Critical Reviews in OncologylHemalology, 1991; 11: 179-207 8 1991 Elsevier Science Publishers B.V. AII rights reserved. 1040-8428/91/%3.50

ONCHEM

179

00010

Surgical treatment of lung cancer Clifton F. Mountain ofThoracicSurgery,

Department

The University of Te.ras M.D. Anderson Cancer Center, Houston, TX, U.S.A.

Contents I.

Introduction

........................................................

A. Consensusandcontroversy B. Materials II.

180

...............................................

and methods

180 180

treatment .............................. .............................................. 1. Implications of histologic type for survival ........................... 2. Surgical treatment for small cell carcinoma. ..........................

Selection A.

180

...........................................

of patients

Histologic

for surgical

classification.

180 181 181

B. Staging ............................................................. C.

Criteria

1. Resectability. a.

2.

Imaging..

for surgery

182 183

...................................................

b.

Bronchoscopy

c.

Mediastinoscopy

d.

Transthoracic

Operability

182

................................ ....................................................

for selecting patients

183

................................................

186

........................... biopsy. ..........................

and mediastinotomy needle aspiration

187 189

......................................................

189

..................... b. Cardiopulmonary evaluation and operative-risk categories .......... D. Operative morbidity and mortality ..................................... a.

III. A. B.

C. D.

E.

to thoracic

procedures

Peripheral

tumors

Other bronchoplastic

Cfifton F. Mountain received

an A.B. degree University

with the University

from School

Harvard

197&1985.

Dr. Mountain

is currently

versity of Texas M.D. Anderson of Texas Medical

Professor

Cancer

School at Houston.

of Thoracic Center

Surgery

of Surgery

191

192 193 194 194

.. .

..

195 197 198 199 200 200 200

....

. ..

201 202

College

of Medicine.

of Texas M.D. Anderson

of the new Department

190

192

chest wall.

procedures.

189

192

....... ...............

involving

cer Center since 1960, serving as Chief of the Section of Thoracic gery and Chairman

surgery

............................ ........................... Stage I and stage II disease. .................... 1. Conservative operation. .................... 2. Laser resection ............................ 3. Sleeve lobectomy.......................... Stage IIIa disease ............................. 1. Lymph node mapping. ..................... TI-3 N2 MO disease .......................... 1. Adjuvant therapy .......................... 2. Surgical procedures. ....................... T3 N&N1 disease ............................ 1. Superior sulcus tumors. .................... treatment

Surgical

and an M.D. degree from Boston has been affiliated

contraindications

Surgical

2. F.

General

He CanSurfrom

at the Uni-

and at the University

Correspondence; The University combe Boulevard,

Clifton

F. Mountain,

of Texas M.D. Houston.

Anderson

M.D.,

Professor

Cancer

TX 77030. U.S.A.

Center,

of Surgery, 1515 Hol-

180

IV. A. V.

Patterns

..........................

of failure.

Influence

of stage of disease and cell type.

Conclusion

.

.

. .

Acknowledgements Appendix....................................... References

......

. . . . . . . . . . . . . . _.....................

I. Introduction

The promise of cure offered by surgical therapy for lung cancer rests with that interval in the life history of the disease when all tumor can be completely removed. This interval is variable and enigmatic and is related to the biology of the tumor and the environment in which it develops. New understanding of the biology of the whole malignant process [l] has influenced our expectations for successful surgical treatment of lung cancer and our attempts to improve prognosis for patients with the disease. Studies of end results confirm the importance of accurate, reproducible staging and histologic classifications for optimal surgical intervention. Rational criteria for operability and resectability must also be applied.

..

......................................

202

......................................

203

._____................................

203

,........,..,,........................

204

..,,.,.....,,...................... ,,.......,............................

204 204

Anderson Cancer Center from 1965 through 1982, with follow-up through 1989, are used to illustrate the application of surgical treatment. Stage classifications conform to the recently adopted American Joint Committee/International Union Against Cancer (AJCCjUICC) International Staging System for Lung Cancer [24]. The terminal event for survival calculations is death from cancer or unknown cause; deaths within 30 days of the operation are excluded. Calculation of survival rates and tests of statistical significance between groups is according to the method of Gehan [56]. Current literature relevant to surgical treatment of lung cancer (1989-1990) indexed in the National Library of Medicine medical literature retrieval service (Medline) and recently published books and chapters were reviewed and have been integrated with the author’s experience and earlier publications.

I-A. Consensus and controversy

Agreement is general that surgery is the treatment of choice for patients with clinical stages I and II non-small cell lung cancer. Controversy exists, however, over the selection of surgical patients with stage IIIa disease, i.e., those with evidence of mediastinal adenopathy or extrapulmonary extension of the primary tumor. Interpretation of the results of imaging for staging, particularly for identifying the presence of mediastinal lymph node metastases, is also subject to argument. The question of significant benefits that may be obtained from preoperative, postoperative or pre- and postoperative adjuvant therapies remains unanswered. The potential contribution of surgery in treating small cell carcinoma continues to be questioned; results are conflicting as are opinions regarding the benefit of surgery as a part of a multimodal treatment plan or as primary therapy. I-B. Materials and methods

The end results of surgical treatment for 745 consecutive patients undergoing complete resection for nonsmall cell lung cancer at the University of Texas M.D.

II. Selection of patients for surgical treatment

The importance of standardized staging and histologic classifications in the preoperative clinical and functional evaluation of patients cannot be overemphasized. It is precisely from this information that we folmulate the treatment plan. II-A. Histologic class@kation

The present criteria for classifying the subtypes of lung cancer were published by the pathology committee of the World Health Organization in 1981 and have been widely accepted and used [7]. The four major histologic types of lung cancer - squamous cell carcinoma, adenocarcinoma, undifferentiated large cell carcinoma and undifferentiated small cell carcinoma - account for more than 97% of all malignant lung tumors. Estimates of the proportion of patients with each cell type may vary according to location. A recent report of histopathologic data from a large series [8] notes that squamous

181

cell carcinoma remains the most frequent cell type in men, followed by adenocarcinoma, while in women, adenocarcinoma is most frequent, followed by small cell carcinoma. The report also points out that the incidence of small cell carcinoma is apparently increasing and may become the most commonly diagnosed tumor in women. II-A.1.

Implications of histologic type for survival

When morphology is considered as an independent variable, the best overall survival following resection, in my own experience, has been achieved for patients with squamous cell carcinoma [9]. Survival rates for those with adenocarcinoma and undifferentiated large cell carcinoma have been remarkably similar, and poorer than the end results for patients with squamous cell tumors. Early studies of patients undergoing resection for lung cancer (prior to contemporary refinements in imaging techniques) included 41 with small cell carcinoma for whom surgery was the single-modality primary treatment [lo]. The outcome was disastrous, reflecting the ineffectiveness of surgical treatment to influence survival in this group of patients (Fig. 1).

Undifferentiated

\ 20.

iarge

\

Cell INs83)

\ \

Oj 0

\

Undifferentiated Small Cell (N=41) -‘*_

\ ,,

Fig. 1. Cumulative expected (Surgical

proportion collected

IN MONTHS

of patients

to survive 5 years following patients,

60

40

20 SURVIVAL

series,

with primary

resection, American

according Joint

lung cancer to cell type

Committee

for

Cancer Staging and End Results Reporting, Task Force on Lung). From: Mountain CF. Assessment of the role of surgery for control of lung cancer.

Ann Thorac

Surg 24: 365, 1977 (with permission).

II-A.2.

Surgical treatment for small cell carcinoma

Over the years many patients with small cell tumors have been treated surgically, often for undiagnosed pulmonary nodules. Retrospective reviews consistently relate the best prognosis for small cell carcinoma to small groups of patients, selected from larger series, whose treatment plan included surgery [11,12]. The advent of more effective chemotherapy, and studies documenting a pattern of failure at the primary site in patients achieving a complete response, has prompted a re-evaluation of the role of surgery for small cell tumors. Although the contribution of surgery to overall management remains controversial, there is little argument that rapid growth and dissemination is the hallmark of small cell carcinoma. Accordingly, we would not expect a local treatment modality such as surgery to have substantial impact on mortality for patients with this type of tumor. Reports of surgical treatment must be quantitatively related to when and how small cell carcinoma, as a clinical entity, is likely to benefit from resection [13]. Because only 10% of patients are potentially candidates for definitive operation, it is important to keep the population denominator in mind when results are evaluated. A recent retrospective review of 97 patients with small cell carcinoma who underwent surgery from 1977 through 1986 noted that 28% of the group had clinical stage I disease; 30%, stage II; and 42%, stage III. These patients represented about 5% of the estimated small cell population. Five-year cumulative survival rates of 35%, 23% and OS, respectively, were reported following surgery alone for patients with stages I and II tumors, and surgery plus chemotherapy (cyclophosphamide, doxorubicin, vincristine) for those with stage III. The results suggest a sizable error in assessing early-stage disease, but show a surprisingly good outcome for the patients with stages I and II tumors of this cell type [14]. The International Society of Chemotherapy Lung Cancer Study Group (ISC-LCSG) has entered 156 patients with stages I or II small cell carcinoma into a study of initial surgery with adjuvant chemotherapy. The results (as of August 1989) were as follows: a cumulative survival rate at 5 years of 48% for 19 patients with stage I disease; 25% for 24 patients with stage II; and 24% for 20 patients with stage III [15]. The theoretical biologic advantages of a clean surgical resection that immediately induces clinically complete remission have been described [16], and a survival advantage has been reported for patients in the Tl-3 NO MO subsets who receive postoperative chemotherapy [ 17,181. A number of studies also document an improved prognosis for patients with stages I and II small cell carcinoma when treatment is with surgery and postoperative chemotherapy [ 19-221. Results are generally poor, however, for pa-

