 |
Lung carcinoma
is the leading cause of cancer-related death worldwide. About 85%
of cases are related to cigarette smoking. Symptoms can include
cough, chest discomfort or pain, weight loss, and, less commonly,
hemoptysis; however, many patients present with metastatic disease
without any clinical symptoms. The diagnosis is typically made by
chest x-ray or CT scan and confirmed by biopsy. Depending on the
stage of the disease, treatment includes surgery, chemotherapy,
radiation therapy, or a combination. Despite advances in treatment, the
prognosis remains poor, with only 15% of patients surviving > 5
yr from time of diagnosis. For patients with stage IV (metastatic)
disease, the 5-yr overall survival rate is < 1%.
Improving survival requires focusing attention on smoking cessation,
early detection, and research into the genetic profile of lung tumors
and developing novel forms of therapy.
Epidemiology
In 2007, an estimated 213,380 new cases of lung cancer were diagnosed in the US, and about 160,390 people died from the disease. The incidence of lung cancer has been rising in women but appears to be leveling off in men.
Etiology
Cigarette smoking is the most important cause of lung cancer, accounting for about 85% of cases. The risk of cancer differs by age, smoking intensity, and smoking duration; the risk of cancer declines after smoking cessation, but it never returns to baseline. About 15% of people who develop lung cancer have never smoked. In these people, the exact reason lung cancer develops is unknown. Recent studies have reported that some never-smoking people with lung cancer have genetic mutations in the epidermal growth factor gene (EGFR). Although an environmental association has not clearly been established, it is theorized that exposure to radon gas, a breakdown product of naturally occurring radium and uranium, may be an environmental risk factor. Other possible risk factors include exposure to secondhand smoke and exposure to carcinogens, such as asbestos, radiation, arsenic, chromates, nickel, chloromethyl ethers, mustard gas, or coke-oven emissions, encountered or breathed in at work.
The risk of lung cancer increases with combined exposure to occupational carcinogens, toxins, and cigarette smoking. It is suspected that COPD and pulmonary fibrosis (α1-antitrypsin deficiency) may increase susceptibility to lung cancer. Also, active smokers who take β-carotene supplements have an increased risk of developing lung cancer. Air pollution and cigar smoke contain carcinogens; these substances have not been shown to cause lung cancer, although they may be associated with an increased risk. People whose lungs are scarred by other lung diseases (eg, TB) are at an increased risk of lung cancer.
Respiratory epithelial cells require prolonged exposure to cancer-promoting agents and accumulation of multiple genetic mutations before becoming neoplastic (an effect called field carcinogenesis). Over time, mutations in genes that stimulate cell growth (K-ras, MYC) cause abnormalities in growth factor receptor signaling (EGFR, HER2/neu), inhibit apoptosis (BCL-2), and contribute to proliferation of abnormal cells. In addition, mutations that inhibit tumor-suppressor genes (p53, APC) can lead to cancer.
Classification
Lung cancer is classified into 2 major categories:
SCLC is highly aggressive and almost always occurs in smokers. It is rapidly growing, and roughly 60% of patients have widespread metastatic disease at the time of diagnosis.
The clinical behavior of NSCLC is more variable and depends on histologic type, but about 40% of patients will have metastatic disease outside of the chest at the time of diagnosis.
Other features of the 2 categories (eg, location, risks, treatment, complications) also vary (see Table 3: Tumors of the Lungs: Features of Lung Cancer ).
