cords of the brachial
plexus (if involved) may be necessary, but extensive involvement usually renders the
patient inoperable. There is some evidence that patients with ipsilateral supraclavicular
node (N3) involvement have a slightly better prognosis than patients with ipsilateral
mediastinal node involvement (N2), probably because ipsilateral supraclavicular node
involvement represents "local" tumor extension [12]. Despite this fact, overall
5 year survival is poor (approximately 14%) and pre-operative mediastinoscopy should be
used for planning appropriate treatment. It may be best to treat patients with N2 to N3
disease with irradiation alone [12].
For resectable lesions, preoperative radiation therapy is
given to reduce primary tumor size. Typically 30-45 Gy is administered 3 to 6 weeks prior
to surgery. Surgery involves en bloc resection of the chest wall, which may be accompanied
by resection of the posterior portions of the upper ribs, portions of the upper thoracic
vertebral bodies, the intercostal nerves, the lower trunks of the brachial plexus, the
stellate ganglion, a portion of the dorsal sympathetic chain, the subclavian artery, and a
lobectomy of the involved lung [13]. In addition, a careful mediastinal lymph node
dissection is carried out. In some centers any residual tumor is implanted with iodine-125
seeds [6]. The use of chemotherpy in the management of patients with superior sulcus
tumors in under investigation [13]. Surgery is associated with high morbidity (7-38%) and
mortality (5-10%) [13]. Five year survival of up to 29% has been reported in patients with
N0 disease, while prognosis is much worse for patients with nodal metastases [6,12].
Superior sulcus (Pancoast) tumors:
Example 1: This is an example of a superior sulcus tumor.
The relationship of the lesion to the left subclavian artery is nicely demonstrated (white
arrows).
NOTE: To load a higher resolution
view, simply click directly on the image below.
Example 2: This patient with a squamous cell superior
sulcus tumor demonstrates obvious rib destruction and mass invading the chest wall (black
arrows). There is loss of the tissue plane between the mass and the mediastinum and along
the anterior aspect of the vertebral body which suggests mediastinal invasion as well (T4
lesion).
Stage III
IIIA: T1N2M0, T2N2M0, T3N1M0, T3N2M0
IIIB: (Any T)N3M0, T4(Any N)M0
The five-year survival for patients with clinical stage
IIIA disease is 9% to 13%, while pathologic stage IIIA patients had a survival between 23%
to 25% [3]. Five-year survival for patients with clinical IIIB lesions was 3% to 7% [3].
Although these lesions are generally felt to be non-surgical, in certain instances
resection can be considered- particularly for higher T-stage lesions with N0 or N1 node
disease [112]. Based upon survival data, some authors also suggest that patients
with small synchronous tumor nodules in the same lobe as the primary tumor (T4 lesion)
should be considered for resection if there are no other contraindications to surgery
[113].
N2 Disease in Stage III Non-small Cell Lung Cancer
(NSCLC):
Metastases to mediastinal lymph nodes are found in nearly
half of all patients with NSCLC [6], and patients with adenocarcinoma may be at an
increased risk for the presence of unsuspected N2 node disease [15]. Unfortunately there
is a large variation in the literature on survival and prognostic factors in patients with
N2 lung cancer treated by primary surgical resection.
For patients with metastases to mediastinal lymph nodes
confirmed by preoperative mediastinoscopy, it is generally agreed that these patients do
not benefit from primary surgical intervention. The 5-year survival has been reported
to be 7% to 18% [7,15]. Patients with a pre-operative abnormal mediastinoscopy are
preferably entered into a multimodality treatment plan, including induction chemotherapy,
radiation therapy, or both, followed by potential surgery [15,16,97,125,126]. A 4-year
survival rate as high as 46% has been reported in patients following pre-operative
chemoradiation and a complete surgical resection [2].
Primary surgical resection is still worthwhile if
unsuspected N2 nodes are found at thoracotomy after a normal pre-operative mediastinoscopy
[17]. In these cases, survival has been reported to be 14% to 32% [6,7,15,18]. Improved
5-year survival in these patients following resection has been described in association
with a lower T-stage, squamous cell carcinoma cell type, fewer metastatic lymph node
levels present, and a complete resection/curative mediastinal lymph node dissection
[6,7,15,18].
Post-operative radiation may offer an added survival
benefit in certain of these patients deemed to be at increased risk for local recurrence
[16]. Post-operative chemotherapy has not been shown to result in increased patient
survival [15], although pre-operative chemotherapy (with post-operative radiation therapy)
[9] or combined pre-operative chemoradiation therapy [2] may offer a survival benefit in
select patients with N2 stage III disease. Although it is generally agreed that adjuvant
therapy can decrease local recurrence and improve disease free survival, it is not
universally accepted that these treatments have a statistically significant effect on
overall survival [97].
Non-resectable IIIA and IIIB disease:
In patients with stage IIIA or IIIB disease that is
unresectable, either surgically or because the patient is inoperable, combination
chemotherapy and radiation therapy offer the best survival benefits [97,123].
Patients with Stage IIIB lesions and malignant pleural effusions (T4 lesion) have
significant worse survival than IIIB patients without effusions (survival is similar to
patients with stage IV disease) [113]. As a result, some authors feel that it would be
more appropriate to classify the presence of a malignant pleural effusion as stage IV
disease [113].
Example: The images below illustrate a case of non-small cell lung cancer which
involved the carina (see drawing at right). Although this is typically considered a
non-resectable T4 lesion, the tumor was treated surgically with a right carinal
pneumonectomy due to the patient's young age. (Case courtsey of Dr. Douglas E. Wood,
M.D.).
Stage IV
(Any T)(Any N) M1
Five-year survival for patients with Stage IV disease is
1% [3]. Patients with stage IV lung cancer are not considered surgical candidates. Despite
the generally accepted lack of surgical options for patients with Stage IV disease, an
exception to this policy may be the patient with an otherwise resectable primary tumor and
a solitary brain metastasis presenting synchronously or metachronously. Excision of the
primary lesion and the brain metastasis with post-operative radiation therapy to the brain
can occasionally improve survival [4,6].
Synchronous Lung Tumors:
A physically distinct and separate lung tumor with a
different cell type is considered a synchronous primary lesion and should be staged
independently. Separate lesions with the same histology are more difficult to
characterize. They may be considered synchronous if there is no evidence of carcinoma in
the lymphatics common to both and no other evidence for metastatic disease exists [134].
Synchronous primary lesions account for less than 1% of lung cancer presentations [113].
Optimum therapy is surgical resection of each lesion, but patients still have an overall
worse prognosis than that expected from a single tumor of a similar stage [113,134].
