Overview of the initial evaluation, treatment and prognosis of lung cancer
Author
David E Midthun, MD Section Editor
James R Jett, MD Deputy Editor
Michael E Ross, MD
Last literature review version 18.2: May 2010 | This topic last updated: May 6, 2010 (More)
INTRODUCTION — Lung cancer is the most common cause of cancer mortality worldwide for both men and women, causing approximately 1.2 million deaths per year [1]. In the United States, in 2009, there will have been an estimated 219,000 new cases of lung cancer and 159,000 deaths [2]. In contrast, colorectal, breast, and prostate cancers combined will have been responsible for only 118,000 deaths.
Both the absolute and relative frequency of lung cancer have risen dramatically. As an example, the age-adjusted death rates from lung cancer were similar to that of pancreatic cancer prior to 1930 for men and prior to 1960 for women (figure 1 and figure 2) [2]. Around 1953, lung cancer became the most common cause of cancer deaths in men, and in 1985 it became the leading cause of cancer deaths in women. Although lung cancer deaths have begun to decline in men, the death rate in women continues to rise, and almost one-half of all lung cancer deaths now occur in women. (See "Women and lung cancer".)
The term lung cancer, or bronchogenic carcinoma, refers to malignancies that originate in the airways or pulmonary parenchyma. Approximately 95 percent of all lung cancers are classified as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). This distinction is required for staging, treatment, and prognosis. Other cell types comprise about 5 percent of malignancies arising in the lung.
This discussion will present an overview of diagnosis, treatment and prognosis of patients with NSCLC and SCLC. An overview of the risk factors, pathology, and clinical manifestations of lung cancer is presented separately. (See "Overview of the risk factors, pathology, and clinical manifestations of lung cancer".)
INITIAL EVALUATION — The three main issues to assess in a patient with a suspected lung cancer are the cell type (NSCLC versus SCLC), the stage of disease, and the functional status of the patient. These parameters are essential for appropriate patient management.
• Whether a lung cancer is a NSCLC or an SCLC is critical for treatment planning, and a tissue diagnosis is necessary.
• Staging for NSCLC is critical in determining the appropriate treatment for a patient with resectable disease and avoiding unnecessary surgery in advanced disease [3]. Staging of NSCLC utilizes the tumor, node, metastasis (TNM) system (table 1 and table 2 and table 3). (See "Diagnosis and staging of non-small cell lung cancer" and "Tumor node metastasis (TNM) staging system for non-small cell lung cancer".)
• Staging of SCLC uses the Veterans Administration Lung Study Group designations of limited (confined to one hemithorax) or extensive (beyond one hemithorax) disease [4]. This distinction is important since patients with limited disease may benefit from thoracic radiation therapy in addition to systemic chemotherapy. (See "Pathobiology and staging of small cell carcinoma of the lung".)
• Treatment of lung cancer, whether with surgery, chemotherapy, radiation therapy or a combination of these, can be associated with substantial toxicity. Patients with significant impairment due to their lung cancer or comorbid conditions may not be able to withstand resection or alternatively aggressive chemoradiotherapy. Performance status can be assessed by a variety of methods including the Karnofsky Performance Status (KPS) and the Eastern Cooperative Oncology Group Performance Scale (ECOG PS) (table 4 and table 5). The KPS was introduced in the 1940s and uses a 100-point scale and 11 measures to describe patient's abilities to pursue activities and perform work [5]. The ECOG PS uses a five-point scale and has been shown in a comparative study to be a better predictor of prognosis [6].
Diagnostic procedures and staging should be carried out simultaneously, even though it may be tempting to simply pursue a diagnosis when an obvious abnormality is present on imaging. As an example, in a patient with a 4 cm lung mass and mediastinal adenopathy on CT, a mediastinal node biopsy may provide a diagnosis and confirm N2 (IIIA) disease (figure 3A-B). In contrast, a transthoracic needle aspirate of the mass may provide a tissue diagnosis but does not stage the mediastinum. This can lead to the inappropriate assumption that mediastinal lymph nodes are involved or necessitate a second procedure. (See "Diagnosis and staging of non-small cell lung cancer" and "Tumor node metastasis (TNM) staging system for non-small cell lung cancer".)