|
Table 3
|
| | |
|
Features of Lung Cancer
|
|
Feature
|
Small Cell
|
|
Non–Small Cell
|
|
|
Adenocarcinoma
|
Squamous Cell
|
Large Cell
|
|
% of lung cancers
|
13–15%
|
25–35%
|
30–35%
|
10–15%
|
|
Location
|
Submucosa of airways, perihilar mass
|
Peripheral nodule or mass
|
Central, endobronchial
|
Peripheral nodule or mass
|
|
Risk factors
|
Smoking (essentially all patients)
|
Smoking (85% of patients; 15% never smoked); environmental and occupational exposures (asbestos, radiation, radon, secondhand smoke) are possible but not clearly established
|
|
Treatment
|
Etoposide or irinotecan or topotecan
carboplatin or cisplatin
Concurrent radiation therapy in limited-stage disease
No role for surgery
|
Stage I and II: Surgery with or without adjuvant chemotherapy
Stage IIIA: Surgery with or without adjuvant therapy or concurrent chemotherapy or radiation therapy; chemotherapy plus radiation therapy with surgery; chemotherapy with surgery; or chemotherapy plus radiation therapy
Stage IIIB: Radiation therapy with or without chemotherapy
Stage IV: Chemotherapy with or without palliative radiation therapy
|
|
Complications
|
Common cause of SVC syndrome, paraneoplastic syndromes
|
Hemoptysis, airway obstruction, pneumonia, pleuritic involvement with pain, pleural effusion, SVC syndrome, Pancoast's tumor (shoulder or arm pain), hoarseness (laryngeal nerve involvement), neurologic symptoms due to brain metastasis, pathologic fractures due to bone metastasis, jaundice due to liver metastasis
|
|
5-yr survival with treatment
|
Limited: 20%
Extensive: < 1%
|
Stage I: 57–67%
Stage II: 39–55%
Stage III: 5–25%
Stage IV: < 1%
|
|
SVC = superior vena cava.
|
|
Symptoms and Signs
About 25% of lung cancers are asymptomatic and are detected incidentally with chest imaging. Symptoms and signs can develop from local tumor progression, regional spread, or distant metastases. Paraneoplastic syndromes and constitutional symptoms may occur at any stage of the disease. Although symptoms are not specific to the classification or histology of the cancer, certain complications may be more likely with different types (see Table 3: Tumors of the Lungs: Features of Lung Cancer).
Local tumor:
The local tumor can cause cough and, less commonly, dyspnea due to airway obstruction, postobstructive atelectasis, and lymphangitic spread. Fever may occur with postobstructive pneumonia. Up to half of patients report vague or localized chest pain. Hemoptysis is less common, and blood loss is minimal, except in rare instances when the tumor erodes into a major artery, causing massive hemorrhage and death by exsanguination and asphyxiation.
Regional spread:
Regional spread of tumor may cause pleuritic chest pain or dyspnea from development of a pleural effusion, hoarseness due to tumor encroachment on the recurrent laryngeal nerve, and dyspnea and hypoxia from diaphragmatic paralysis due to involvement of the phrenic nerve.
Superior vena cava (SVC) syndrome results from compression or invasion of the SVC and can produce headache or a sensation of head fullness, facial or upper extremity swelling, supine breathlessness, and flushing (plethora). Physical signs of SVC syndrome include facial and upper extremity edema, dilated neck and subcutaneous veins over the face and upper trunk, and facial and truncal plethora.
Apical tumors, usually NSCLC, can invade the brachial plexus, pleura, or ribs, causing shoulder and upper extremity pain and weakness or atrophy of the ipsilateral hand (Pancoast's tumor). Horner's syndrome (ptosis, miosis, enophthalmos, and anhidrosis) results when the paravertebral sympathetic chain or cervical stellate ganglion is involved. Spread of tumor to the pericardium may be asymptomatic or lead to constrictive pericarditis or cardiac tamponade (see Pericarditis: Anatomy and Pathophysiology). Rarely, esophageal compression causes dysphagia.
Metastases:
Metastases eventually cause symptoms that vary by location. Metastases to the liver cause pain, GI symptoms, and ultimately hepatic insufficiency. Metastases to the brain cause behavioral changes, confusion, aphasia, seizures, paresis or paralysis, nausea and vomiting, and ultimately coma and death. Bone metastases can lead to severe pain and pathologic fractures. Although lung cancer commonly metastasizes to the adrenal glands, it rarely leads to adrenal insufficiency.
Paraneoplastic
syndromes:
Paraneoplastic syndromes are symptoms that occur at sites distant from a tumor or its metastases (see Overview of Cancer: Paraneoplastic Syndromes). Common paraneoplastic syndromes in patients with lung cancer include hypercalcemia (in patients with squamous cell carcinoma, which results because the tumor produces parathyroid hormone–related protein), syndrome of inappropriate antidiuretic hormone secretion (SIADH), finger clubbing with or without hypertrophic pulmonary osteoarthropathy, hypercoagulability with migratory superficial thrombophlebitis (Trousseau's syndrome), myasthenia (Eaton-Lambert syndrome), and various neurologic syndromes, including neuropathies, encephalopathies, encephalitides, myelopathies, and cerebellar disease. Mechanisms for neuromuscular syndromes involve tumor expression of autoantigens with production of autoantibodies, but the cause of most others is unknown.
