Lung cancer in elderly patients

Lung cancer in elderly patients

Jamie C. Hey, MDUniversity of Maryland School of Medicine, 10 South Pine Street, Suite 800,

Baltimore, MD 21201, USA

Lung cancer is the most deadly malignancy in men and women in the United

States [1]. The incidence of new cases rose steadily throughout much of the 1900s

after the development of the commercial cigarette market. Only recently has the in-

cidence of new cases in men begun to fall [1]. This trend has not been seen in

women because their increased cigarette use came much later than that in men. The

cause of most lung cancer is long-term exposure to cigarette smoke; therefore, this

is a disease in adults. The risk of developing lung cancer rises with age and, al-

though there may be a rising incidence of adenocarcinoma in younger adults, most

patients with lung cancer are older than 50 years and more than one third are older

than 65 years [2].

Physicians caring for elderly patients with lung cancer are often faced with dif-

ficult decisions. The difficulties arise for at least two reasons. First, lung cancer that

is clinically apparent is not indolent. Prostate cancer is much more common than

lung cancer in the elderly male population but is less likely to be the cause of death

in a given patient [1]. Thus, there is more impetus to offer treatment to the patient

with lung cancer than with some other malignancies. Second, the treatments are all

associated with significant morbidity. Thoracic surgery with pulmonary resection,

systemic chemotherapy, and even localized radiation therapy all have the potential

to cause significant morbidity and even mortality. These points are made to under-

score the importance of a careful, thorough approach to the lung cancer patient, not

to advocate withholding treatments. There is much literature citing the ability of

appropriately selected elderly patients to tolerate surgical and nonsurgical treat-

ments for lung cancer. These treatments are known to improve survival and quality

of life and should be offered whenever possible. The details regarding risks of treat-

ments in elderly patients are discussed later. The general approach to diagnosis,

staging, and treatment of lung cancer does not vary based on age and the following

discussion is applicable to all patients. Risk assessment and cost-benefit analysis

are performed in every case. Most patients with lung cancer have some amount of

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Clin Geriatr Med 19 (2003) 139–155

cardiovascular and pulmonary disease regardless of age because of their smoking

history. The careful staging of the cancer and the severity of the cardiopulmonary

limitations much more than patient age determine what treatment is delivered.

Fortunately, older patients with lung cancer tend to be diagnosed at an earlier stage

than younger patients [3]. O’Rourke et al [2], in a large-scale retrospective analysis,

found that the percentage of cases of local disease in patients younger than 54 was

15% compared with 25% in patents older than 75. This finding further supports the

appropriateness of aggressive treatment evaluation in these older patients. Whether

the mechanism for this important difference between the younger and older age

groups is related to tumor biology or increased surveillance is unknown.

Cell types

There are many different types of malignancy that can develop in or

metastasize to the lung. When physicians and the general public discuss ‘‘lung

cancer,’’ they are referring to bronchogenic carcinoma, which includes the

categories of small-cell lung cancer (SCLC) and non-small-cell lung cancer

(NSCLC), both of which are caused by cigarette smoking in most cases. The

other primary lung cancers, including bronchial gland tumors, carcinoid tumors,

and vascular sarcomas, are rare tumors in comparison to SCLC and NSCLC and

are not discussed here. NSCLC accounts for most lung cancer and includes

squamous cell carcinoma and adenocarcinoma. Over the past several decades

there has been a shift in the distribution of histology away from squamous cell

carcinoma toward adenocarcinoma, which is now the most common type of lung

cancer [4,5]. This shift may be related to changes in cigarettes, such as the

presence of filters and the lowering of tar and nicotine contents [6]. Adenocarci-

noma is more common in women than men and is the most common histology

seen in the rare nonsmoker with lung cancer [7]. There are some differences

between cell types of NSCLC in presentation and course. Adenocarcinoma is

more likely to have metastasized at the time of presentation than is squamous cell

carcinoma and some physicians recommend more aggressive radiographic

staging for the former [8,9]. Overall survival and treatment approach is not

different between the subsets of NSCLC [10,11]. SCLC accounts for approx-

imately 20% of all lung cancer and is in the advanced stage at presentation in

more than half the cases [12,13]. The incidence of SCLC may fall with increasing

age whereas that of squamous cell carcinoma rises [14]. The chance of cure in

SCLC is low, but there has been improvement in survival with advancements in

chemotherapy over the last several years [15].