182

tients with N2 disease. For this reason, mediastinoscopy is recommended to confirm pretreatment staging. Definitive end results for patients with stages I and II small cell carcinoma treated with nonsurgical therapies are not known, and clinical trials comparing the effectiveness of surgery and postoperative chemotherapy with nonsurgical treatment (which would require at least 150 patients derived from a small cell population of 1500 patients [23]) have not been conducted. The responsiveness of small cell carcinoma to chemotherapy is known, however, and the results of recent investigations consistently point to improved survival rates for patients with stages I and II disease who undergo surgery and postoperative chemotherapy. Surgery and postoperative chemotherapy therefore appears to be a valid treatment option for those patients [24]. The potential of surgery to provide a complete remission and prolong survival for patients with stage III disease who undergo induction chemotherapy has been addressed in a number of studies [ 15,25-271. Preceeding resection with chemotherapy has practical advantages; not only can the tumor response be evaluated pathologically, but also the resected specimen allows more precise histopathologic study that may have important therapeutic implications. For example, non-small cell tumor components that are not responsive to further chemotherapy may be identified. Our pilot study at the M.D. Anderson Cancer Center [28] revealed a high incidence of non-small cell tumors in the postchemotherapy resected specimens: 23% (6/26) were adenocarcinoma; 4% (l/26), adenosquamous carcinoma; 4% (l/26), squamous cell carcinoma and 8% (2/26) were atypical carcinoids. Similar findings have been reported by Baker et al. [26]. Researchers have also noted that only a fraction of the patients included in feasibility studies of adjuvant surgery are deemed resectable. The United States National Cancer Institute Lung Cancer Study Group (LCSG) has completed a prospective, randomized clinical trial comparing conventional therapy for small cell carcinoma to a regimen of induction therapy, surgery, and postoperative therapy, but the results have not been published. Although retrospective studies have reported both positive and negative results, there is no substantial, reproducible evidence that adding surgery to conventional regimens for stage IIIa disease improves the results of chemotherapy or combined chemotherapy and radiotherapy protocols. These regimens continue to be the treatments of choice for patients with stages IIIa and IIIb small cell carcinoma. The addition of surgical treatment remains in the realm of investigational therapy until the results of clinical trials resolve the question [29].

II-B.

Staging

The International Staging System For Lung Cancer [4] is important for us today both clinically and in research. It is useful because of the relationship between disease extent, treatment selection, and prognosis. This staging system, based on TNM (T-primary tumor, N-regional lymph nodes, M-distant metastasis) principles, has been accepted internationally, providing a means for effective communication of information about cancer patients in all parts of the world. It represents a revision and unification of earlier staging recommendations of the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC). The nomenclature includes classification for 17 discrete levels of lung cancer in terms of the extent of the primary tumor, the limits of regional lymph node spread, and the presence or absence of distant metastasis. The TNM anatomic subsets afford more specific and reproducible classifications than the broad designations of ‘limited’ and ‘extensive’ disease - terms that often have been used, and often inconsistently, to designate patients with and without supraclavicular lymph node metastasis or distant metastasis. TNM subsets with similar survival expectations are combined into five stages of disease that can be related to prognosis and to the philosophies of contemporary treatment planning (Tables 1 and 2). It is essential that the same TNM and staging definitions be applicable for clinical and pathologic staging and for staging at any other time during life history of the disease. This consistency is especially important to perioperative regimens and multistep treatment plans that assign patients to additional phases of treatment based on a post-treatment evaluation of disease extent. ‘Clinical staging’ (cTNM) includes all information obtained before beginning treatment and is not changed in light of subsequent information. ‘Pathological staging’ (pTNM) is based on the additional information obtained from pathologic examination of resected specimens. ‘Retreatment staging’ (rTNM) may be applied after induction therapy or at any time that evaluation of disease extent is important to clinical management or reporting of end results [30]. II-C.

Criteria for selecting patients for surgery

The decision to operate on patients with lung cancer is based on criteria for resectability and criteria for operability. Criteria for resectability involve the technical considerations for removal of all the cancer - cell type and stage of disease are major indicators of the potential for accomplishing a complete resection. Criteria for

183

TABLE

1

TNM descriptors Primary

Tumor

TX

[4] (T)

Tumor

proven

scopically.

by the presence

or any tumor

TO

No evidence

TIS

Carcinoma

Tl

A tumor

of primary

cells in bronchopulmonary

be assessed as in a retreatment

but not visualized

roentgenographically

or broncho-

tumor.

that is 3.0 cm or less in greatest

dimension,

surrounded

by lung or visceral pleura,

and without

evidence

of invasion

proximal

at bronchoscopy.”

A tumor more than 3.0 cm in greatest

dimension,

or obstructive

to the hillar region.

a lobar

secretions staging.

in situ.

to a lobar bronchus T2

of malignant

that cannot

pneumonitis

bronchus

extending

or a tumor of any size that either invades the visceral pleura or has associated At bronchoscopy.

or at least 2.0 cm distal to the carina.

Any associated

the proximal atelectasis

extent of demonstrable

or obstructive

tumor

pneumonitis

atelectasis

must be within

must involve less than

an entire lung. T3

A tumor

of any size with direct extension

or pericardium

without

2 cm of the carina T4

A tumor

without

Involvement

of malignant

into the chest wall (including

the heart, great vessels, trachea,

involving

of any size with invasion

or presence Nodal

involving

the carina,

of the mediastinum

atelectasis

or involving

s&us

or obstructive

heart,

tumors),

or vertebral

diaphragm,

body, or a tumor

pneumonitis

great vessels. trachea,

or the mediastinal

pleura

in the main bronchus

within

of entire lung. esophagus,

vertebral

body or carina

pleural effusion.b

(N)

NO

No demonstrable

Nl

Metastasis

to lymph nodes in the peribronchial

N2

Metastasis

to ipsilateral

Metastasis

to contralateral

N3

or associated

superior

esophagus

metastasis

to regional

mediastinal

lymph nodes. or the ipsilateral

hilar region, or both, including

lymph nodes and subcarinal

mediastinal

direct extension.

lymph nodes.

lymph nodes, contralateral

hilar lymph nodes, ipsilateral

or contralateral

scalene or supraclavicu-

lar lymph nodes. Distant

Metastasis

(M)

MO

No (known)

Ml

Distant

‘Tl: The uncommon main bronchus

distant

metastasis

elements

superficial

tumor

Specify site(s). of any size with its invasive

component

associated

with lung cancer are due to tumor.

dictate

is negative

that the effusion

for tumor,

to the bronchial

wall which may extend

proximal

to the

is not related

There are, however,

some few patients

the fluid is non-bloody

to the tumor,

the patients

in whom cytopathological

and is not an exudate. should

examina-

In such cases where these

be staged Tl, T2 or T3, excluding

effusion

element.

operability involve determination of the patient’s ability to survive the operation (i.e., adequate cardiopulmonary status) and to tolerate the required loss of lung tissue. II-C.1.

limited

I.

fluid (on more than one specimen)

and clinical judgment

as a staging

present.

is classified as T

bT4: Most pleural effusions tion of pleural

metastasis

Resectability

Little or no argument exists concerning the selection of patients with clinical stages I and II non-small cell lung cancer for definitive surgical treatment. Our own

end results [31] and those of others [32,33] also support operation as a valid option for selected patients with stage TIIa tumors; however, some controversy regarding this point remains, particularly when patients have evidence of mediastinal adenopathy. II-C.1 .a. Imaging

Imaging studies contribute

to the assessment of the

184

TABLE

2

Stage grouping Stage

of TNM’ subsets [24] TNM subset

Occult TX

NO

Stage 0

TIS

carcinoma

Stage I

Tl

NO

MO

T2

NO

MO

Stage II

Tl

Nl

MO

T2

Nl

MO

carcinoma

Stage IIIa

Stage IIIb

Stage IV

MO in situ

T3

N2

MO

Tl

N2

MO

T2

N2

MO

T3

NO

MO

T3

Nl

MO

T4

NO

MO

T4

Nl

MO

T4

N2

MO

Tl

N3

MO

T2

N3

MO

T3

N3

MO

T4

N3

MO

any T

any N

Ml

“TNM, tumor-node-metastasis.

primary tumor and to the evaluation of the regional lymph nodes. Several techniques are often used to search routinely for distant metastatic disease in asymptomatic patients; however, there is no scientifically reproducible evidence that any modality detects clinically silent brain or bone metastasis in a meaningful number of them [34]. Ichinose et al. [35] retrospectively examined the survival data, the relationship between recurrence sites and preoperative examinations, and the discovery rate for occult metastases in 222 patients with stages I and II non-small cell carcinoma who underwent curative operation. They concluded that the routine use of radionuclide scans or computerized tomography (CT) scans was of no benefit to asymptomatic patients with early, localized disease. Salvateirra et al. conducted a prospective study of 146 patients with potentially resectable non-small cell lung cancer who underwent preoperative CT scans of the brain, chest, and upper abdomen, abdominal ultrasonography, and whole body radionuclide bone scans [36]. Brain CT detected silent brain metastasis in 2.7%; whole-body radionuclide bone scanning identified silent bone metastasis in 3.4%; and CT of the upper abdomen and ultrasonography detected silent hepatic metastasis in 9.3%. After integrating these results with the incidence of metastases by TN stage and histologic type, and the significance of clinical signs and symptoms for predicting metastatic disease, the authors recommended the following protocol for extrathoracic staging of surgical patients: abdominal ultrasonography or upper-abdominal CT or both of all

patients except those with asymptomatic stage I squamous cell carcinoma; brain CT of all patients with adenocarcinoma and large cell carcinoma and of those with squamous cell carcinoma who have suspect neurological signs; and a radionuclide bone scan only if clinical and laboratory indicators are present. Our current practice at the M.D. Anderson Cancer Center for patients with disease other than clinical Tl NO MO is to obtain CT of the chest and upper abdomen from the thoracic inlet down to and including the adrenal glands. If a patient is referred after a recent CT examination that excludes upper abdominal scanning, we perform ultrasound studies of the liver or limited CT of the upper abdomen in an effort to detect hepatic and adrenal masses before operating. There are few data, however, that confirm detection of one or more malignant deposits in a substantial number of patients. In the research environment of a categorical institution, CT of the brain and radionuclide scans of the skeletal system of resectable patients are performed more routinely to meet investigational-treatment protocol requirements than might be recommended in other settings; however, this does not infer that we are able to detect silent metastases with any greater frequency than is reported by others. Pleural e$iision. About 12% of patients with lung cancer present with clinical evidence of pleural effusion. The fluid is usually tumor-related, portends a poor prognosis, and indicates an unresectable tumor. This is

185

true whether or not malignant cells are identified. In our studies, the outcome for patients with malignant cells identified in the fluid was essentially the same as the survival for those with no examination of the fluid or with negative cytology (Fig. 2). For this reason, in the absence of cytological studies, we assume that pleural effussion that is clinically determined to be tumor-related is stage IIIb (T4) disease, and that its presence portends unresectability. If the source of the effusion is considered to be clinically unrelated to the underlying malignancy, then thoracentesis and cytological examination of the fluid must be performed. In a few patients the effusion may be related to associated infection or an inflammatory condition. If this can be established, the effusion can be treated accordingly and does not influence the staging or the decision for operation. Solitary pulmonary nodules.