Diagnosis
Chest x-ray is often the initial imaging test. It may show clearly defined abnormalities, such as a single mass or multifocal masses or a solitary pulmonary nodule (see Approach to the Patient With Pulmonary Symptoms: Solitary Pulmonary Nodule), an enlarged hilum, widened mediastinum, tracheobronchial narrowing, atelectasis, nonresolving parenchymal infiltrates, cavitary lesions, or unexplained pleural thickening or effusion. These findings are suggestive but not diagnostic of lung cancer and require follow-up with CT scans or combined PET–CT scans and cytopathologic confirmation.
CT demonstrates many characteristic anatomic patterns and appearances that may confirm the diagnosis. CT also can guide needle biopsy of accessible lesions and is useful for staging. If a lesion found on a plain x-ray is highly likely to be lung cancer, a PET–CT scan may be done. This study combines anatomic imaging from the CT scan with functional imaging from the PET scan. The PET images can help differentiate inflammatory and malignant processes.
The method used to obtain cells or tissue for confirmation depends on the accessibility of tissue and the location of lesions. Sputum or pleural fluid cytology is the least invasive method. In patients with productive cough, sputum specimens obtained on awakening may contain high concentrations of malignant cells, but yield for this method is < 50% overall. Pleural fluid is another convenient source of cells; a malignant effusion is a poor prognostic sign (see Table 4: Tumors of the Lungs: Proposed International Staging System for Lung Cancer*). In general, false-negative cytology readings can be minimized by obtaining as large a volume of sputum or fluid as possible early in the day and sending the sample to the pathology laboratory immediately to minimize delays in processing, which lead to cell breakdown.
A percutaneous biopsy is the next least invasive procedure. It is more useful for metastatic sites (supraclavicular or other peripheral lymph nodes, pleura, liver, adrenals) than for lung lesions because of the 20 to 25% risk of pneumothorax and also the risk of false-negative results.
Bronchoscopy is the procedure most often used for diagnosing lung cancer. In theory, the procedure of choice for obtaining tissue is the one that is least invasive. In practice, bronchoscopy is often done in addition to or instead of less invasive procedures, because diagnostic yields are greater and because bronchoscopy is important for staging. A combination of washings, brushings, biopsies, and fine-needle aspirations of visible endobronchial lesions and of paratracheal, subcarinal, mediastinal, and hilar lymph nodes often yields a tissue diagnosis.
Mediastinoscopy is the gold standard test for evaluating mediastinal lymph nodes but is a higher-risk procedure, which is usually used before surgery to confirm or exclude the presence of tumor in enlarged mediastinal lymph nodes.
Open lung biopsy, done via open thoracotomy or using video assistance (see Diagnostic and Therapeutic Pulmonary Procedures: Thoracoscopy and Video-Assisted Thoracoscopic Surgery), is indicated when less invasive methods do not provide a diagnosis in patients whose clinical characteristics and radiographic features strongly suggest that the tumor is resectable.
Screening:
No screening studies are universally accepted for healthy patients who do not have lung cancer. Clinical trials have evaluated screening chest x-rays in high-risk patients (smokers) to try to detect lung cancers at earlier stages, but mortality did not decline. Screening CT scans are being evaluated because they are more sensitive, but CT produces more false-positive readings, which increase the number of unnecessary invasive diagnostic procedures needed to verify the CT findings. Such procedures are costly and risk additional complications. A strategy of yearly CT screening of smokers with follow-up PET scan or high-resolution CT (HRCT) to evaluate indeterminate lesions is currently being studied. So far, this strategy does not seem to lessen mortality and cannot be recommended as routine practice. The future of screening may lie in a combination of molecular analysis for genetic markers (such as K-ras, p53, EGFR), sputum cytometry, and detection of cancer-related volatile organic compounds (eg, alkane, benzene) in exhaled breath.