Diagnosis and screening

Although lung cancer is occasionally diagnosed incidentally by radiograph

performed for a nonrelated reason, most cases present with symptoms. The

J.C. Hey / Clin Geriatr Med 19 (2003) 139–155140

presentation may relate to local tumor invasion, such as chest wall pain or

hemoptysis, shortness of breath from a pleural effusion, or lobar collapse, or to

systemic complaints such as weight loss. Most cases of symptomatic lung cancer

are at a locally advanced stage at the time of diagnosis.

There long has been an interest in screening for lung cancer. The benefit seems

obvious. Patients with early-stage disease have a longer survival period than

those with advanced stage; thus, increasing diagnosis of early, asymptomatic

tumors should improve overall survival. In addition, not everyone needs to be

screened, such as they are for breast or prostate cancer. The focus could be on

smokers who account for almost all cases of lung cancer. Screening could be

narrowed further to include only those smokers with the highest risk profile, such

as older patients with smoking-related chronic obstructive pulmonary disease

(COPD) [2,16]. Given the large number of smokers in the United States this

would still represent a major health care expenditure. There is currently no

official recommendation for lung cancer screening in any group. If the at-risk

group is easy to recognize and the early-stage cases have improved survival, why

is screening not part of the standard practice? The reason is that there have been

no definitive data supporting the ability of screening to decrease mortality. This is

not for lack of research. In the 1970s there were three large-scale prospective

studies of lung cancer screening using chest radiographs and sputum cytology

[17–19]. The interpretation of all three was similar; screening did not improve

overall mortality. Proponents of screening long have argued that the studies were

flawed in several ways. First, two studies assessed the role of sputum cytology in

addition to routine chest X-ray. Thus, the control groups were being screened by

chest X-ray. Therefore, although it is commonly stated that routine chest X-rays

in smokers do not improve mortality, this issue has never been well researched.

Routine chest X ray and sputum cytology did lead to an increase in lung cancer

diagnosis and a shift to earlier stage at time of diagnosis. Second, the study

population included smokers older than 50 years. A higher risk population

defined by abnormal pulmonary function and more advanced age may be

impacted differently by screening.

The debate over lung cancer screening has increased recently with the

introduction of low-dose spiral CT scanning as a new screening tool. CT scanning

is more sensitive than chest X-ray or sputum cytology for diagnosing lung cancer.

Henschke et al [20] reported on CT screening in 1000 smokers at least 60 years of

age. The baseline screening CT revealed nodules in 23% of patients with a

prevalence of malignancy of 2.7%. Chest X-ray detected only 7 of 27 cases of

cancer. This approach has gained popularity in the community and larger studies

are ongoing; however, before CT becomes a recommended and reimbursed

screening tool large-scale studies will need to show improved survival without

undue morbidity from the evaluation of benign nodules that make up most CT

scan abnormalities.

Even without screening clinicians are certainly familiar with the presentation

and evaluation of the solitary pulmonary nodule. Because most lung cancer is

advanced at presentation and diagnosis is not often difficult, the best approach in

J.C. Hey / Clin Geriatr Med 19 (2003) 139–155 141

these patients is to make a definitive diagnosis at a site of tumor spread, thus

staging the patient at the same time. The patient with a large effusion therefore

may only need a thoracentesis to diagnose the cancer and prove advanced

T4 disease. Similarly, a patient with lung and adrenal masses likely has metastatic

stage IV lung cancer and the first procedure should be a needle biopsy of the

adrenal gland. Sputum cytology can also be helpful in the patient with a central

tumor and sputum production or hemoptysis. This is the only noninvasive way to

make a diagnosis.