NSCLC
Treatment — Surgical resection offers the best opportunity for long-term survival and cure in patients with resectable NSCLC. The appropriateness of surgical resection of candidates with known or suspected NSCLC includes preoperative staging and an assessment of performance status with concurrent comorbidities and pulmonary function to allow prediction of postoperative function.
A patient with lung cancer may be "resectable" by virtue of having a surgically removable NSCLC, but may not be "operable" due to poor pulmonary function or comorbidities. Advances in surgical technique, the role of limited resection, and postoperative care may provide the opportunity for surgical resection in patients who previously might not have been considered candidates for aggressive treatment. (See "Preoperative evaluation for lung resection".)
• Patients with stage I or II NSCLC should be treated with complete surgical resection whenever possible (figure 4). Postoperative adjuvant chemotherapy has been shown to improve survival in patients with pathologic stage II disease and may have a role for patients with stage IB NSCLC (table 1). (See "Management of stage I and stage II non-small cell lung cancer" and "Adjuvant systemic therapy in resectable non-small cell lung cancer".)
• Patients with stage I or II disease who are not candidates for surgical resection or who refuse surgery may be candidates for radiotherapy. Radiotherapy may be applied by conventional means, stereotactic radiosurgery, or radiofrequency ablation. Photodynamic therapy may also be useful as a primary treatment modality in carefully selected patients with superficial airway lesions (figure 4). (See "Management of stage I and stage II non-small cell lung cancer", section on 'Nonsurgical approaches' and "Photodynamic therapy of lung cancer".)
• For patients with pathologically proven stage III disease prior to definitive therapy, a combined modality approach using concurrent chemotherapy is generally preferred. The role of surgery following chemoradiotherapy is an area of active investigation. Surgery may also retain a role for carefully selected patients with T3 or T4 lesions and negative mediastinal lymph nodes. (See "Management of stage III non-small cell lung cancer".)
• In patients with clinical stage I or II disease, in whom tumor involvement of mediastinal lymph nodes (pathologic stage IIIA) is documented in the histologic evaluation of the surgical resection specimen, adjuvant chemotherapy has been shown to improve survival. (See "Adjuvant systemic therapy in resectable non-small cell lung cancer".)
• Patients with stage IV disease are generally treated with systemic therapy or a symptom-based palliative approach. In appropriately selected patients, chemotherapy and/or molecularly targeted therapy may prolong survival without sacrificing quality of life. Radiation therapy and surgery may also be useful for symptom palliation in some patients. (See "Overview of the treatment of advanced non-small cell lung cancer".)
• Patients with stage IV disease based upon the presence of an isolated metastasis (eg, brain, adrenal) may benefit from resection of the metastasis as well as aggressive treatment of the primary tumor [7]. (See "Treatment of brain metastases in favorable prognosis patients".)
• Local palliative measures may be useful in patients with uncontrolled pulmonary disease [8]. Dyspnea due to bulky central airway involvement may be palliated by rigid or flexible bronchoscopic removal of tumor using laser for coagulation or cryotherapy. Stenting may be necessary to maintain airway patency and allow external beam radiation. Brachytherapy can be applied locally by a bronchoscopy-directed catheter placement and may be helpful for recurrent or persistent disease in the airway. This approach is usually pursued after maximal external beam radiation. (See "Diagnosis and management of central airway obstruction".)
Prognosis of NSCLC
Stage of disease — The TNM stage at presentation in patients with NSCLC has the greatest impact on the prognosis.
The most extensive data relating stage to prognosis come from a validation series of over 31,000 cases from the Surveillance, Epidemiology and End Results (SEER) database used to validate the 7th TNM staging system (table 1) [9]. Survival decreased progressively with more advanced disease from a median of 59 months for patients with stage IA disease to four months for those with stage IV disease (figure 5). (See "Diagnosis and staging of non-small cell lung cancer" and "Tumor node metastasis (TNM) staging system for non-small cell lung cancer".)