Staging
For SCLC, there are two stages, limited and extensive. Limited-stage SCLC disease is cancer confined to one hemithorax (including ipsilateral lymph nodes) that can be encompassed within one tolerable radiation therapy port, unless there is a pleural or pericardial effusion. Extensive-stage disease is cancer outside a single hemithorax or the presence of malignant cells detected in pleural or pericardial effusions. Less than 1/3 of patients with SCLC will present with limited-stage disease; the remainder of patients often have extensive distant metastases.
For NSCLC, there are 4 stages, I through IV. Staging is based on tumor size, tumor and lymph node location, and the presence or absence of distant metastases (see Table 4: Tumors of the Lungs: Proposed International Staging System for Lung Cancer*).
Tests for initial evaluation and staging: All lung cancer patients need whole-body imaging. Different combinations of tests can be done. Some tests are done routinely, and others are done depending on whether the results would impact treatment decisions:
Measurement of serum Ca, alkaline phosphatase, liver function, immune system, kidney function, platelets, Hb, and electrolytes are needed to assist with treatment decisions.
If a PET–CT is not available, thin-section CT scanning from the neck to the upper abdomen (to detect cervical and supraclavicular and hepatic and adrenal metastases) is the one of the first staging tests for both SCLC and NSCLC. However, CT scans often cannot distinguish postinflammatory changes from malignant intrathoracic lymph node enlargement or benign lesions from malignant hepatic or adrenal lesions (distinctions that determine stage). Thus, other tests are usually done when abnormalities are present in these areas. PET scanning is a reasonably accurate, noninvasive test used to identify malignant mediastinal lymph nodes and other distant metastases (metabolic staging). Integrated PET–CT scanning, in which PET and CT images are combined into a single image by scanners in a single gantry, is more accurate for NSCLC staging than CT or PET alone or than visual correlation of the 2 tests. The use of PET and integrated PET–CT is limited by cost, availability, and specificity (ie, the test is quite sensitive and has an excellent negative predictive value, but its positive predictive value is not as high). When PET scan results are indeterminate, bronchoscopy, mediastinoscopy, or video-assisted thoracoscopic surgery (VATS) can be used to biopsy questionable mediastinal lymph nodes. Without PET scanning, hepatic or adrenal lesions must be evaluated by needle biopsy.
MRI of the chest is slightly more accurate than high-chest HRCT for staging apical tumors and cancers close to the diaphragm and provides an evaluation of the vasculature surrounding the tumors.
Blood tests are usually done. Ca and alkaline phosphatase levels, if elevated, suggest possible bony metastases. Other blood tests, such as CBC, serum albumin levels, AST, ALT, total bilirubin, electrolytes, and creatinine levels, have no role in staging but provide important prognostic information about the patient's ability to tolerate treatment and may demonstrate the presence of paraneoplastic syndromes.
All patients with suspected lung cancer should undergo brain imaging. Brain imaging is especially necessary in patients with headache or neurologic abnormalities. Patients with bone pain or elevated serum Ca or alkaline phosphatase levels should undergo a PET–CT or a radionuclide bone scan if PET–CT is not available.