Early-stage disease presents more of a dilemma. Limiting the morbidity of

biopsy procedures is important, but assuring resection of early tumors is the

priority. Thus, suspicious lesions in at-risk patients usually need an invasive

evaluation. CT characteristics such as calcification pattern or destiny are rarely

reliable enough to make a benign or malignant diagnosis certain. The options for

further evaluation traditionally include surgical resection of the nodule, invasive

biopsy, or observation with serial CT scans. Surgical resection is the only

approach with absolute accuracy. Biopsy procedures, including bronchoscopy

with transbronchial needle aspiration (TBNA) and CT-guided transthoracic

needle aspirates provide useful information when positive for malignancy. An

additional benefit of bronchoscopy is the ability to perform diagnosis and staging

in the same setting using TBNA of mediastinal and hilar lymph nodes.

Unfortunately, needle biopsies rarely provide strong enough evidence for a

benign diagnosis to preclude further evaluation. Thus, some experts advocate a

surgical approach to pulmonary nodules in patients at risk for lung cancer,

arguing that no other approach has a high enough specificity given the deadly

natural history of unresected carcinoma. If a negative result on needle biopsy

leads to surgical resection because malignancy hasn’t been reliably ruled out and

surgical resection is the treatment of choice if the biopsy is positive, why bother

with the needle biopsy?

There are several reasons why some centers continue to advocate nonsurgical

biopsy procedures in all cases in which they can be performed safely. First, the

physician must consider the surgical procedure to be undertaken for diagnosis. If

there is no diagnosis at the time of surgery the first procedure will usually be a

wedge resection of the nodule with frozen section analysis by a pathologist. It

would be detrimental to the patient to perform a larger procedure, such as a

lobectomy for what could be a benign lesion or to perform separate biopsy and

resection operations. If the frozen section analysis reveals malignancy the

appropriate cancer operation is then completed. In a patient with good cardio-

pulmonary reserve, this requires at least a lobectomy. If the sample is benign no

further resection is necessary. The reliability of frozen section analysis is critical

in this situation. There are several possible outcomes from the procedure based

on surgical findings and pathology. This preoperative uncertainty is difficult for

many patients faced with the possible diagnosis of lung cancer. A preoperative

biopsy that confirms the diagnosis allows appropriate treatment planning and

patient education. Occasionally an early tumor is found to be an SCLC on

biopsy. There are few reports of long-term survival after resection of early-stage


small cell carcinoma and the standard treatment for limited-stage disease

remains combination chemotherapy and radiation. Finally, there is the important

issue of staging. As discussed later, staging of mediastinal lymph nodes is

crucial in treatment planning for lung cancer. Recent treatment advances have

involved more preoperative chemotherapy and radiation for cases with lymph

node spread necessitating accurate preresection mediastinal staging. CT scanning

is relatively insensitive for diagnosing mediastinal lymph node metastasis.

Surgical staging with mediastinoscopy has been recommended by some physi-

cians for all cases prior to surgical resection. Again, to perform a staging

procedure followed by a pulmonary resection without confirming the diagnosis

of lung cancer by needle biopsy may be overly aggressive and difficult for

patients to accept.

The flexible bronchoscope is an indispensable tool in thoracic oncology.

Bronchoscopy is universally used in diagnosis, staging, and treatment of lung

cancer. Flexible bronchoscopy is routinely performed under conscious sedation

with very low risk of significant complications. Rigid bronchoscopy is performed

under general anesthesia in most instances and is reserved for palliative resection

of bulky endobronchial tumors. Diagnosis and staging begin with visual

examination of the airways including the larynx. A patient with a left upper

lobe mass and hoarseness of voice is likely to have impingement of the recurrent

laryngeal nerve by malignant aortopulmonary lymph nodes. Paralysis of the left

vocal cord will be noted in this situation and a TBNA of those nodes should be

performed for confirmation. Examination of the lower airways may reveal an

endobronchial tumor and the exact location of the tumor is crucial in staging. If

no endobronchial component is seen a biopsy can be performed on nodules with

a needle or forceps under fluoroscopic guidance. A more recent development has

been the use of CT fluoroscopy for use in small nodules or those in a difficult

location [21]. Fig. 1 shows a peripheral 2-cm nodule in the right upper lobe and

old scarring of the left upper lobe in a patient with a long history of smoking and