Clinical parameters — Other clinical factors that exist at the time of diagnosis that can predict survival independent of the disease stage. Most of these factors were identified in studies that primarily included patients with advanced or inoperable NSCLC:
• Performance status — Poor performance status and weight loss have been associated with shortened survival [10-15]. Reduced appetite, a precursor of weight loss, also has negative prognostic implications [10].
• Ethnicity — African American ethnicity does not appear to be an independent predictor of poorer survival. Although some studies suggested that African Americans have a worse prognosis even after correcting for stage and treatment, a multivariate analysis indicated that performance status and weight loss account for these results [11].
Pathologic and molecular factors — Older studies of patients with NSCLC have given conflicting results as to whether the distinction between adenocarcinoma and squamous cell carcinoma affects prognosis [16-20]. Other pathologic factors that have been linked to prognosis in some studies include the degree of differentiation [21,22] and lymphatic invasion [23-26]. (See "Pathology of lung malignancies".)
Each histologic subtype can vary in its degree of differentiation. The impact of tumor differentiation on resectable NSCLC is uncertain. Some studies indicate that poorly differentiated tumors have a worse prognosis than better differentiated tumors [21,22]. However, this finding has not been universal [18].
Lymphatic vessel invasion has a negative impact on outcome [23-25]. In one study of 244 patients who had resected stage I NSCLC, five-year cancer-free survival was higher among patients without lymphatic vessel invasion (74 versus 54 percent) [24]. In contrast, the prognostic significance of blood vessel invasion is uncertain, with only some studies demonstrating a negative impact on outcome [21,22,24-26].
Occult lymph node metastasis (ie, micrometastasis) can be identified by using reverse transcriptase polymerase chain reaction (RT-PCR) to detect tumor markers in lymph nodes from patients with NSCLC [27]. However, such studies are limited by lack of laboratory standardization and reproducibility. The clinical significance of such findings will remain uncertain until long-term studies are reported.
No single molecular marker has been identified that consistently predicts outcome. However, early data from gene expression profiling is promising. (See "Adjuvant systemic therapy in resectable non-small cell lung cancer", section on 'Molecular markers' and "Overview of gene expression profiling and proteomics in clinical oncology".)
PET and PET-CT — Positron emission tomography (PET), alone or integrated with computed tomography (CT), is useful in the initial staging to identify sites of tumor involvement. Integrated PET-CT has been shown to improve staging over PET scanning alone [28]. (See "Role of imaging in the staging of non-small cell lung cancer", section on 'Positron emission tomography'.)
A tumor's metabolic activity can be measured using the standardized uptake value (SUV) to assess the tumor uptake of fluorodeoxyglucose. A meta-analysis, based upon 21 retrospective studies that included 2637 patients with stages I to IV NSCLC, found that a high SUV was associated with a poor prognosis [29]. A second meta-analysis, limited to patients with stage I NSCLC, also found that a lower FDG uptake was associated with a better prognosis [30]. PET (or PET-CT) may also be useful in predicting response to chemotherapy [31-33].
Additional studies are needed to establish the role of SUV as a prognostic tool or in predicting the response to treatment.
Recurrence after complete resection — Patients who undergo a complete resection for NSCLC may develop recurrent and/or metastatic disease. Multiple factors influence survival following disease recurrence.
In a series of 1073 patients who underwent a complete resection, recurrent NSCLC was identified in 445 patients (41 percent) [34]. The median time to recurrence following surgery was 11.5 months, and the median survival following recurrence was 8.1 months. Multivariate analysis identified several factors that predicted shorter survival following recurrence. These included poor performance status, disease-free interval of one year or less, prior use of neoadjuvant chemotherapy or adjuvant radiation therapy, and distant metastases (as opposed to intrathoracic recurrence alone).
SCLC
Treatment — SCLC is a disseminated disease in most patients, even at presentation. Thus systemic chemotherapy is an integral part of the initial treatment.
• Patients with limited stage disease are primarily treated with a combination of chemotherapy and radiation therapy, since the addition of radiation therapy has been shown to prolong survival compared to chemotherapy therapy alone. Surgery is not used except in the rare patient who presents with a solitary pulmonary nodule without metastases or regional lymph node involvement. (See "Thoracic radiotherapy in the treatment of limited stage small cell lung cancer" and "First-line chemotherapy for small cell lung cancer" and "Role of surgery in multimodality therapy for small cell lung cancer".)