In evaluating solitary pulmonary nodules, Swensen et al., have emphasized the importance of (i) comparing the patient’s current chest roentgenogram (CXR) with the patient’s previous films and (ii) using thin section CT to visualize lesions whose malignancy remained indeterminate after fluoroscopic and linear tomographic studies were completed [37]. CT of the lungs has greater sensitivity for detecting additional pulmonary nodules than do conventional CXRs and tomograms. Some clinicians consider CT unnecessary for patients with small peripheral tumors and an otherwise negative chest radiograph (clinical stage Tl NO MO) [38], whereas others [39] consider that it should

I

I

0

12

24

36

48

60

Months Following Treatment

Fig. 2. Patients proportions absence Mountain System

with clinical

expected

of malignant

of pleural

5 years according

cells or no examination

CF. Prognostic for Lung

evidence

to survive

Cancer.

implications Semin Oncol sion).

effusion;

cumulative

to the presence of the fluid.

of the International

or

From: Staging

15: 236, 1988 (with permis-

be a routine examination for all patients with MO disease. Webb notes that CT evaluation of the hilum provides a detailed view of the bronchi and hilar vessels and may allow identification of endobronchial lesions, which could help the bronchoscopist to select biopsy locations. CT delineates hilar and parahilar masses and, in some instances, can identify contiguous spread that involves the mediastinum [40]. When contiguous shadows are present, however, invasion of the mediastinal structures can be identified with certainty only if other features are present, i.e., a compressed blood vessel, tumor shadow extending beyond the midline of the body or around the contralateral vessel, or displacement of the lower trachea and bronchus by tumor pushing against it. For indeterminate lesions, resectability of the tumor can be determined only by exploratory thoracotomy. The newer generation of magnetic resonance imaging equipment may help to resolve these problems, as it does in confirming vascular and neurologic involvement. Mediastinal lymph nodes. In performing the clinical evaluation of surgical candidates, the area of greatest controversy lies in interpreting CT imaging of the mediastinal lymph nodes. Libshitz notes that “Virtually any figure desired can be found in the literature regarding the sensitivity and specificity of CT in the evaluation of mediastinal lymph nodes in bronchogenic carcinoma” [38]. The ‘normal’ size for these nodes has not been agreed on, and reports regarding the implications of nodes imaged as abnormal are conflicting; however, the radiologist’s determination of a negative mediastinum on CT is about 90% accurate and, in this instance, further invasive determinations of resectability are usually unnecessary. Patterson et al. recommend mediastinoscopy as a routine staging procedure to accurately select those patients who are suitable candidates for thoracotomy and in whom a complete resection can be expected [41]. These authors conducted a prospective evaluation of magnetic resonance imaging (MRI), CT and mediastinoscopy for preoperative assessment of mediastinal lymph node status in 170 patients with suspected primary lung cancer. The accuracy, positive predictive and negative predictive values, respectively, of CT were 82%, 79% and 84%. The findings from MRI were essentially the same but the results from CXR were substantially lower. The accuracy of mediastinoscopy, however, was 95%, and the positive and negative predictive values were both 100%. The authors conclude that mediastinoscopy is the most accurate staging investigation in the routine management of patients with lung cancer. In contrast to these recommendations, Thermann et

186

Magnetic resonance imaging. The contribution of magnetic resonance imaging (MRI) to the evaluation of thoracic surgical candidates remains to be fully developed [44]. The strengths of the examination include excellent depiction of the heart and great vessels, chest wall, spinal contents, vertebral bone marrow and brachial plexus [45]. It is useful as an adjunct to CT for resolving problems that require clarification of specific anatomic features. MRI is the modality best able to assess direct invasion of the mediastinum and neural foramina by tumors lying posteriorly and against the mediastinum (Fig. 4A and B) [31]. It is also superior to CT in identifying vascular involvement or invasion of the pericardium or heart. If CT findings are inconclusive, MRI can be of value for defining possible hilar or mediastinal masses.

al. [42] conducted a study of CT as a selection method for mediastinoscopy in 75 patients. In 22/75 (29.3%) patients CT examination was positive for mediastinal adenopathy. The negative predictive value of the scans was 94% (50/53). Three of 63 patients with lung cancer (4.8%) had false negative CT scans and 2/63 (3.0%) were false positive. The authors note that routine mediastinoscopy adds substantial cost to patient management and conclude that a policy of selective mediastinoscopy is a valid way of avoiding unnecessary mediastinoscopies and unhelpful thoracotomies. I recommend mediastinoscopy, mediastinotomy or both to determine the histologic status and resectability of the nodal disease in patients who might be denied surgery on the basis of the radiologist’s determination of enlarged nodes [43]. This recommendation is based on our studies documenting a low positive predictive value of CT for patients who are otherwise operable (Table 3). Several factors will influence reports of accuracy, sensitivity, specificity, and positive and negative predictive values of CT imaging of the mediastinal lymph nodes. The completeness of nodal dissection at thoracotomy is the major element; the population examined will also influence the results of imaging, e.g., patients from an area of known granulomatous disease will have a higher incidence of enlarged nodes.

II-C.1.b. Bronchoscopy Preoperative bronchoscopy is mandatory for all patients prior to thoracotomy. It provides essential information regarding the tumor’s proximal margins and thus the extent of resection that will be required. If a diagnosis has not been made, one can frequently be determined by cytological examination of specimens obtained by bronchial washing and aspiration; this is especially useful when the cancer lies beyond the range of biopsy or the range of vision. Bronchoscopic brushings or curettement under fluoroscopic control provide reliable and safe approaches to the diagnosis of peripheral tumors. Transbronchial needle biopsy helps to define the status of lymph nodes. Findings at bronchoscopy that suggest unresectability are evidence of recurrent nerve involvement with paralysis of the vocal cord, invasion of the trachea, broadening and fixation of the carina, or presence of a tumor within 2 cm of the carina. These criteria are relative; e.g., some patients with tumors involving the trachea, carina or

Imaging of tumors invading the chest wall. Chest CT examination may be useful in evaluating peripheral tumors that invade the chest wall if the invasion is definite or if bony destruction is present, but equivocal masses cannot be delineated accurately. Clinical evidence of invasion of the vertebral body by tumors originating in the superior sulcus of the lung usually contraindicates resection; however, if the tumor abuts the vertebra and the bony cortex appears intact, complete resection can be anticipated (Fig. 3A and B) [3 11.

TABLE

3

Mediastinal

nodal assessment

(n = 102 patients) CXR”

CTc,A

TOMOb

Sensitivity

3125

(12%)

5125

(20%)

15125

Specificity

71/77

(93 k)

69117

(89%)

46111

(60 k)

Accuracy

741102

(74%)

74/102

(74%)

61/102

(61%)

319 71193

(33%) (76%)

5113

(39%) (78 %)

15147 46155

(32%) (84%)

Predictive

value of (+) test

Predictive

value of (-)

test

69/88

(60 %)

=CXR, chest X-ray. bTOMO,

chest standard

‘CT, chest computed

tomography.

tomography.

QZT criterion for a positive node is 1 cm. From: McKenna RJ, et al. Roentgenologic permission).

evaluation

of mediastinal

nodes for preoperative

assessment

in lung cancer.

Chest 88: 206, 1985 (with

187

Fig. 3. (A) Computerized tomographic (CT) scan of the thorax illustrating a T3, operable, superior sulcus tumor. (B) CT scan of the thorax illustrating a T4. inoperable, superior sukus tumor. From: Mountain CF. Expanded possibilities for surgical treatment of lung cancer. Survival in stage IIIa disease. Chest 97: 1045.1990 (with permission)

proximal main bronchus choplastic procedures.

may be candidates

for bron-

II-C.1.c. Mediastinoscopy and mediastinotomy Mediastinoscopy [46] and mediastinotomy [47] are useful in all patients for whom questions of diagnosis and resectability remain unanswered. In our practice, these procedures are usually not performed when patients have peripheral tumors and a normal-appearing hilum and mediastinum; however, opinions differ regarding indications for mediastinoscopy and mediastinotomy. A poorer prognosis has been documented for patients with ipsilateral mediastinal metastases con-

firmed at mediastinoscopy than for those whose mediastinoscopy is negative and whose mediastinal lymph node metastasis is found only at thoracotomy [48]. A recent review of 470 mediastinoscopies found that mediastinal biopsies were positive for 48/161 (30%) patients with peripheral tumors [49]. These results, along with evidence that normal-appearing nodes often contain metastatic disease [43], have prompted some surgeons to include mediastinoscopy as a routine procedure in patients under evaluation for lung cancer surgery. Transcervical mediastinoscopy permits direct surgical exploration and biopsy of the middle and posterior portions of the superior mediastinum. I reserve this proce-

Fig. 5. Chest roentgenogram showing mediastinoscope in place and relationship of the instrument to thoracic structures (line drawing indicates trachea, carina, and main stem bronchus).