increasing cough. A CT-guided transthoracic needle biopsy of the right upper

lobe nodule was negative, but a nuclear medicine study (described later)

suggested malignancy. Because this lesion was not near the pleura, a wedge

resection for diagnosis could have been difficult. Therefore, the patient may have

faced a lobectomy without preoperative diagnosis. CT fluoroscopy during

bronchoscopy was used to direct the transbronchial needle into the lesion. The

biopsy revealed NSCLC.

Using the flexible bronchoscope Wang et al [22] brought modern-day TBNA

to the forefront of pulmonary medicine. This procedure can be applied to

enlarged mediastinal and hilar lymph nodes as a sensitive approach to confirming

local metastasis or to peripheral nodules for diagnosis of a primary tumor [22,23].

Still, a negative TNBA cannot be taken as a diagnosis of a benign lymph node

and mediastinoscopy is often necessary. Endobronchial treatment modalities can

be applied through the flexible bronchoscope and are most commonly used for

palliation. Endobronchial laser resection, cryotherapy, photodynamic therapy,

brachytherapy, and electrocautery are used for treatment of obstructing tumors.


Bronchoscopic treatment of superficial tumors may be curative, but this is an

uncommon application, and further research is needed before this becomes the

standard approach.

As a rule, if a patient has a suspicious pulmonary nodule and evidence of

metastasis, a biopsy of the metastatic lesion should be attempted first. Thus, if a

patient presents with a right lower lobe mass and enlarged subcarinal lymph

Fig. 1. CT scans from a patient with a peripheral pulmonary nodule suspicious for lung cancer. (A) A

2-cm nodule is seen in the right upper lobe and chronic scarring is seen in the left upper lobe. (B)

Using CT fluoroscopy during bronchoscopy, the bronchoscope is seen within the trachea and the

biopsy needle is located within the nodule. Cytology revealed non-small-cell lung cancer.


nodes, the first biopsy procedure should be the TBNA of the subcarinal region. If

the biopsy reveals malignant cells, a diagnosis and at least one part of staging

have been obtained. If the physician only addresses the primary mass, a second

staging procedure is still required.

The development of radiolabeled (18)F-fluoro-2-deoxy-glucose positron emis-

sion tomography (PET) has altered the usual approach to the evaluation of

suspected malignant nodules and lung cancer staging. More on the use of PET in

staging is discussed later. Malignant tumors have elevated metabolic rates

because of ongoing cell division. The PET scan measures uptake of labeled

glucose as a marker of metabolic activity. PET scanning has been shown to have a

high sensitivity for lung cancer when applied to cases of a solitary pulmonary

nodule [24]. The high metabolic activity of most tumors produces a bright signal

corresponding to the nodule. The specificity of PET is not as high and many

benign inflammatory lesions have produced false-positive results [25]. Thus, a

positive result requires further evaluation with biopsy or resection. The negative

result does not imply the lesion can be ignored; in all but the most suspicious

cases these lesions could be followed by serial CT scans and resected if there is

growth. If the clinician’s suspicion is extremely strong that a cancer is present,

PET evaluation of the nodule is not necessary because a positive or negative

result will require further evaluation. The PET scan in that case may be used

solely as a staging tool. The resolution of PET scanning is in the range of 1 cm.

Therefore, very small nodules that are PET negative require close observation for

interval growth.

Staging of lung caner

NSCLC and SCLC are generally staged differently, although the TNM

system can be used for both. SCLC is generally thought of as a systemic

disease and only two classifications are used, limited and extensive stage based

on the ability to include all disease in a single radiation port. Most SCLC

presents as extensive-stage disease. The staging of NSCLC is more complicated

and is the focus of this discussion. The accurate staging of lung cancer is

necessary for many reasons. The stage determines treatment unless limited by

functional status or comorbidity. If the staging is inadequate the treatment may

be as well. A peripheral 2-cm NSCLC without lymphatic spread can be treated

effectively with surgical resection alone with an excellent chance for cure. The

same size tumor with paratracheal lymph node involvement has a much different

prognosis and treatment would likely include chemoradiation. The presence of

lymph node metastasis is key and the screening tools used to assess for its

presence once a diagnosis is made must be highly sensitive. Malignant pleural

effusions portend a grave prognosis; therefore, every effusion in patients with

lung cancer must be thoroughly evaluated before proceeding with aggressive

care. Accurate staging is also crucial to ensure uniformity in reporting and

treatment research.