• For patients with extensive stage SCLC, chemotherapy alone is used as the initial therapy. (See "First-line chemotherapy for small cell lung cancer".)
• Prophylactic radiation has been shown to decrease the incidence of brain metastases and prolong survival in patients with both limited and extensive stage SCLC who respond to their initial treatment. (See "Prophylactic cranial irradiation for patients with small cell lung cancer".)
Prognosis — The most important prognostic factor in patients with lung cancer is the stage of disease at presentation. The primary determinant of survival in patients with SCLC is the extent of disease at presentation. For patients with limited stage disease, median survivals range from 15 to 20 months, and the reported five-year survival rate is 10 to 13 percent. In contrast, for patients with extended stage disease, the median survival is 8 to 13 months, and the five-year survival rate is 1 to 2 percent. (See "First-line chemotherapy for small cell lung cancer", section on 'Benefit of therapy'.)
Clinical parameters also have prognostic importance in patients with SCLC [15]. Poor performance status and/or weight loss have been associated with shortened survival.
SIDE EFFECTS OF TREATMENT — Both curative and palliative treatment of lung cancer often involve multimodality approaches that may include surgery, radiation therapy, and systemic therapy with cytotoxic chemotherapy or molecularly targeted agents. (See 'SCLC' above.)
The side effects of systemic therapy are often of particular concern, because of their potential negative effects on quality of life both during and after treatment. The toxicities will vary depending upon the therapeutic regimen.
Common toxicities observed in patients being treated for lung cancer include the following:
• Chemotherapy-induced nausea and vomiting of variable severity may be seen with most chemotherapy regimens (table 6), but can usually be prevented or managed effectively with aggressive therapy. (See "Pathophysiology and prediction of chemotherapy-induced nausea and vomiting" and "Prevention and treatment of chemotherapy-induced nausea and vomiting".)
• Hematologic toxicity, including in particular anemia and neutropenia with an increased risk of infection, is seen with most cytotoxic chemotherapy regimens. (See "Hematologic consequences of malignancy: Anemia".)
• Nephrotoxicity, especially with chemotherapy regimens containing cisplatin, can be severe. Intensive hydration is required to prevent this complication. (See "Cisplatin nephrotoxicity".)
• Neurotoxicity, which is especially frequent with cisplatin and the taxanes (paclitaxel, docetaxel), is usually at least partially reversible after therapy is discontinued. (See "Neurologic complications of non-platinum cancer chemotherapy" and "Neurologic complications of platinum-based chemotherapy".)
• Cutaneous toxicity, manifested as an acneiform rash, is frequent with erlotinib and gefitinib. Although this side effect is troublesome, the presence of a rash is correlated with a response to therapy. (See "Cutaneous complications of molecularly targeted therapy and other biologic agents used for cancer therapy", section on 'EGFR signal transduction inhibitors' and "Small molecule epidermal growth factor receptor inhibitors for advanced non-small cell lung cancer".)
• Fatigue is frequent and may be due to systemic chemotherapy, radiation therapy, or the cancer itself. (See "Cancer-related fatigue: Prevalence, screening and clinical assessment".)
• Anorexia and weight loss are common in patients with lung cancer, and may be due to the disease or its treatment. (See "Clinical features and pathogenesis of cancer cachexia" and "Pharmacologic management of cancer anorexia/cachexia".)
INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. (See "Patient information: Lung cancer risks, symptoms, and diagnosis".) We encourage you to print or e-mail this topic, or to refer patients to our public web site www.uptodate.com/patients, which includes this and other topics.
SUMMARY — Lung cancer is the most common cause of cancer mortality worldwide for both men and women.
• The initial stage in management is to assess whether the patient has a NSCLC or a SCLC, the stage of the disease, and the overall performance status of the patient. (See 'Initial evaluation' above.)
• For patients with NSCLC, management is largely determined by the stage of disease. For patients with early stage disease, surgical resection offers the best opportunity for cure, while concurrent chemoradiotherapy is preferred for those with more extensive intrathoracic disease. In contrast, patients with advanced disease are managed palliatively with systemic therapy and/or local palliative modalities. (See 'NSCLC' above.)