|
Table 4
|
| | |
|
Proposed International
Staging System for Lung Cancer*
|
|
Category
|
Description
|
|
Primary tumor (T)
|
|
Tis
|
Carcinoma in situ
|
|
T1
|
Tumor ≤ 3 cm without invasion more proximal than the lobar bronchus
|
|
T1a
|
Tumor ≤ 2 cm
|
|
T1b
|
Tumor > 2 but ≤ 3 cm
|
|
T2
|
Tumor > 3 cm but ≤ 7 cm or with any of the following (any tumors with these features are T2a if ≤ 5 cm):
-
Involves the main bronchus ≥ 2 cm distal to carina
-
Invades the visceral pleura
-
Associated with atelectasis or obstructive pneumonia that extends to the hilar region but does not involve the whole lung
|
|
T2a
|
Tumor > 3 but ≤ 5 cm
|
|
T2b
|
Tumor > 5 but ≤ 7 cm
|
|
T3
|
Tumor > 7 cm or with any of the following:
-
Invades the chest wall, diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium, or main bronchus < 2 cm distal to carina but not the carina
-
Atelectasis or obstructive pneumonitis of the entire lung
-
Separate tumor nodules in the same lobe
|
|
T4
|
Tumor of any size with either of the following:
-
Invades the mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina
-
≥ 1 Satellite tumors in a different ipsilateral lobe
|
|
Regional lymph nodes (N)
|
|
N0
|
No regional lymph node metastasis
|
|
N1
|
Metastasis to ipsilateral peribronchial or ipsilateral hilar lymph node or both and to intrapulmonary nodes, including that by direct extension of the primary tumor
|
|
N2
|
Metastasis to ipsilateral mediastinal or subcarinal lymph node or both
|
|
N3
|
Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node or a combination
|
|
Distant metastasis (M)
|
|
M0
|
No distant metastasis
|
|
M1
|
Distant metastasis
|
|
M1a
|
Tumor with any of the following:
|
|
M1b
|
Distant metastasis
|
|
Stage 0:
|
Stage IIB: T2b N1 M0 or
T3 N0 M0
|
|
Stage IA: T1 N0 M0
|
Stage IIIA: T1–T3 N2 M0 or
T3 N1 M0 or
T4 N0–N1 M0
|
|
Stage IB: T2a N0 M0
|
Stage IIIB: T1–T4 N3 M0 or
T4 N2 M0
|
|
Stage IIA: T1–T2a N1 M0 or
T2b N0 M0
|
Stage IV: T (any) N (any) M1a–M1b
|
|
*This staging system has been proposed by the International Association for the Study of Lung Cancer and submitted to the American Joint Committee on Cancer for review. It may soon alter the staging system for lung cancer. The current staging system can be found in the AJCC Cancer Staging Manual 6th edition.
Adapted from Goldstraw P, Crowley J, Chansky K, et al: The IASLC Lung Cancer Staging Project: Proposals for the revision of the TMN stage groups in the forthcoming (seventh) edition of the TNM classification of malignant tumors. Journal of Thoracic Oncology 2(8):706, 2007.
|
|
Prognosis
The overall prognosis for lung cancer is poor. The median survival time for limited-stage SCLC is 20 mo, with a 5-yr survival rate of 20%. Patients with extensive-stage SCLC do especially poorly, with a 5-yr survival rate of < 1%.
The 5-yr survival rate of patients with NSCLC varies by stage, from 60 to 70% for patients with stage I disease to < 1% for patients with stage IV disease. On average, untreated patients with metastatic NSCLC survive 6 mo, whereas the median survival for treated patients is about 9 mo. Recently, patient survival has improved for patients with both early and later stage NSCLC. Evidence shows improved survival in early-stage disease when platinum-based chemotherapy regimens are used after surgical resection. In addition, targeted therapies have improved survival in patients with stage IV disease. However, given the disappointing results in patients with metastatic disease, efforts at reducing mortality have increasingly focused on early detection and active interventions to prevent disease. Basing therapy on molecular signatures within the tumors has been the focus of laboratory and translational research.
Treatment
Treatment varies by cell type and by stage of disease. Many patient factors not related to the tumor affect treatment choice. Poor cardiopulmonary reserve, undernutrition, frailty or poor physical performance status, comorbidities, including cytopenias, and psychiatric or cognitive illness all may lead to a decision for palliative over curative treatment or for no treatment at all, even though a cure with aggressive therapy might technically be possible.
Radiation therapy carries the risk of radiation pneumonitis when large areas of the lung are exposed to high doses of radiation over time. Radiation pneumonitis can occur up to 3 mo after treatment is completed. Cough, dyspnea, low-grade fever, or pleuritic chest pain may signal the condition, as may crackles or a pleural friction rub detected on chest auscultation. Chest x-ray may have nonspecific findings; CT may show a nonspecific infiltrate without an obvious mass. The diagnosis is often one of exclusion. Radiation pneumonitis can be treated with a corticosteroid taper over several weeks and bronchodilators for symptom relief.
Multiple chemotherapy regimens exist for treatment of lung cancer. In addition to standard chemotherapy drugs, several biologic agents that specifically target lung tumors are under investigation. EGFR tyrosine kinase inhibitors may be used in patients who have not responded to platinum-based or docetaxel therapy. Bevacizumab , a vascular endothelial growth factor inhibitor, is now used in combination with standard chemotherapy regimens in certain patients. Many other biologic agents are under investigation, including some that specifically target cancer cell signal transduction pathways or the angiogenesis pathways that supply O2 and nutrition to growing tumor cells.