There have been several staging systems for lung cancer used by clinicians

over the years and the newer versions have increased in complexity (Table 1).

The first widely used TNM classification was published in 1974 [26]. It focused

on several characteristics that were found to impact outcome in surgically treated

lung cancer including the following: tumor size, tumor invasion of vital

structures, pneumonic complications, and nodal and metastatic spread. The

TNM system was applied and three stages were described. This early classifica-

tion accurately highlighted the favorable outcome of the small tumors with no

nodal spread. The advanced stage III grouping included a broad rage of

presentations including tumors with local nonbulky mediastinal involvement

and tumors with diffuse metastasis. Stage II was limited to the relatively small

number of T2N1M0 cases alone. Modifications of this first system followed,

which were developed and used by separate treatment and research groups. As

various staging classifications were accepted and applied by professional organ-

izations the sharing and comparison of treatment outcome data became difficult.

Thus, collaborative international research was hindered. In 1986, Mountain [27]

published a new staging system, which served as the international standard to

help with this problem. This system delineated four stages: stages I through IIIA

included local and locoregional disease that could be amenable to resection and

stages IIIB and IV included advanced inoperable disease. This system was used

by national and international collaborative groups for treatment and research

Table 1

TNM staging systems

Category 1974 1986a 1997a

Primary tumor (T) T1 Tis Tis

T2 T1 T1

T3 T2 T2

T3 T3

T4 T4

Regional lymph nodes (N) N0 N0 N0

N1 N1 N1

N2 N2 N2

N3 N3

Distant metastasis (M) M0 M0 M0

M1 M1 M1

Stages I 0 0

II I IA

III II IB

IIIA IIA

IIIB IIB

IV IIIA

IIIB

IV

Data From: Mountain CF, Carr DT, Anderson WA. A system for the clinical staging of lung cancer.

American Journal of Roentgenology, Radium Therapy & Nuclear Medicine 1974;120:130–8.

Mountain CF. A new international staging system for lung cancer. Chest 1986;89:225S–33S.)a Invasive tumors only.


Table 2

TNM descriptors

Primary tumor (T)

TX Primary tumor cannot be assessed, or tumor proven by the presence of malignant

cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1 Tumor � 3 cm in greatest dimension, surrounded by lung or visceral pleura, without

bronchoscopic evidence of invasion more proximal than the lobar bronchusa (ie, not

in the main bronchus)

T2 Tumor with any of the following features of size or extent:

> 3 cm in greatest dimension

Involves main bronchus, � 2 cm distal to the carina

Invades the visceral pleura

Associated with atelectasis or obstructive pneumonitis that extends to the hilar region

but does not involve the entire lung

T3 Tumor of any size that directly invades any of the following: chest wall (including

superior sulcus tumors), diaphragm, mediastinal pleura, a parietal pericardium; or

tumor in the main bronchus < 2 cm distal to the carina but without involvement

of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung

T4 Tumor of any size that invades any of the following: mediastinum, heart, great

vessels, trachea, esophagus, vertebral body, or carina; or tumor with a malignant

pleural or pericardial effusion;b or with satellite tumor nodule(s) within the ipsilateral

primary-tumor lobe of the lung

Regional lymph nodes (N)

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and

intrapulmonary nodes involved by direct extension of the primary tumor

N2 Metastasis to ipsilateral mediastinal and/or subcarinal lymph nodes

N3 Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral

scalene, or supraclavicular lymph nodes

Distant metastasis (M)

MX Presence of distant metastasis cannot be assessed

M0 No distant metastasis

M1 Distant metastasis presentc

From Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997;111:

1710–7.a The uncommon superficial tumor of any size with its invasive component limited to the

bronchial wall, which may extend proximal to the main bronchus, is also classified T1.b Most pleural effusions associated with lung cancer are caused by tumor. However, there are a few

patients in whom multiple cytopathologic examinations of pleural fluid show no tumor. In these cases,

the fluid is nonbloody and is not an exudate. When these elements and clinical judgment dictate that the

effusion is not related to the tumor, the effusion should be excluded as a staging element and the patient’s

disease should be staged T1, T2, or T3. Pericardial effusion is classified according to the same rules.c Separate metastatic tumor nodules in the ipsilateral nonprimary-tumor lobes of the lung also are

classified M1.


purposes until a revised system was published in 1997 [28]. The revised

classification represents the currently applied system (Tables 2, 3) It expanded

the stages to further separate groups with varied outcomes and clarified the stage

of tumors with satellite nodules, which often indicate advanced disease.

The staging process begins with radiographic findings. The CT scan descrip-

tion of the primary tumor, T, is adequate for size and local invasion in most cases.

Occasionally, MRI may be useful to assess for invasion of vital structures that

would affect the staging and resectability of lesions; this is particularly true for

Pancoast tumors. Further T staging may require bronchoscopy to delineate the

extent and location of endobronchial involvement. Nodal staging also begins with

a CT scan, although the sensitivity and specificity of CT are not adequate for it to

be the only tool [29–31]. Enlarged lymph nodes cannot be assumed to be

malignant. Reactive lymph nodes occur especially if there is a postobstructive

pneumonia. Thus, all enlarged lymph nodes require biopsy proof of malignancy.

TBNA via flexible bronchoscopy, when positive, is adequate, however, when

negative surgical biopsy is required. Traditionally, if there was no proof of lymph

node spread by needle biopsy, mediastinoscopy was recommended in most cases

to accurately stage the mediastinum prior to surgery. The dramatic difference in

survival between N2 and N0 cases supports this approach [28]. PET scanning has

been reported to have very high sensitivity for mediastinal lymph node involve-

ment, and many centers have begun to eliminate mediastinoscopy in cases of

negative PET results [32,33]. The search for distant metastasis, M, begins with a

Table 3

Stage grouping of TNM subsetsa

Stage TNM Subset

0 Carcinoma in situ

IA T1N0M0

IB T2N0M0

IIA T1N1M0

IIB T2N1M0

T3N0M0

IIIA T3N1M0

T1N2M0

T2N2M0

T3N2M0

IIIB T4N0M0

T4N1M0

T4N2M0

T1N3M0

T2N3M0

T3N3M0

T4N3M0

IV Any T, any N M1

Data From Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest

1997;111: 1710–7.a Staging is not relevant for occult carcinoma, designated TXN0M0.


thorough history and physical and a routine CT of the chest. Common sites of

metastasis include the adrenal glands, liver, bone, and brain. The adrenals and

liver are routinely imaged on the chest CT scan. Specific brain and bone imaging

is indicated when a lesion is suspected but not generally recommended in all

cases. One advantage of PET scanning for staging is its ability to demonstrate

unsuspected and often asymptomatic metastases, which can prevent unnecessary

surgical intervention [34]. PET scanning may even provide prognostic data based

on intensity of uptake in a pulmonary tumor [35]. PET scanning is not able to

demonstrate brain lesions because of the high level of glucose metabolism at

baseline. Once the evaluation is complete a stage is assigned and this determines

treatment unless limited by medial status. All patients undergoing surgery should

complete the staging with hilar and mediastinal lymph node resection during the

operation. The final surgical stage is often different than the preoperative clinical

stage and more accurately reflects prognosis. In general, survival for patients with

tumors of any stage is higher for surgical staging because the clinical staging

includes some patients with unrecognized metastasis [28].

Treatment issues in elderly patients

A review of treatment strategies is beyond the scope of this article. This article

focuses on elderly patients with NSCLC and concerns about treatment toxicity.