• For patients with SCLC, systemic chemotherapy is an important component of treatment, because SCLC is disseminated at presentation in almost all patients. For those with limited stage disease, thoracic radiation therapy is used in combination with chemotherapy. Prophylactic cranial irradiation is often used to decrease the incidence of brain metastases and prolong survival. (See 'SCLC' above.)
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12. Stanley, KE. Prognostic factors for survival in patients with inoperable lung cancer. J Natl Cancer Inst 1980; 65:25.
13. Feinstein, AR. Symptomatic patterns, biologic behavior, and prognosis in cancer of the lung. Practical application of boolean algebra and clinical taxonomy. Ann Intern Med 1964; 61:27.
14. Kawaguchi, T, Takada, M, Kubo, A, et al. Performance status and smoking status are independent favorable prognostic factors for survival in non-small cell lung cancer: a comprehensive analysis of 26,957 patients with NSCLC. J Thorac Oncol 2010; 5:620.
15. Sculier, JP, Chansky, K, Crowley, JJ, et al. The impact of additional prognostic factors on survival and their relationship with the anatomical extent of disease expressed by the 6th Edition of the TNM Classification of Malignant Tumors and the proposals for the 7th Edition. J Thorac Oncol 2008; 3:457.
16. Gail, MH, Eagan, RT, Feld, R, et al. Prognostic factors in patients with resected stage I NSCLC: a report from the Lung Cancer Study Group. Cancer 1984; 54:1802.
17. Postoperative T1 N0 non-small cell lung cancer. Squamous versus nonsquamous recurrences. The Lung Cancer Study Group. J Thorac Cardiovasc Surg 1987; 94:349.
18. Harpole, DH Jr, Herndon JE, 2nd, Young, WG Jr, et al. Stage I nonsmall cell lung cancer. A multivariate analysis of treatment methods and patterns of recurrence. Cancer 1995; 76:787.
19. Pairolero, PC, Williams, DE, Bergstralh, EJ, et al. Postsurgical stage I bronchogenic carcinoma: morbid implications of recurrent disease. Ann Thorac Surg 1984; 38:331.
20. Martini, N, Bains, MS, Burt, ME, et al. Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg 1995; 109:120.
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Author
David E Midthun, MD Section Editor
James R Jett, MD Deputy Editor
Michael E Ross, MD
Last literature review version 18.2: May 2010 | This topic last updated: May 6, 2010 (More)
INTRODUCTION — Lung cancer is the most common cause of cancer mortality worldwide for both men and women, causing approximately 1.2 million deaths per year [1]. In the United States, in 2009, there will have been an estimated 219,000 new cases of lung cancer and 159,000 deaths [2]. In contrast, colorectal, breast, and prostate cancers combined will have been responsible for only 118,000 deaths.
Both the absolute and relative frequency of lung cancer have risen dramatically. As an example, the age-adjusted death rates from lung cancer were similar to that of pancreatic cancer prior to 1930 for men and prior to 1960 for women (figure 1 and figure 2) [2]. Around 1953, lung cancer became the most common cause of cancer deaths in men, and in 1985 it became the leading cause of cancer deaths in women. Although lung cancer deaths have begun to decline in men, the death rate in women continues to rise, and almost one-half of all lung cancer deaths now occur in women. (See "Women and lung cancer".)
The term lung cancer, or bronchogenic carcinoma, refers to malignancies that originate in the airways or pulmonary parenchyma. Approximately 95 percent of all lung cancers are classified as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). This distinction is required for staging, treatment, and prognosis. Other cell types comprise about 5 percent of malignancies arising in the lung.
This discussion will present an overview of diagnosis, treatment and prognosis of patients with NSCLC and SCLC. An overview of the risk factors, pathology, and clinical manifestations of lung cancer is presented separately. (See "Overview of the risk factors, pathology, and clinical manifestations of lung cancer".)
INITIAL EVALUATION — The three main issues to assess in a patient with a suspected lung cancer are the cell type (NSCLC versus SCLC), the stage of disease, and the functional status of the patient. These parameters are essential for appropriate patient management.