Fig. 4. (A) Chest roentgenogram (CXR) of a superior sulcus tumor in the apex of the right lung. (B) Magnetic resonance imaging (MRI) showing invasion of the neural foramina that could not be seen on CXR or computerized tomography (CT) scan (V = vertebra, T = tumor). From: Mountain CF. Expanded possibilities for surgical treatment of lung cancer. Survival in stage IIIa disease. Chest 97: 1045, 1990 (with permission).

dure, however, for patients who have been examined by conventional methods and for whom the results of bronchoscopy and sputum cytology are available. It is important to appreciate anatomic features as they relate to the extent of the examination. As shown in Fig. 5, the mediastinoscope lies directly anterior to the trachea and beneath the pretracheal fascia. The lymph nodes of the anterior mediastinum are not accessible because the instrument is posterior to the innomi-

nate artery and vein and to the arch of the aorta. Standard mediastinoscopy permits biopsy and examination of both peritracheal regions, the subcarinal space, and about 2 to 3 cm along each mainstem bronchus. Criteria for unresectability according to the findings at mediastinoscopy are: (i) a diagnosis of small cell carcinoma, (ii) involvement of the contralateral paratracheal lymph nodes, (iii) involvement of ipsilateral paratracheal lymph nodes in the upper half of the intrathoracic trachea, (iv) direct invasion of the trachea, and (v) evidence of gross perinodal disease. Mediastinotomy, which allows evaluation of the subaortic area and the anterior hilar area at the pulmonary artery root, is of particular value in evaluating lesions arising within the left upper lobe. Because of the relationship of these tumors to the aortic arch, they are frequently underevaluated at mediastinoscopy. Ginsberg et al. note that bronchogenic carcinoma of the left upper lobe frequently metastasizes to lymph nodes not only in the anterior mediastinum, but also in the superior mediastinum. These authors developed a technique to explore and sample nodes from both regions by extending a standard cervical mediastinoscopy. Analysis of the first 100 procedures confirmed that the technique, in their hands, was accurate, safe and effective as a single staging procedure for preoperative assessment of primary tumors of the left upper lobe [50].

189

The value of combined cervical and parasternal mediastinoscopy (for evaluation of the periaortic lymph nodes) has been described by Laquet et al. for patients with clinically operable lung cancer in both central and peripheral locations in the left upper lobe [51]. Using the combined procedure, the authors report an increase in resectability and a decrease in the number of incomplete and palliative resections. II-C.1.d. Transthoracic needle aspiration biopsy

In general, I believe that fine-needle aspiration biopsy is not indicated for good-risk surgical patients who have peripheral solitary nodules 2 cm or less in diameter, if both definitive diagnosis and treatment can be accomplished by open thoracotomy. The implications of indeterminate biopsy results and the possible complication of pneumothorax influence this policy. To minimize operations for benign tumors but avoid the risk of a delayed diagnosis of malignancy, the nonradiologic information ~ i.e., age, history of previous malignancy, smoking history and review of previous films - should be carefully evaluated. This latter element can be so important that significant efforts to obtain previous films are justified, because this information will influence subsequent interventions. However, ‘watchful waiting’ is seldom, if ever, an option for middle-aged and older patients unless benignancy is proved. As mentioned earlier, Swensen et al. recommend an integrated approach to the evaluation of solitary pulmonary nodules that includes thin-section CT (1 .(r5.0 mm-thick sections) and phantom densitometry for indeterminate lesions (2 cm or less in diameter) to show calcification or fat; however, they note that about a third of these tumors remain radiologically indeterminate [37]. Aspiration needle biopsy may be required to obtain a diagnosis of synchronous multiple primary tumors or metastasis if multiple or bilateral nodules are imaged or if patients are to receive preoperative therapies (Fig. 6).

Fig. 6. (A) CXR showing

II-C.2.a.

General contraindications to thoracic surgery

Most patients with lung cancer have concomitant disease of the cardiorespiratory system such as bronchitis, emphysema and cardiac-related disease. A major compromise of pulmonary function or serious cardiovascular, hepatic, or renal disease contraindicates pulmonary resection. For a patient who has recently experienced a myocardial infarction, the decision concerning pulmo-

by associated

biopsy = adenocarcinoma) pneumonia.

to l-cm nodule in the left upper lobe of uncertain loma, second primary,

II-C.2. Operability Operability is a determination of the patient’s ability to survive the stresses of anesthesia and thoracic operation, and to tolerate the sacrifice of lung tissue required for complete resection of the disease.

mass (bronchial

in right hilum partly obscured

phy showing

metastatic

a fine-needle cytologic

i.e., granu-

disease. (B) Computerized

tomogra-

aspiration

diagnosis

Arrow points

etiology,

biopsy of left upper lobe nodule;

= large cell carcinoma.

nary surgery depends on the functional status of the heart and the anatomic status of the coronary arteries. Evaluation of these patients should include cardiac catheterization, and the timing of surgery should be decided on an individual basis. Pulmonary hypertension is a specific contraindication to lung surgery, and a high risk of mortality accompanies uncontrolled arrythmia. Electrocardiographic abnormalities are common in patients with lung cancer evaluated for surgery; however, operation is not precluded by a bundle branch block. A

190

right bundle-branch block or left anterior fascicular block carries the least risk; left posterior fascicular blocks are intermediate; combination or bifascicular blocks entail the highest risk. If myocardial ischemia is present in a patient with a biologically favorable tumor that is technically resectable, coronary arteriography should be performed. If the coronary arterial disease is surgically correctable, simultaneous resection of the tumor and coronary artery bypass is a reasonable consideration. A recent report of pulmonary resection combined with cardiac operations in 21 patients, eight with malignant disease (Tl NO MO non-small cell lung cancer), supports the policy that combining pulmonary resection with a cardiac operation is safe and offers a favorable prognosis for selected patients [.52]. If complete resection of the lung tumor is anticipated, the combined procedures may also be applied in good-risk patients with stages II and IIIa disease, as well as in those with stage I.

TABLE

4

Cardiopulmonary

Group

Indeterminate surgical-risk category. For these patients of indeterminate surgical risk, regional pulmonary function studies using [133] xenon gas as a radioactive marker have proved helpful in predicting the degree of resection that may be tolerated. Knowing the contribu-

surgical-risk

groups

I- low surgical

risk

Cardiac Normal

size and cardiac

Normal

blood pressure

Normal

electrocardiogram

function

Pulmonary Normal

arterial

Satisfactory

blood gases

overall mechanical

lung function

FEV, > 70% of

predicted Group

II

very high surgical

risk

Cardiac Intractable

congestive

heart failure

Intractable

ventricular

arrhythmia

Recent myocardial

infarction

Pulmonary Poor overall mechanical

lung function

(irreversible):

FEV,

< 35%

of predicted Irreversible

CO2 retention:

Pulmonary

hypertension

II-C.2.b. Cardiopulmonary evaluation and operative-risk categories

A basic evaluation including information from the history, physical examination, specific laboratory studies, and spirometric assessment of mechanical ventilatory function permits assignment of patients to the three functional groups shown in Table 4 [53]. The forced expiratory volume during the first second, FEVi, which is expressed as a percentage of the patient’s predicted value, is the most valuable measurement in routine spirometric assessment. The first surgical-candidate group includes patients at low surgical risk who have no specific, absolute, or relative contraindications to a lung resection up to and including pneumonectomy. Patients in the second group are at very high risk, and surgical treatment is not in their best interest. This group includes patients with intractable congestive heart failure, pulmonary hypertension, and irreversibly compromised overall lung function. Most patients with lung cancer fall in a third group, that is, they demonstrate a mild to moderate degree of cardiopulmonary abnormality. These patients have relative cardiopulmonary contraindications to pulmonary resection, and both the decision for operation and the extent of safe resection require further evaluation.

evaluation:

Group

PCOr

> 45 mm Hg

III - mild to moderate

surgical

risk

Cardiac Coronary

artery disease

Angina

pectoris

Myocardial

infarction

Electrocardiographic Cardiac

within 3 years abnormalities

arrhythmias

Systemic hypertension Myocardial Valvular

dysfunction

(low ejection fraction)

heart disease

Pulmonary Hypoxia

with normal

Reduced

overall pulmonary

Adapted

PCOr function

FEV, 35-70s

from: Ali MK et al. Physiological

with lung cancer,

In: Mountain

rent Status and Prospects Press, 1986; 99-104

evaluation

of predicted of the patient

CF, Carr DT, eds. Lung Cancer,

for the Future.

Austin:

University

Cur-

of Texas

(with permission).

tion of each lung, and of each zone within each lung, to overall pulmonary function can lead to an accurate prediction of the patient’s anticipated postoperative functional status. Measures of regional function help establish the integrity of both the tumor-bearing and the contralateral lung. This technique offers one of the most accurate methods of predicting the functional loss that accompanies total or partial lung resection. The methodology for split and regional lung function evaluation with xenon scanning has been described in detail elsewhere [54]. Patients in the intermediate-risk group will tolerate pneumonectomy if the calculated postpneumonectomy

191

FEV, is more than 35% of predicted and the regional distribution of function within the non-tumor-bearing lung follows the normal pattern of rising ventilation and perfusion per unit volume indices from apex to base. Minor prepneumonectomy defects in the non-tumorbearing lung are likely to persist and to become worse after surgery. If the non-tumor-bearing lung is healthy preoperatively, it usually remains healthy following surgery, so that the volume and ventilation ratios remain stable. Two previously unrecognized concepts have been defined as a result of regional function studies [55]. First, a patient undergoing pneumonectomy maintains a relatively constant postoperative mechanical lung function; however, an initially disproportionate loss in lung function occurs following lobectomy that improves significantly over time [56]. This should be anticipated and planned for in the postoperative care plan. The second concept is that low perfusion in the cancerous lung is not synonymous with unresectability, although pneumonectomy is usually required because of advanced local disease. Survival rates are better for patients with the low-perfusion state in the tumor-bearing lung than for patients with a more even preoperative blood-flow distribution. The advantage of the low perfusion probably results from acclimatization of the remaining lung to the increased circulatory burden over a long period of time.