Almost all lung cancer patients are candidates for treatment. The dilemmas present

only in the most advanced cases of metastatic disease in patients with significant

debilitation or critical illness. Given the relatively small survival benefit provided

by chemotherapy in stage IV disease and the significant toxicity in these types of

patients, it is prudent to use only palliative radiation or endobronchial therapywhen

needed or to limit interventions to end-of-life supportive care. In most cases,

however, appropriate therapy should at least be considered and discussed with the

patients and family. There is much literature supporting the use of standard

treatment in older patients; however there is also evidence that treatment may be

inappropriately withheld in this group as well [36,37].

Local disease is best treated with surgical resection of the tumor-bearing lobe,

which would include all stage I and II cases. Successful resection of all tumor

without evidence of mediastinal (N2) lymph node spread provides a reasonable

chance for cure and no further therapy is indicated. The preoperative assessment for

lung resection is often difficult. Almost all patients with lung cancer have a long

history of smoking and many have clinical COPD. Each patient must be evaluated

to ensure that the planned procedure does not result in severe respiratory

embarrassment. Few patients would want to undergo even curative resection if

faced with oxygen dependence and immobility for the remainder of their days.

Several risk factors for surgical morbidity and mortality have been docu-

mented. The most important is the extent of resection with pneumonectomy

consistently associated with a higher mortality rate than lobectomy [38–42].

Patients undergoing pneumonectomy are almost guaranteed a significant loss in


functional ability postoperatively. Often the tumor-bearing lobe is not contrib-

uting much to the overall ventilation and perfusion because of the malignant

invasion and removal may not impact on overall pulmonary or cardiovascular

status. Pneumonectomy is generally indicated when central tumor location makes

lobectomy with complete tumor resection impossible. There may be relatively

large amounts of normal perfused lung removed, however, leading to a rise in

pulmonary artery pressure and significant fall in forced expiratory volume in 1

second (FEV1) and forced vital capacity (FVC).

Preoperative lung function is related to surgical morbidity and is the primary

limiting factor for many patients [42–45]. The most commonly used measures of

lung function for preoperative evaluation are FEV1 and diffusing capacity for

carbon monoxide (DLCO). Both the preoperative value and the predicted post-

operative (PPO) values have been used in risk assessment [45]. The PPO values

are obtained using quantitative ventilation-perfusion scans, which delineate the

fraction of total lung function being performed by individual lobes. One can

calculate the PPO-FEV1 and DLCO using the baseline measures and subtracting

the percentage to be resected. This method has been shown to be relatively

accurate in predicting postsurgical lung function [46,47]. In lobectomy, in which

there may be a beneficial effect of removing some areas of emphysema (lung

volume reduction effect), the actual postoperative values are often higher than the

PPO assessments [46,48,49]. This is not the case in pneumonectomy, which again

highlights the need to approach that procedure with caution. The pulmonary

function test results and PPO calculations should focus on the percentage of

predicted values rather than absolute volume. For example, a very small elderly

woman tolerates a postoperative FEV1 of 0.8 L much better than a large man. In

general, PPO values less than 40% suggest high risk and consideration should be

made for alternative therapy [45]. The available alternatives may include a limited

operation such as wedge resection or segmentectomy or radiation alone [50,51].

In patients with borderline pulmonary function suggested by FEV1 or DLCO

of less than 60% of predicted values, further evaluation is almost always

indicated. The previously described quantitative ventilation-perfusion analysis

is helpful. A more recently applied global assessment is Cardiopulmonary

Exercise Testing (CPET) [52]. CPET involves a graded exercise test on a bicycle

ergometer with measurement of oxygen uptake (VO2) and work rate. This test is

useful for identifying pulmonary and cardiovascular limitations to exercise. The

peak VO2 has correlated well with surgical mortality in some studies. As with

pulmonary function test values, a PPO-VO2 can also be calculated. A peak VO2

of greater than 20 mL/kg/minute represents a low risk for surgery, 15 to 20 mL/

kg/minute a moderate risk, and less than 15 mL/kg/minute represents a high risk

[53]. A PPO-VO2 of less than 10 mL/kg/minute may be prohibitive [46].