• Whether a lung cancer is a NSCLC or an SCLC is critical for treatment planning, and a tissue diagnosis is necessary.
• Staging for NSCLC is critical in determining the appropriate treatment for a patient with resectable disease and avoiding unnecessary surgery in advanced disease [3]. Staging of NSCLC utilizes the tumor, node, metastasis (TNM) system (table 1 and table 2 and table 3). (See "Diagnosis and staging of non-small cell lung cancer" and "Tumor node metastasis (TNM) staging system for non-small cell lung cancer".)
• Staging of SCLC uses the Veterans Administration Lung Study Group designations of limited (confined to one hemithorax) or extensive (beyond one hemithorax) disease [4]. This distinction is important since patients with limited disease may benefit from thoracic radiation therapy in addition to systemic chemotherapy. (See "Pathobiology and staging of small cell carcinoma of the lung".)
• Treatment of lung cancer, whether with surgery, chemotherapy, radiation therapy or a combination of these, can be associated with substantial toxicity. Patients with significant impairment due to their lung cancer or comorbid conditions may not be able to withstand resection or alternatively aggressive chemoradiotherapy. Performance status can be assessed by a variety of methods including the Karnofsky Performance Status (KPS) and the Eastern Cooperative Oncology Group Performance Scale (ECOG PS) (table 4 and table 5). The KPS was introduced in the 1940s and uses a 100-point scale and 11 measures to describe patient's abilities to pursue activities and perform work [5]. The ECOG PS uses a five-point scale and has been shown in a comparative study to be a better predictor of prognosis [6].
Diagnostic procedures and staging should be carried out simultaneously, even though it may be tempting to simply pursue a diagnosis when an obvious abnormality is present on imaging. As an example, in a patient with a 4 cm lung mass and mediastinal adenopathy on CT, a mediastinal node biopsy may provide a diagnosis and confirm N2 (IIIA) disease (figure 3A-B). In contrast, a transthoracic needle aspirate of the mass may provide a tissue diagnosis but does not stage the mediastinum. This can lead to the inappropriate assumption that mediastinal lymph nodes are involved or necessitate a second procedure. (See "Diagnosis and staging of non-small cell lung cancer" and "Tumor node metastasis (TNM) staging system for non-small cell lung cancer".)
NSCLC
Treatment — Surgical resection offers the best opportunity for long-term survival and cure in patients with resectable NSCLC. The appropriateness of surgical resection of candidates with known or suspected NSCLC includes preoperative staging and an assessment of performance status with concurrent comorbidities and pulmonary function to allow prediction of postoperative function.
A patient with lung cancer may be "resectable" by virtue of having a surgically removable NSCLC, but may not be "operable" due to poor pulmonary function or comorbidities. Advances in surgical technique, the role of limited resection, and postoperative care may provide the opportunity for surgical resection in patients who previously might not have been considered candidates for aggressive treatment. (See "Preoperative evaluation for lung resection".)
• Patients with stage I or II NSCLC should be treated with complete surgical resection whenever possible (figure 4). Postoperative adjuvant chemotherapy has been shown to improve survival in patients with pathologic stage II disease and may have a role for patients with stage IB NSCLC (table 1). (See "Management of stage I and stage II non-small cell lung cancer" and "Adjuvant systemic therapy in resectable non-small cell lung cancer".)
• Patients with stage I or II disease who are not candidates for surgical resection or who refuse surgery may be candidates for radiotherapy. Radiotherapy may be applied by conventional means, stereotactic radiosurgery, or radiofrequency ablation. Photodynamic therapy may also be useful as a primary treatment modality in carefully selected patients with superficial airway lesions (figure 4). (See "Management of stage I and stage II non-small cell lung cancer", section on 'Nonsurgical approaches' and "Photodynamic therapy of lung cancer".)
• For patients with pathologically proven stage III disease prior to definitive therapy, a combined modality approach using concurrent chemotherapy is generally preferred. The role of surgery following chemoradiotherapy is an area of active investigation. Surgery may also retain a role for carefully selected patients with T3 or T4 lesions and negative mediastinal lymph nodes. (See "Management of stage III non-small cell lung cancer".)