II-D. Operative morbidity and mortality

A reliable expected norm of 3.2% to 3.7% for contemporary operative mortality following lung resection has been reported in two recent studies 161-621. The patient’s age, forced expiratory volume, weight loss, coexisting disease, stage of disease and extent of the resection have been identified as significant risk factors (Tables 5 and 6). Most authors conclude that major resections can be performed with acceptable mortality in elderly patients; however, careful attention must be paid to preoperative selection, because the incidence of complications increases with advancing age, particularly after age 70 years. A recent report of mortality and morbidity risk factors for patients undergoing pneumonectomy documented an operative death rate of 7% in 197 patients [63]. Significant risk factors included the side of the operation and the extent of the resection. Patients undergoing right pneumonectomy had a significantly higher

TABLE

5

Lung Cancer

Study Group

mortality

data for pneumonectomy.

lobec-

tomy. and lesser resections Deaths Procedure

Resections

number

percent

Pneumonectomy

569

44

7.7

Lobectomy

1058

35

3.3

Lesser resection

143

2

1.4 I

p < 0.001’

Exercise oxygen-consumption measurements.

The intermediate risk group represents a wide spectrum of ventilatory impairment and includes patients who are borderline candidates for operation. Although questions remain regarding the pathophysiologic mechanisms responsible for abnormal exercise-oxygen consumption measurements, MVo2, this testing has shown promise as a criterion for predicting postoperative morbidity as well as mortality [57]. Differing results have been reported; however, the strongest predictability of postoperative outcome is reported for studies in which subjects exercise to their maximum capacity, VoZmax; patients without complications have a significantly higher Vo2max than those experiencing complications [58,59]. It is suggested that Vo2max identifies abnormal oxygen transport, which is related to postoperative morbidity and mortality. Slinger [60] reports that exercise capacity may be the most specific predictor of post-thoracotomy cardio-respiratory complication, and that stair-climbing capacity correlates with maximum voluntary ventilation. He notes that a patient who can climb two flights of stairs without difficulty can usually tolerate even a pneumonectomy without problem.

I p = N.S.”

(segmentectomy

or

wedge excision) “Chi-square

test

bN.S., not significant. From:

Ginsberg

surgical

RJ, et al. Modern

resections

in lung cancer.

thirty-day J Thorac

operative Cardiovasc

mortality

for

Surg 86; 654,

1983 (with permission).

TABLE

6

Age-adjusted

morbidity

according

to decade (1076 patients) Major complications

Age b-4 < 50

3.0

50-59

10.7

6&69

13.0

lo-79

24.5

2 80

20.0

and death %

p < 0.001

From:

Deslauriers

J, et al, Current

with elective surgical 1989 (with permission).

resection

operative

for lung cancer.

morbidity

associated

Can J Surg 32:3355339,

192

operative mortality, 12%%,than patients having a left pneumonectomy, 1%. A 15% operative mortality rate was documented for patients undergoing chest wall resection and extrapleural pneumonectomy compared to 5% for simple or intrapericardial pneumonectomy. Patients with a predicted postoperative function of FEVi > 1.65 L or FEVr > 58% of the preoperative value and an FVC (forced vital capacity) > 2.5 L or FVC > 60% of the preoperative value had a significantly lower operative mortality than patients with lower values. In this study patient age was not a significant factor in operative mortality; however, others have reported a significantly higher risk of operative morbidity and mortality for patients > 60 or > 70 years old [61,62]. Patients requiring prolonged ventilation (longer than 48 h) had a mean percent predicted FEVi of 45% of normal and a mean percent predicted FVC of 4596, whereas values were 48% and 52%, respectively, for patients on assisted ventilation for 48 h or less (p < 0.05). Atria1 arrhythmias were the most common complication, occurring in 23% (46/197) of the patients. Cardiac failure developed in 9% (18/197). Motta and Ratto [64] confirmed that operative mortality was significantly associated with the extent of the resection. They also documented a significant correlation between (i) the incidence of bronchopleural fistula or cardiac rhythm problems and the extent of resection and (ii) the frequency of atelectasis or intrapleural air spaces and the severity of the obstructive pulmonary disease. I am persuaded that morbidity and mortality following pulmonary resection can be minimized by thorough preoperative physiologic assessment of the patient, technical precision during the intraoperative period, and immediate attention to any problems. Patients at higher risk for operation should receive more intensive perioperative evaluation and hemodynamic monitoring to reduce this risk. These efforts should be focused primarily on the cardiopulmonary system.

The intent of the surgeon should be carefully documented for each surgical patient, because this has a significant bearing on the patient’s prognosis. The importance of evaluating the potential for complete resection of all known disease is illustrated in Fig. 7. The survival for patients who undergo apparent complete resection is significantly better than the outcome for those in whom no gross disease remains, but who have a high potential for recurrence. These patients may have evidence of residual disease in the lymph nodes, either microscopic intranodal or gross extranodal tumor, or extensive metastatic lymph node disease involving all or the most distal nodes in the dissection. Microscopic tumor in the resection margin is indicative of an incomplete resection; however, the implications of this are evidently less serious than of other manifestations of residual disease [65]. Although postoperative radiotherapy is usually recommended, the benefit of such treatment in this instance has not been proved. A very poor prognosis is observed for patients undergoing deliberately palliative procedures, and these operations are seldom performed. III-B. Stage I and stage II disease Surgery is considered potentially curative and is the treatment of choice for patients with clinical stages I and II non-small cell lung cancer. These groups represent about 25% of the lung cancer population, but account for 65% of all surgically treated patients [66]. Preoperative bronchoscopic and radiologic examinations confirm that all tumor is contained within the lung and visceral pleura. The proximal extent of demonstrable tumor is 2 cm distant from the carina or is contained % Surviving

80

60

III. Surgical treatment 40

III-A. Surgical procedures 20

The final operative decision will be determined only at thoracotomy; however, the resection that will encompass all the known cancer and preserve the maximum amount of lung tissue is the procedure of choice. Although lobectomy is the most frequently performed operation, a wide spectrum of procedures, from conservative segmental or wedge resections to the most radical procedures that require reconstruction, is well developed for specific disease presentations.

P= 2 cm), and tumor location (communicating with a segmental or subsegmental bronchus) had a significantly deleterious effect on survival. Of interest was the finding that CT, which is generally considered not to influence staging in peripheral Tl NO MO cancers, and intraoperative staging of even normal-sized lymph nodes significantly affected the out-

100

so

60

40

20

0

24

12 Months

48

36

After

60

TreatIMIt

Fig. 9. Comparison Fig. 8. Cumulative expected

proportions

of patients

to survive 5 years following

pathological

stage, M.D. Anderson

with primary

complete Cancer

resection,

Center

lung cancer according

1965-1982;

tive deaths within 30 days are excluded.

to

opera-

ing from

initial

(n = 244). From:

of segmentectomy lesion

only)

and lobectomy

for patients

Read RC, et al. Survival

for Tl NO MO non-small

with Tl

(deaths

result-

NO MO disease

after conservative

cell lung cancer. Ann Thorac 1990 (with permission).

resection

Surg 49: 391,

194

come in this series of patients. These authors concluded that deep-seated lesions and those located astride major intersegmental planes require lobectomy, but conservative resection can be used for the remainder with minimal risk of local recurrence. In contrast to these recommendations, Martini believes that any resection less extensive than lobectomy compromises the patient’s opportunity for long-term survival. Because of the high incidence of recurrence in patients who undergo conservative resection, he recommends that it should be used only as an alternative to no surgery for patients with poor ventilatory function [76]. The North American Lung Cancer Study Group (LCSG) initiated a prospective clinical trial in 1982 in which patients with Tl NO MO tumors were randomized at surgery, following intraoperative frozen section T and N staging, to undergo standard lobectomy or a lesser resection. End results are not yet available; however, Ginsberg [75] reported that only half the over 400 patients considered eligible for this study qualified at surgery to undergo either a wedge or a segmental resection. In the remainder completion lobectomy was required because of tumor location (50%) Nl or N2 disease (25@, greater-than-T1 tumor (13%) and other miscellaneous reasons (12%). As an alternative to no resection for patients with Tl and T2 NO tumors who have very poor pulmonary function, a wedge excision or, rarely, a lumpectomy may be performed. Errett et al. report survival rates to be virtually identical between lobectomy and wedge-excision groups and operative mortality and morbidity to be acceptable. They reported that postoperative radiotherapy reduced the risk of local recurrence for patients whose tumors crossed intersegmental planes [77]. Only the results of a prospective, randomized clinical trial will confirm the efficacy of limited resection for Tl NO MO disease. Until this information is available, limited resection for Tl NO MO tumors must be performed only after careful selection criteria for conservative resection, including intraoperative nodal staging, have been applied. The preliminary clinical trial observations and retrospective studies suggest that limited resection may be rational only for selected patients who have ‘clinical’ T 1 NO MO disease.

section. In 1984, we reported the first Nd:YAG lung resection in humans [78]. Since that time we have used the procedure in selected patients with severely limited ventilatory capacity who could not tolerate the extensive loss of lung parenchyma required for standard segmentectomy or lobectomy. Because of the tumor size and location, i.e., tumor crossing a fissure, these patients would have been denied surgery by conventional procedures. Using the laser, the surgeon can enucleate the tumor and preserve the maximum amount of lung tissue. Although the technique is well established - the laser seals off air passages, causes minimum bleeding, and kills cancer cells at the periphery of the tumor - the biologic benefit remains to be proved. I use mediastinoscopy whenever enucleation of a primary bronchogenic carcinoma is contemplated, and I do not proceed in the presence of N2 disease. We encountered no complications, reoperations for bleeding, or instances of lung abscess-formation or empyema in the first 25 patients undergoing the laser enucleations [79]. Ishida et al. emphasize that mediastinal lymph node metastasis is not rare in patients with tumors 1.0 to 3.0 cm in diameter and point out the necessity for lymphadenectomy to provide local control of the disease. Among 221 patients with Tl tumors, the incidence of lymph node metastases correlated with increasing tumor size (Table 7). These data emphasize the potential hazard involved in waiting to observe growth changes in solitary peripheral nodules [80]. 111-8.3. Sleeve lobectomy Bronchial sleeve lobectomy is another way to preserve lung tissue. It involves resecting of the involved right- or left-lung upper lobe and main bronchus in continuity

TABLE Incidence

7 of nodal disease by tumor sizes Tumor

Nodal status

size (cm)

Total patients

6 1.0

1.1~2.0

(n=220)

(n=8)

(n = 84)

2.1-3.0

NO

158

8 (100)

70 (83)

80 (62)

Nl

19

0

4 (5)

15 (12)

N2

42

0

lO(l2)

N3

L

0

0

(n= 129)

b

III-B.2. Laser resection The use of the neodymium: yttrium-aluminum-garnet (Nd:YAG) laser for lung-sparing operation in patients with severely compromised pulmonary function represents a new investigational treatment approach. This technique may be applied in special circumstances where enucleation of the primary is the only alternative to re-

aNumbers %gnificance:

in parentheses

32 (25) I2 (2)

are percentages.

p < 0.01.