Is age itself a risk factor for surgical morbidity and mortality? Some evidence

suggests that it is, most notably in the cases requiring pneumonectomy

[38,41,42,54]. The definition of ‘‘elderly’’ varies in these reports; some authors

report increased risk for patients older than 60 years and others report increased

risk for patients older than 70. With aging there is a loss of lung function as


measured by forced expiratory flow, which could lead to lower respiratory

reserve in the older age group [55]. However, this natural decrease in lung

elastic recoil does not lead to ventilatory limitation in healthy patients. The

pulmonary function abnormality in lung cancer patients is related to the cigarette

exposure more than the effects of age. The natural fall in FEV1 is taken into

account by using reference values for pulmonary function test interpretation and

highlights the importance of focusing on the percentage of predicted value rather

than the absolute number. Concern about the reported increase in risk of surgery

in elderly individuals may have led some surgeons to recommend more

conservative therapy in patients who were otherwise candidates for resection.

Others authors have not found age to be an independent risk factor and several

groups have published series of older patient outcomes to highlight the safety of

surgery in this group [36,40,56–58]. Certainly, age alone is never contraindicates

surgery if a patient chooses to pursue an aggressive course of treatment. For

patients requiring a lobectomy or lesser resection the same principles of

pulmonary function screening described previously and used for younger patients

should be used to assess the ability to tolerate the resection. It is only with

pneumonectomy that one may need to consider alternative treatments. A more

recent approach that shows promise for locally advanced NSCLC is preoperative

chemotherapy or combined chemoradiation [59]. These aggressive approaches do

increase morbidity and careful patient selection is important [60]. Patients

believed to be at increased risk should be evaluated by physicians who handle

large numbers of similar cases to offer the best chance for good outcome [41].

Radiation therapy is part of standard treatment for lung cancer. In localized but

medically unresectable NSCLC it is applied with curative intent [51]. In advanced

symptomatic disease, it is useful for palliation, both in the lung in the case of

bronchial obstruction or hemoptysis or at sites of metastasis, such as bone or brain.

In locally advanced stage III NSCLC and in limited stage SCLC radiation is

routinely used in combination with chemotherapy. In recent years there has been

success with initial chemoradiation followed by surgical resection in stage III

NSCLC, as noted previously [59]. Pulmonary toxicity from radiation therapy is

relatively common and includes radiation pneumonitis and fibrosis. These com-

plications are rarely severe or life threatening. More significant is the esophagitis

seen with mediastinal treatment in central tumors or stage III disease. This toxicity

is increased when chemotherapy is combined with radiation. Risk factors for

significant toxicity may include size of the radiation port, area of lung irradiated,

chemotherapeutic agent, poor pulmonary function, and possibly advanced age

[61–63]. Advanced age in itself does not contraindicate radiation therapy.

Chemotherapy is applied in combination with radiation therapy as described

for locally advanced disease. It is also the standard for stage IV disease where it

may improve survival and quality of life [64]. The toxicity of chemotherapy

varies with the wide array of agents available. Multiple agents have been shown

to have activity in SCLC and NSCLC and alternatives to first-line therapy should

be chosen to minimize toxicity in high-risk patients. The strongest risk factor for

chemotherapy-associated toxicity is performance status [65]. Debilitated patients


are not candidates for systemic treatment. Again, age alone dos not contraindicate

treatment with chemotherapy.

Summary

Lung cancer is one of the most common causes of death in elderly patients in the

United States. Treatment advances have improved survival in selected patients. The

available treatments carry the risk ofmorbidity andmortality but the benefit in most

patients far outweighs the risks, given the dismal prognosis of untreated disease.

Elderly patients with lung cancer need careful attention during pretreatment

assessment. Advanced age alone, however, should not contraindicate aggressive

treatment. In the high-risk groups it is important to involve a team of physicians

including surgeons, radiation oncologists, medical oncologists, and pulmonolo-

gists, who are familiar with current treatment options and their risks.

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Lung cancer in elderly patients

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