• In patients with clinical stage I or II disease, in whom tumor involvement of mediastinal lymph nodes (pathologic stage IIIA) is documented in the histologic evaluation of the surgical resection specimen, adjuvant chemotherapy has been shown to improve survival. (See "Adjuvant systemic therapy in resectable non-small cell lung cancer".)
• Patients with stage IV disease are generally treated with systemic therapy or a symptom-based palliative approach. In appropriately selected patients, chemotherapy and/or molecularly targeted therapy may prolong survival without sacrificing quality of life. Radiation therapy and surgery may also be useful for symptom palliation in some patients. (See "Overview of the treatment of advanced non-small cell lung cancer".)
• Patients with stage IV disease based upon the presence of an isolated metastasis (eg, brain, adrenal) may benefit from resection of the metastasis as well as aggressive treatment of the primary tumor [7]. (See "Treatment of brain metastases in favorable prognosis patients".)
• Local palliative measures may be useful in patients with uncontrolled pulmonary disease [8]. Dyspnea due to bulky central airway involvement may be palliated by rigid or flexible bronchoscopic removal of tumor using laser for coagulation or cryotherapy. Stenting may be necessary to maintain airway patency and allow external beam radiation. Brachytherapy can be applied locally by a bronchoscopy-directed catheter placement and may be helpful for recurrent or persistent disease in the airway. This approach is usually pursued after maximal external beam radiation. (See "Diagnosis and management of central airway obstruction".)
Prognosis of NSCLC
Stage of disease — The TNM stage at presentation in patients with NSCLC has the greatest impact on the prognosis.
The most extensive data relating stage to prognosis come from a validation series of over 31,000 cases from the Surveillance, Epidemiology and End Results (SEER) database used to validate the 7th TNM staging system (table 1) [9]. Survival decreased progressively with more advanced disease from a median of 59 months for patients with stage IA disease to four months for those with stage IV disease (figure 5). (See "Diagnosis and staging of non-small cell lung cancer" and "Tumor node metastasis (TNM) staging system for non-small cell lung cancer".)
Clinical parameters — Other clinical factors that exist at the time of diagnosis that can predict survival independent of the disease stage. Most of these factors were identified in studies that primarily included patients with advanced or inoperable NSCLC:
• Performance status — Poor performance status and weight loss have been associated with shortened survival [10-15]. Reduced appetite, a precursor of weight loss, also has negative prognostic implications [10].
• Ethnicity — African American ethnicity does not appear to be an independent predictor of poorer survival. Although some studies suggested that African Americans have a worse prognosis even after correcting for stage and treatment, a multivariate analysis indicated that performance status and weight loss account for these results [11].
Pathologic and molecular factors — Older studies of patients with NSCLC have given conflicting results as to whether the distinction between adenocarcinoma and squamous cell carcinoma affects prognosis [16-20]. Other pathologic factors that have been linked to prognosis in some studies include the degree of differentiation [21,22] and lymphatic invasion [23-26]. (See "Pathology of lung malignancies".)
Each histologic subtype can vary in its degree of differentiation. The impact of tumor differentiation on resectable NSCLC is uncertain. Some studies indicate that poorly differentiated tumors have a worse prognosis than better differentiated tumors [21,22]. However, this finding has not been universal [18].
Lymphatic vessel invasion has a negative impact on outcome [23-25]. In one study of 244 patients who had resected stage I NSCLC, five-year cancer-free survival was higher among patients without lymphatic vessel invasion (74 versus 54 percent) [24]. In contrast, the prognostic significance of blood vessel invasion is uncertain, with only some studies demonstrating a negative impact on outcome [21,22,24-26].
Occult lymph node metastasis (ie, micrometastasis) can be identified by using reverse transcriptase polymerase chain reaction (RT-PCR) to detect tumor markers in lymph nodes from patients with NSCLC [27]. However, such studies are limited by lack of laboratory standardization and reproducibility. The clinical significance of such findings will remain uncertain until long-term studies are reported.
No single molecular marker has been identified that consistently predicts outcome. However, early data from gene expression profiling is promising. (See "Adjuvant systemic therapy in resectable non-small cell lung cancer", section on 'Molecular markers' and "Overview of gene expression profiling and proteomics in clinical oncology".)