Radiofrequency ablation, in which high-frequency electrical current is used to destroy tumor cells, is a newer technique that can sometimes be used in patients who have small, early-stage tumors or small tumors that have recurred in a previously irradiated chest. This procedure may preserve more lung function than open surgery does and, because it is less invasive, may be appropriate for patients who are not candidates for open surgery.
SCLC:
SCLC of any stage is typically initially responsive to treatment, but responses are usually short-lived. Chemotherapy, with or without radiation therapy, is given depending on the stage of disease. In many patients, chemotherapy prolongs survival and improves quality of life enough to warrant its use. Surgery generally plays no role in treatment of SCLC, although it may be curative in the rare patient who has a small focal tumor without spread (such as a solitary pulmonary nodule) who underwent surgical resection before the tumor was identified as SCLC.
Chemotherapy regimens of etoposide and a platinum compound (either cisplatin or carboplatin ) are commonly used, as are other drugs, such as irinotecan , topotecan , vinca alkaloids ( vinblastine , vincristine , vinorelbine ), alkylating agents ( cyclophosphamide , ifosfamide ), doxorubicin , taxanes ( docetaxel , paclitaxel ), and gemcitabine . In limited-stage disease, radiation therapy further improves response; the very definition of limited-stage disease as disease confined to a hemithorax is based on the significant improvement in survival observed with radiation. The use of cranial radiation to prevent brain metastases is also advocated in certain cases for both limited- and extensive-stage disease; micrometastases are common in SCLC, and chemotherapy has less ability to cross the blood-brain barrier.
In extensive-stage disease, treatment is based on chemotherapy rather than radiation therapy, although radiation therapy is often used as palliative treatment for metastases to bone or brain. In patients with an excellent response to chemotherapy, prophylactic brain irradiation is sometimes used as in limited-stage SCLC to prevent growth of SCLC in the brain. It is unclear whether replacing etoposide with topoisomerase inhibitors ( irinotecan or topotecan ) improves survival. These drugs alone or in combination with other drugs are also commonly used in refractory disease and in cancer of either stage that has recurred.
In general, recurrent SCLC carries a poor prognosis, although patients who maintain a good performance status should be offered a clinical trial.
NSCLC:
Treatment for NSCLC typically involves assessment of eligibility for surgery followed by choice of surgery, chemotherapy, radiation therapy, or a combination of modalities as appropriate, depending on tumor type and stage.
For stage I and II disease, the standard approach is surgical resection with either lobectomy or pneumonectomy combined with mediastinal lymph node sampling or complete lymph node dissection. Lesser resections, including segmentectomy and wedge resection, are considered for patients with poor pulmonary reserve. Surgery is curative in about 55 to 75% of patients with stage I and in 35 to 55% of patients with stage II disease.
Surgery is done only on NSCLC patients who will have adequate pulmonary reserve once a lobe or lung is resected. Patients with preoperative forced expiratory volume in 1 sec (FEV1) > 2 L generally tolerate pneumonectomy. Those with FEV1 < 2 L should undergo a quantitative xenon radionuclide perfusion scan to determine the proportion of function the patient can expect to lose from resection. Postoperative FEV1 can be predicted by multiplying percent perfusion of the nonresected lung by the preoperative FEV1. A predicted FEV1 > 800 mL or > 40% of the predicted normal FEV1 suggests adequate postoperative lung function, although studies of lung volume reduction surgery in COPD patients suggest that patients with FEV1 < 800 mL can tolerate resection if the cancer is located in poorly functional, bullous (generally apical) lung regions. Patients undergoing resection at hospitals that perform more resections have fewer complications and are more likely to survive than those who undergo surgery at hospitals that do fewer lung cancer procedures.
Adjuvant chemotherapy after surgery is now standard practice for patients with stage II or stage III disease, possibly also for patients with stage IB disease with tumors > 4 cm. Clinical trials have shown an increase in 5-yr survival rates with the use of adjuvant chemotherapy. However, the decision for adjuvant chemotherapy should depend on the patient's comorbidities and risk assessment. The role of neoadjuvant chemotherapy in early-stage NSCLC is under investigation.