Adapted from: Ishida T, et al. Strategy for lymphadenectomy in lung cancer three centimeters or less in diameter. Ann Thorac Surg 50: 708. 1990 (with permission).

195

and reanastomosing the two ends of the main bronchus (Fig. 10) [81]. Although the procedure was initially believed to be useful only for patients with compromised pulmonary function, survival rates and postoperative mortality and morbidity are equivalent to those reported for pneumonectomy in patients with similarly staged disease. Sleeve lobectomy as a deliberate alternative to pneumonectomy has been supported in retrospective reviews, and it is accepted as a valid treatment option for appropriately selected patients [82,83]. In a series of 93 patients with non-small cell lung tumors, sleeve lobectomy produced a cumulative survival rate of 34% and an operative mortality of 8.9% as reported by Toomes and Vogt-Maykopf [84]. Based on preliminary results of postoperative lung scans, these authors conclude that a centrally located tumor can be removed by bronchoplastic resection with minor loss of respiratory function. In another recently published series of 72 patients in whom sleeve lobectomy was performed electively, the patients selected at bronchoscopy were those whose tumor bulged from the upper-lobe orifice or microscopically invaded the main bronchus. At operation, patients were selected for sleeve lobectomy who had cancer cells in the resection margins, extrabronchial invasion of the main bronchus, or peripheral tumors and diseased nodes. The complication and survival rates, after a minimum follow-up of 1 year, were similar to

those of other large series of patients undergoing resection of lung tumors of equivalent stage [85]. III-C.

Stage IIIa disease

Surgery is a valid treatment option for selected patients with stage IIIa non-small cell lung cancer (Fig. 11A and B). This conclusion has been reached as a result of advances in surgical techniques and support technology and on the basis of survival data that show a better prognosis for patients with locally advanced tumors than might be achieved with other modalities. A lung tumor is considered technically resectable if an apparent complete resection of all known cancer can be anticipated. Apparent complete resection is defined as follows: First, the surgeon is certain that the operation has encompassed all known disease; second, the proximal margins of the resected specimen are microscopically free from tumor; third, within each major lymphatic drainage region, the most distant node is microscopically free from tumor; and last, the capsules of resected lymph nodes are intact. Although many patients undergo operation for stage IIIa disease whose resections do not meet these criteria on final pathologic evaluation, the end results are highly dependent on the foregoing factors. Patients with ipsilateral mediastinal lymph node me-

B Fig. 10. Diagrammatic Conservative

resection

representation: for lung cancer.

(A) Right

upper

sleeve lobectomy,

(B) Left upper

sleeve lobectomy.

In: Delarue NC, Eschapasse H. eds. International Trends in General Philadelphia: W.B. Saunders, 1985; 88 (with permission).

From:

Toomes

H, Vogt-Moykopf

Thoracic

Surgery.

Vol.

I. Lung Cancer.

I.

196

T3 NO MO Superior sulcus tumor d

I

T2 N2 MO L

T3 Nl MO Peripheral tumor involving chest wall and intrapulmonary lymph nodes . .

>3 cm. tumor involving ipsi lateral hilar and mediastinal lymph nodes

A

R. main bronchus

L-

Mediastinal parietal pleura -

R. pulmonary artery -2%

Esophagus

W-Trachea

\ KGB --L.

pulmonary artery

Pericardial mediastinal pleura Hilus of right lung74

Tumor involving mediastil nal pleura, pericardium and ipsi lateral mediastinal lymph nodes

Stage III -a Fig.

11. Diagrammatic

cancer.

representation:

(A) Stage IIIa disease

Chest 89 (Suppl): 225S, 1986 (with permission). tic implications

of the international

TNM

subsets.

From:

(B) stage IIIa disease - central staging

system for lung cancer.

Mountain

CF. A new international

tumor involving Semin Oncol

pericardium.

staging

From: Mountain

15: 236, 1988 (with permission).

system

for lung

CF. Prognos-

197

tastases or with extrapulmonary extension of the primary tumor and metastases confined to the intrapulmonary, including hilar, lymph nodes (the Tl-3 N2 MO and T3 NO-l MO anatomic subsets) may be selected for definitive operation. The latter group includes those with peripheral tumors that invade the parietal pleura and chest wall, superior sulcus tumors, and tumors that involve the mediastinum only minimally or the main bronchus less than 2 cm from the carina. Our results for 198 patients with stage IIIa disease who underwent definitive resection - a cumulative survival rate at 5 years of 28% - support the concept that selected patients in these categories can derive substantial benefit from surgery [311. It is well to keep in mind that the surgeon’s criteria for operation and the criteria for staging are not the same - all tumors staged IIIa are not considered amenable to complete resection. I exclude patients with evidence of metastasis to the highest mediastinal group the high paratracheal nodes in the area of the thoracic

inlet. Evidence of gross perinodal disease is a very poor prognostic sign, highly indicative of microscopic residual disease. If the extranodal disease is grossly evident when the nodes are assessed at mediastinoscopy, patients are generally excluded from surgical treatment. Pathologic examination of all mediastinal lymph node groups - i.e., superior mediastinal, aortic, and inferior mediastinal - is required to make a valid assessment of complete resection. If the highest or most distant node in the dissection is positive for tumor, the resection is considered incomplete owing to the very high probability that further occult metastatic disease is present. III-CA.

Lymph node mapping

The scheme for mapping the results of mediastinal lymph node sampling developed and tested by Naruke et al. [86] and modified by the AJCC for use with the International Staging System has been widely used [2]. In this system single-digit numbers designate mediastinal nodes (N2 disease) and double-digit numbers represent intrapulmonary, including hilar, nodes (Nl disease). The lymph nodes designated ‘hilar’ are the proximal lobar nodes within the pleural envelope and distal to the mediastinal pleural reflection (Fig. 12A). The staging committee of the American Thoracic Society (ATS) has proposed a classification for mediastinal lymph nodes in which nodal ‘stations’ are related to radiologically identifiable anatomic structures (Fig. 12B) P71. EtlACHlOCEPHAllC

LSUEClAVlAN ARTERY

----me

,------AORTA

N2 Nodes -Superior

Nl Nodes Medlasl~nal

1. Highest

Medlashnal

10

Hllar

11

lnlerlobar

Upper Paratracheai

12

Lobar

3. Pre- and Relrotracheal

13

Segmental

2 4

l

Nodes

Lower Paratracheal imcludmg Azygos Nodes)

Aorttc Nodes 5

Subaortx

6. Para-aOrilc

(aorttc

A

wmdow)

(ascendmg

aorta or

phremc) l

lnferlor

Medraslmal Subcannal

8 9

Paraesophageal (below carma) Pulmonary Ligament

Fig. 12. Classification Cancer

Nodes

7

of mediastinai

(from: Beahrs OH, Henson

and (B) the American

Thoracic

and intrapulmonary DE, Hutter

Society.

lymph

nodes according

RVP, Myers MH, eds. Manual

See Appendix

for details and anatomic

to recommendations

for Staging definitions

of Cancer.

of (A) the American Philadelphia:

of each nodal station

Am Rev Resp Dis 5: 659, 1983 (with permission).

Joint Committee

J.B. Lippincott, (from: American

on

1988; 12&121), Thoracic

Society.

198

With the exception of the designation for ‘hilar’ lymph nodes, station 10 in the scheme recommended by the AJCC, the two classifications are fairly similar. The ATS recommendations include descriptions of the specific anatomic structures that limit each nodal station; these structures are identifiable radiologically, at mediastinoscopy and at thoracotomy. The AJCC scheme is a simpler categorization based on standard anatomic definitions for each lymph node group, i.e., superior mediastinal, aortic, inferior mediastinal, and intrapulmonary, including hilar. I am presently studying the utility and the implications for clinical and surgical staging and for survival of the nodal stations defined in both classifications. The study includes a series of 2000 patients who have undergone treatment for primary lung cancer in the last 6 years. Because the definitions of nodal stations are not entirely consistent, it is very important that radiologists, surgeons, and pathologists specify the nodal mapping scheme used to classify the lymph nodes and designate the anatomic locations of nodes reported as intrapulmonary, Nl, and mediastinal, N2, lymph nodes. The same nomenclature should be used for clinical, pathologic and retreatment staging. III-D.

TI-3

N2 MO disease

The most controversial questions regarding resectability relate to the presence of mediastinal lymph node metastasis. Some physicians consider clinical evidence of mediastinal adenopathy a contraindication to operation [39], and others exclude selected patients with positive nodes identified at mediastinoscopy [88]. My most recent retrospective report included 118 patients with N2 disease who underwent complete resection [3 11.The outcome for patients in this group who had squamous cell carcinoma was superior to that for adenocarcinoma and large cell carcinoma, as it was for the patients in every subset of stage IIIa disease. Twenty-nine percent of the patients with squamous cell tumors, compared to 14% of the patients in the adenocarcinoma and large cell carcinoma group were expected to survive 5 years or more. The survival curve for the two major cell type groups was similar at 15 months following operation; however, after this point, fewer failures occurred in those with squamous cell tumors (Fig. 13). Although the survival rate for patients in the adenocarcinoma and large cell carcinoma subset is lower, I still believe that surgery can offer greater benefit for good-risk patients than might be achieved by other treatment modalities. Other investigators have not shown this disparity in outcome between patients with squamous cell carcinoma and adenocarcinoma [89]. Ishida et al. recently reported an 18% 5-year survival

% Survivina

OL0

12

24 Months

After

36 Treatment

Fig. 13. Cumulative

proportions

3 N2 MO non-small

cell lung cancer expected

ing complete

resection,

according Center,

of patients

46

with pathologic

t

D

stage Tl-

to survive 5 years follow-

to cell type (M.D. Anderson

Cancer

1965-1982).

rate for 115 patients with N2 disease who underwent resection [90]. Factors that showed a statistically significant influence on the outcome were curative or noncurative operative status, intranodal or extranodal invasion, the grade of nodal metastases (microscopic, moderate or gross metastatic involvement of the nodes) and the T status (Table 8). Postoperative irradiation had no significant effect on the survival rate. Multiple sites of mediastinal lymph node involvement have a more adverse effect on prognosis than does the particular site of metastases, e.g., subcarinal versus paratracheal [91]. Maggi et al., made a similar observation in a retrospective review of 1103 thoracotomies that included 236 patients with N2 disease [92]. In their series, 57.2% (157/236) of patients with ipsilateral mediastinal lymph node metastasis who underwent curative resection achieved an overall 5-year cumulative survival rate of 23.1%. Patients with mediastinal metastasis limited to the upper mediastinal lymph nodes (paratracheal and aortic nodes) had a better outcome, 27.8% surviving at 4 years, than patients with both upper and lower mediastinal metastases, 9.1% surviving at 4 years. This difference was statistically significant. Skip’ metastases were present in 13% of the patients with N2 disease - no evidence of intrapulmonary or hilar nodal metastases was found; however, over 50% of the patients with hilar lymph node metastasis also had N2 disease. In a recent commentary, Shields emphasized that the results of surgery for patients with N2 disease are based on the surgeon’s criteria for selection of patients for operation [93]. He believes that metastasis of a non-small

199

tastases

TABLE

8

Surgical

treatment

of local disease,

of N2 disease % Surviving

Factor

26%

Curative Noncurative

9%

l-

5 years

surgical

trial of surgical

p < 0.01 I

11%

amycin),

-c

41%

Moderate

p < 0.01 16%

18%

Overall Definitions:

Curative,

tomy plus complete all N2 disease; section

primary

removed

systematic

noncurative.

or incomplete

resection

not

metastatic

foci in N2 nodes less than

Adapted lymph

mediastinal

macroscopically;

lymph

disease.

Microscopic,

moderate,

macroscopic

10 mm in diameter;

of

node dis-

gross, meta-

10 mm.

from: Ishida I, Tateishi

treatment

or pneumonec-

lymph node dissection

with residual

metastasis

stasis exceeded

recognized

by lobectomy

mediastinal

incomplete

of patients

M, Kaneko

with nonsmall-cell

node involvement.

J Surg Oncol

adjuvant

cisplatin)

regimen

tients with Stage II/III

6%

Gross

or

randomized

chemotherapy

clinical

for non-small

cell lung cancer was reported by the LCSG. [95] The CAP (cyclophosphamide (Cytoxan), doxorubicin (Adri-

Metastasis p i 0.01

irradiation,

treatment.

III-D.1. Adjuvant therap_v The first positive, prospective,

34%

Extranodal

- by surgery,

p < 0.05

Invasion Intranodal

however

are sure to follow. Control

combined treatments - does not influence the devastating effects of the occult distant metastasis present at the time of operation in the majority of patients who fail

Operation

Microscopic

and other problems

S, Sugimachi

lung cancer

K. Surgical

and mediastinal

43: 161. 1990 (with permis-

sion).

cell bronchial carcinoma to the ipsilateral mediastinal lymph nodes must be considered an ominous progression of the disease process and that surgical treatment is applicable for only a small subset of patients with N2 disease. He notes, however, that it is important to identify those patients who may benefit from surgery: patients with clinically unrecognizable N2 involvement, with N2 disease discovered at mediastinoscopy (intact nodal capsule; low paratracheal, superior tracheobronchial, or aortic window or subcarinal disease; involvement of only one node and the absence of fixation) or with N2 disease discerned at thoracotomy for a proposed resection. Patients undergoing apparent complete resection for stage IIIa-N2 disease are primary candidates for adjuvant therapy. Traditionally, most patients with mediastinal lymph node metastases have been referred for postoperative radiotherapy. This treatment has proved effective in controlling local recurrence, but results have not translated to an improved survival rate [94]. These findings do not imply that adjuvant irradiation is of no value; if local recurrence is not controlled, distant me-

was evaluated

completely

in 130 pa-

resected adenocarcin-

oma and large cell carcinoma. The chemotherapytreated patients had a significantly longer disease-free interval following resection, 7 months, than the control group (who received immunotherapy) p= 0.018; however, a significant survival advantage for the chemotherapy-treated patients was not shown. Updated reports note that failure continues to occur in the chemotherapy arm of the study but significantly less often than in the non-chemotherapy arm [96]. The effectiveness of a regimen of postoperative chemotherapy and radiotherapy for patients with incompletely resected stage IIIa disease has also been reported by the LCSG [97]. One hundred and seventy-two patients were randomized to receive either postoperative irradiation or postoperative irradiation plus chemotherapy with the CAP regimen. Patients assigned to the postoperative chemotherapy/radiotherapy arm of the study had a significantly longer recurrence-free survival than patients receiving radiotherapy only. p = 0.004. The distant-recurrence rate was significantly less for the group receiving the combined postoperative treatment, p= 0.01. Encouraging results of a feasibility study of perioperative therapy for patients with N2 disease were reported by Martini et al. in 1988 [98]. These investigators treated 41 patients who had clinical N2 MO non-small cell lung carcinoma with two or three cycles of high-dose cisplatin plus vindesine (or vinblastine sulfate) with or without mitomycin-C. Thoracotomy was performed in 28 of the 30 patients who achieved a radiographically documented major response; 21 (75%) of patients had complete resections; tumor sterilization was proven histologically for eight patients; and those who underwent a complete resection achieved a 54% survival rate at 3 years. An updated, unofficial report has noted that the results were similar for an enlarged group of 68 patients [99]. This study showed that: (i) available combination chemotherapy is effective in producing a major tumor

200

regression in patients with N2 disease; (ii) complete resection is feasible and can be accomplished in the majority of patients, and (iii) initiation of a large-scale, randomized study to assess the potential of preoperative chemotherapy for patients with N2 disease is rational. Not all investigators have achieved positive results with adjuvant combination chemotherapy. Whether the differences in results are related to drug dosages, drug combinations or drug sequencing is not clear; however, the need for using the most effective regimens is emphasized. Dautzenberg et al. [ 1001reported failure of the perioperative PCV (cisplatin, cyclophosphamide, vindesine) treatment regimen for patients with resectable nonsmall cell carcinoma. Significant disease progression in 45% of the patients and a high incidence of metastases indicated that the chemotherapy was ineffective and patient entry into the study was discontinued. At the M.D. Anderson Cancer Center we are pursuing investigations of pre- and postoperative adjuvant chemotherapy for patients with stage III non-small cell lung cancer. Currently we are comparing induction chemotherapy using the CEP regimen (cyclophosphamide (Cytoxan), etoposide (VP- 16) and cisplatin - three preoperative cycles, followed by restaging and surgery in operable patients, followed by three postoperative cycles for patients who respond to the induction regimen) to surgery alone. In another study, patients found at thoracotomy to have mediastinal lymph node metastases are randomly assigned to receive either six postoperative courses of chemotherapy with CEP plus chest irradiation (50 Gy) and brain irradiation (30 Gy) or postoperative observation only. In a third study, patients who undergo incomplete resection are randomized to receive postoperatively either six courses of CEP, chest irradiation (56-60 Gy for microscopic residual disease, 6&66 Gy for gross residual tumor), and brain irradiation (30 Gy) or only postoperative chest irradiation (according to the above plan). III-D.2. Surgical procedures The surgical procedure for patients with N2 disease, identified either at mediastinoscopy or at thoracotomy is tailored to encompass the primary tumor and all involved lymph nodes: the dissection is continued until all nodes are removed or the most distant nodes in the dissection are negative on frozen-section biopsy. ‘Pneumonectomy’ may be required to completely remove tumors that involve hilar structures or that have metastasized to more than one mediastinal area. The advantage of the pneumonectomy is that it is able to completely remove any occult disease that may be present in non-tumor-bearing lobes and lymphatics. It is a very effective treatment, when it is required; refinements in sur-

gical technique, the use of stapling devices and of perioperative antibiotics have lessened the occurrence of the major complications, bronchopleural fistula and empyema. The disadvantages of pneumonectomy are an increase in operative risk, particularly when tumors are in the right lung or when patients are elderly, and an increased incidence of major complications. For these reasons, and because the efficacy of lesser procedures has been documented, pneumonectomy is avoided whenever possible. When tumors invade the pericardium or involve the lymph nodes surrounding the major vessels, ‘radical pneumonectomy’ may be performed. This operation involves intrapericardial dissection and ligation of the vessels. It is encouraging that some improvements in prognosis have been shown for selected patients undergoing operation for stage III-N2 disease; however, the major problem of distant failure, and in particular the occurrence of brain metastases, even when surgery is intended to be ‘curative’ has not been resolved. III-E.