Stage III disease is treated with either chemotherapy, radiation therapy, surgery, or a combination of therapies; the sequence and choice of treatment are dependent on the location of the patient's disease and comorbidities. In general, concurrent chemotherapy and radiation therapy are considered standard treatment for unresectable clinically staged IIIA disease, but the survival remains poor (median survival, 10 to 14 mo). Patients with stage IIIB disease with contralateral mediastinal nodal disease or supraclavicular nodal disease are offered either radiation therapy or chemotherapy or both. Patients with locally advanced tumors invading the heart, great vessels, mediastinum, or spine usually receive radiation therapy. In some patients (T4 N0 M0 tumors), surgical resection with either neoadjuvant or adjuvant combined chemotherapy and radiation therapy may be feasible. The 5-yr survival rate for patients with treated stage IIIB disease is 5%.
In stage IV disease, palliation of symptoms is the goal. Chemotherapy and radiation therapy may be used to reduce tumor burden, treat symptoms, and improve quality of life. However, median survival is only 9 mo, and < 25% of patients survive 1 yr. Surgical palliative procedures may be required and may include thoracentesis and pleurodesis of recurrent effusions, placement of indwelling pleural drainage catheters, bronchoscopic fulguration of tumors involving the trachea and mainstem bronchi, placement of stents to prevent airway occlusion, and, in some cases, spinal stabilization for impending spinal cord compression.
Recurrent disease:
Treatment options for disease that recurs after treatment vary by location and include repeat chemotherapy for local recurrence, radiation therapy for metastases, and brachytherapy for endobronchial disease when additional external radiation cannot be tolerated. Rarely, surgical resection of a solitary metastasis or for palliative purposes is considered. The treatment of a locally recurrent NSCLC follows the same guidelines as for primary tumor stages I to III. If surgery was used initially, radiation therapy is the main modality. If the recurrence manifests as distant metastases, patients are treated as stage IV with a focus on palliation.
Complications:
Asymptomatic malignant pleural effusions require no treatment. Initial treatment of a symptomatic effusion is with thoracentesis; symptomatic effusions that recur despite multiple thoracenteses are drained through a chest tube. Infusion of talc (or occasionally, tetracycline or bleomycin ) into the pleural space (a procedure called pleurodesis) scars the pleura, eliminates the pleural space, and is effective in > 90% of cases (see Mediastinal and Pleural Disorders: Pleural Effusion).
Treatment of SVC syndrome is the same as treatment of lung cancer, with chemotherapy (SCLC), radiation therapy (NSCLC), or both (NSCLC). Corticosteroids are commonly used but are of unproven benefit.
Treatment of Horner's syndrome caused by apical tumors is with surgery with or without preoperative radiation or with radiation therapy with or without adjuvant chemotherapy.
Treatment of paraneoplastic syndromes varies by syndrome (see Overview of Cancer: Paraneoplastic Syndromes).
End-of-life
care:
Because many patients with lung cancer die, the need for end-of-life care should be anticipated (see The Dying Patient). Symptoms of breathlessness can be treated with supplemental oxygen and bronchodilators. Pain, anxiety, nausea, and anorexia are especially common and can be treated with parenteral morphine ; oral, transdermal, or parenteral opioids; and antiemetics. The care provided by hospice programs is extremely well-accepted by patients and families, yet this intervention is markedly underused.
Prevention
No active interventions to prevent lung cancer are proven effective except for smoking cessation (see Smoking Cessation). Remediation of high radon levels in private residences removes known cancer-promoting radiation, but a reduction in lung cancer incidence is unproven. Increasing dietary intake of fruits and vegetables high in retinoids and β-carotene appears to have no effect on lung cancer incidence. Vitamin supplementation is either unproven (vitamin E) or harmful (β-carotene) in smokers. Preliminary evidence hinting that NSAIDs and vitamin E supplementation may protect former smokers from lung cancer requires confirmation. New molecular approaches targeting cell signaling and cell cycle pathways and tumor-associated antigens are under investigation.
Last full review/revision March 2008 by Waun Ki Hong, MD; Anne S. Tsao, MD
Content last modified March 2008
| |