T3 NO-N1 disease

Patients with peripheral tumors invading the chest wall, tumors originating in the superior sulcus of the lung, tumors minimally involving the mediastinal pleura and pericardium, with and without intrapulmonary lymph node metastases, and tumors less than 2 cm from the carina are included in the T3 NO-N1 subsets. Although extensive resections may be required, selected patients in these categories derive significant benefit from surgical treatment. The criteria for patient selection relate to factors of technical resectability and to the extent of regional lymph node metastases. In our experience at the M.D. Anderson Cancer Center, 39% of 80 patients who underwent complete resection for T3 NO-N1 tumors were expected to survive 5 years or more. Patients with squamous cell carcinoma had a better outcome than those in the adenocarcinoma and large cell carcinoma group: cumulative 5-year survival rates were 49% and 26%, respectively (Fig. 14). The tumor location did not significantly affect the outcome; cumulative survival rates were 39% for patients with peripheral tumors invading the chest wall, 32% for those with tumors originating in the superior sulcus, and 41% for patients with other extrapulmonary extension of the primary tumor [3 11. III-E.1.

Superior sulcus tumors

Patients with tumors originating in the superior sulcus of the lung who are selected for operation usually have no clinical evidence of invasion of the vertebral body or major mediastinal organ or evidence of

201

regional tumor control was 52%, whereas for those with local failure it was 12.5%, p-C 0.00001. Ricci et al. reported a 34% actuarial 5-year survival rate for 22 patients with superior sulcus tumors who underwent preoperative radiotherapy and radical (curative) resection [104]. They treated a total of 56 patients; 19 had nonradical resections and 15 were treated with radiation only. Lymph node status was an important prognostic factor; an actuarial 5-year survival rate of 38.1% was shown for patients with no lymph node metastases, 14.3% for those with Nl, and 0% for those with N2 disease.

% Surviving

0'

12

0

24 36 Months After Treatment

Fig. 14. Cumulative

proportions

NO-1 MO non-small

cell lung cancer

lowing

complete

resection, Cancer

of patients

according Center,

48

with pathologic

expected

to survive

to ccl1 type (M.D.

60

stage T3 5 years folAnderson

1965-1982).

Horner’s syndrome. There may be involvement of the transverse process or a lytic lesion of the rib that can be encompassed by the dissection. Superior sulcus tumors are removed through an extended resection involving the upper lobe, chest wall, and lower brachial plexus. Because of the location of the tumor and the nature of the operation, a degree of postoperative neurologic deficit - loss of ulnar nerve function and sensory innervation of the inner aspect of the upper arm usually occurs [ 1011. According to the recommendation of Paulson [102], and based on his results, patients with superior sulcus tumors have been treated empirically (and almost universally) with preoperative radiation, usually 30 Gy; however, there is no scientific proof that preoperative radiotherapy is of significant benefit in this clinical situation. Komaki et al. reviewed several treatments and clinical factors related to the outcomes of 85 patients with superior sulcus tumors treated at M.D. Anderson Cancer Center from 1977 through 1987. Included were 25 patients whose surgery was part of a comprehensive treatment plan [103]; 24 patients received adjuvant irradiation, preoperatively, postoperatively, or both. The 2year survival rate for the patients whose disease extent permitted resection, was 52% (13/25) as compared to 22% (13/60) for those whose treatment plan did not include surgery, i.e., those who received radiotherapy, with and without chemotherapy or chemotherapy alone. Control of the local tumor was a significant prognostic factor: the 2-year survival rate for patients with local-

III-E.2. Peripheral tumors involving chest wall Chest wall pain is the predominant presentation in patients with peripheral tumors involving the chest wall. En bloc resection of the lung tumor and involved structures, with reconstruction, if required, is the treatment of choice for patients who meet resectability and operability criteria. The operation will include a block portion of the ribs and intercostal muscles over the tumor, and the extent of the resection, which includes about a 4-cm tumor-free margin, is determined according to the specific disease presentation. The favorable prognosis for patients undergoing chest wall resection and the implications of lymph node metastases are reflected in the survival rates; our cumulative survival rates as documented at 5 years were 38% for all patients and 47% for those with no lymph node metastases. Most authors agree that the status of the lymph nodes, not the chest wall invasion, is the key factor in survival. The following reports confirm this observation and suggest the utility of mediastinoscopy prior to chest-wall resection. In one report, 54% of the patients with T3 NO MO tumors, but only 7% of those with T3 Nl-2 MO disease, survived 5 years [105]; in another series one of six patients with Nl disease and none with N2 survived 2 years [ 1061;and in another, the 5-year actuarial survival rate was 56% for patients without lymphatic metastases and 21% for those with lymph nodes involved [ 1071. There is some disagreement over the extent of resection required for patients with peripheral tumor invasion that is apparently limited to the parietal pleura. Grill0 recommends that, if cure is to be obtained, any (parietal pleura) evidence of chest-wall involvement requires full-thickness resection of the wall around the area of involvement [108]. McCaughan et al., however, prefer to attempt an extrapleural dissection, and, if they can readily achieve a tumor-free plane, they limit the resection to extrapleural [107]. These authors report a 62% survival rate for 54 patients with no lymph node involvement. When tumor is found or suspected beyond

202

the parietal pleura, they perform chest-wall resection. My approach is the same as that of McCaughan and colleagues. In my experience, patients with squamous cell carcinoma who undergo chest wall resection have a better outcome than those with adenocarcinoma, but the difference in the survival rates is not statistically significant. I have also observed better results for patients younger than 60 years than for those older; 50% and 215&,respectively, were expected to survive 5 years [31]. Defects of the chest wall for which primary closure of the skin is possible can be very satisfactorily reconstructed using Marlex mesh or Goretex [ 1091. Some surgeons believe that Marlex is associated with a high incidence of postoperative infection; however, this has not been my experience. With proper care, in the absence of pre-existing infection of the skin or chest wall, no morbidity should result from the use of Marlex or Goretex. A recent evaluation of our experience with chest-wall resection, under the circumstances just stated, revealed no instances of major infection and no need for reoperations. Excellent relief of pain was reported by Warner et al. in a series of 11 patients who underwent concomitant resection of the lung and chest wall [ 1lo]. They also observed that patients with squamous cell carcinoma had the best outcome, that chest wail prosthesis was seldom needed, and that survival was related to the status of the lymph nodes. III-F. Other bronchoplastic procedures

Extended operations for tumors involving mediastinal structures, T3 and T4 disease, have been refined. Tracheal-sleeve pneumonectomy, usually performed for carcinomas of the right upper lobe that locally infiltrate the trachea, was formerly associated with unacceptable operative mortality; however, in a recent report Darteville documents a 10.9% operative death rate among 55 patients undergoing this procedure [ 1111. Thirty-eight percent of patients survived 3 years, and 23% 5 years following operation. The author concludes that trachealsleeve pneumonectomy is now fully justified for selected patients. Patients whose upper mediastinal lymph nodes are involved and those with tumors involving more than 2 cm of the distal trachea are excluded. Naruke [112] notes that bronchoplasty to preserve pulmonary function, enhance curability, and extend the scope of operative indications is particularly applicable for patients with squamous cell carcinoma or low-grade malignancy. Tracheobronchial resection and reconstruction for tumors involving the tracheal carina is also applicable for a few patients; with experience and appropriate selec-

tion, this operation can benefit some patients, providing a survival duration that is equivalent to that achieved for patients with other presentations of stage IIIa disease [ 1081. Grill0 [ 1131cautions, however, that resection of the tracheal carina for lung cancer carries with it a threat of much higher morbidity and mortality than does a simple pneumonectomy. Patients should be very carefully selected for such an operation and the operations should be performed only by surgeons familiar with bronchoplastic and tracheoplastic techniques. Lung cancer that invades mediastinal vascular structures, such as the aortic arch and superior vena cava has long been considered inoperable. However, Nakahara et al. report that, by applying developments from cardiovascular surgery such as polytetrafluoroethylene grafts, an experienced staff can safely perform extended operations that combine resection and reconstruction of these vessels with tracheal-sleeve pneumonectomy or lobectomy [114]. Among six patients who underwent extended operations for lung cancer that invaded the aortic arch and superior vena cava, two remain alive 17 and 34 months following surgery and four have died at 4, 5, 12 and 18 months after operation. In addition, a 5-year survival has been reported for a patient who underwent resection of the superior vena cava with tracheal-sleeve pneumonectomy for primary lung cancer [115]. These procedures are investigational and can only be attempted by those trained and experienced in the techniques. The balance between what is biologically rational and what is technically feasible is an important consideration. IV. Patterns of failure

The limits of surgical cure are reflected in survival patterns by stage (Fig. 15). Surgery for stage I disease is very effective; a 60% 5-year survival rate can be expected. For patients in the stage II and IIIa categories, survival rates of 32% and 28%, respectively, can be achieved. Median survival durations for each of the stage groups, shown in the legend for Fig. 15, dramatically illustrate the enormous impact on survival of enlarging tumor size, lymph node involvement, and extrapulmonary extension. These end results and those from other studies according to stage and cell type show that the failure ‘rate’ following apparently curative resection is directly related to the extent of the cancer. It differs according to cell type, if the level of disease extent is greater than stage I. Curative surgery fails to cure because of occult metastatic disease that cannot be identified prior to operation. In our series of 745 consecutive patients undergoing complete resection at M.D. Anderson Cancer

203

% Surviving

TABLE Pattern

9 of first observed

failure following Regional

curative

onlyb (s)

surgery”

DistantC

or distant

and

regionaId (SK;) stage I

31.5

68.5

II

21.8

78.2

IIIa

14.8

85.2

carcinoma

21.9

78.1

Adenocarcinoma

25.7

74.3

0

100.0

24.1

77.9

40 Cell Type Squamous (n=199)

20 P=

Surgical treatment of lung cancer.

Critical Reviews in OncologylHemalology, 1991; 11: 179-207 8 1991 Elsevier Science Publishers B.V. AII rights reserved. 1040-8428/91/%3.50 ONCHEM 17...
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