PET and PET-CT — Positron emission tomography (PET), alone or integrated with computed tomography (CT), is useful in the initial staging to identify sites of tumor involvement. Integrated PET-CT has been shown to improve staging over PET scanning alone [28]. (See "Role of imaging in the staging of non-small cell lung cancer", section on 'Positron emission tomography'.)
A tumor's metabolic activity can be measured using the standardized uptake value (SUV) to assess the tumor uptake of fluorodeoxyglucose. A meta-analysis, based upon 21 retrospective studies that included 2637 patients with stages I to IV NSCLC, found that a high SUV was associated with a poor prognosis [29]. A second meta-analysis, limited to patients with stage I NSCLC, also found that a lower FDG uptake was associated with a better prognosis [30]. PET (or PET-CT) may also be useful in predicting response to chemotherapy [31-33].
Additional studies are needed to establish the role of SUV as a prognostic tool or in predicting the response to treatment.
Recurrence after complete resection — Patients who undergo a complete resection for NSCLC may develop recurrent and/or metastatic disease. Multiple factors influence survival following disease recurrence.
In a series of 1073 patients who underwent a complete resection, recurrent NSCLC was identified in 445 patients (41 percent) [34]. The median time to recurrence following surgery was 11.5 months, and the median survival following recurrence was 8.1 months. Multivariate analysis identified several factors that predicted shorter survival following recurrence. These included poor performance status, disease-free interval of one year or less, prior use of neoadjuvant chemotherapy or adjuvant radiation therapy, and distant metastases (as opposed to intrathoracic recurrence alone).
SCLC
Treatment — SCLC is a disseminated disease in most patients, even at presentation. Thus systemic chemotherapy is an integral part of the initial treatment.
• Patients with limited stage disease are primarily treated with a combination of chemotherapy and radiation therapy, since the addition of radiation therapy has been shown to prolong survival compared to chemotherapy therapy alone. Surgery is not used except in the rare patient who presents with a solitary pulmonary nodule without metastases or regional lymph node involvement. (See "Thoracic radiotherapy in the treatment of limited stage small cell lung cancer" and "First-line chemotherapy for small cell lung cancer" and "Role of surgery in multimodality therapy for small cell lung cancer".)
• For patients with extensive stage SCLC, chemotherapy alone is used as the initial therapy. (See "First-line chemotherapy for small cell lung cancer".)
• Prophylactic radiation has been shown to decrease the incidence of brain metastases and prolong survival in patients with both limited and extensive stage SCLC who respond to their initial treatment. (See "Prophylactic cranial irradiation for patients with small cell lung cancer".)
Prognosis — The most important prognostic factor in patients with lung cancer is the stage of disease at presentation. The primary determinant of survival in patients with SCLC is the extent of disease at presentation. For patients with limited stage disease, median survivals range from 15 to 20 months, and the reported five-year survival rate is 10 to 13 percent. In contrast, for patients with extended stage disease, the median survival is 8 to 13 months, and the five-year survival rate is 1 to 2 percent. (See "First-line chemotherapy for small cell lung cancer", section on 'Benefit of therapy'.)
Clinical parameters also have prognostic importance in patients with SCLC [15]. Poor performance status and/or weight loss have been associated with shortened survival.
SIDE EFFECTS OF TREATMENT — Both curative and palliative treatment of lung cancer often involve multimodality approaches that may include surgery, radiation therapy, and systemic therapy with cytotoxic chemotherapy or molecularly targeted agents. (See 'SCLC' above.)
The side effects of systemic therapy are often of particular concern, because of their potential negative effects on quality of life both during and after treatment. The toxicities will vary depending upon the therapeutic regimen.
Common toxicities observed in patients being treated for lung cancer include the following:
• Chemotherapy-induced nausea and vomiting of variable severity may be seen with most chemotherapy regimens (table 6), but can usually be prevented or managed effectively with aggressive therapy. (See "Pathophysiology and prediction of chemotherapy-induced nausea and vomiting" and "Prevention and treatment of chemotherapy-induced nausea and vomiting".)
• Hematologic toxicity, including in particular anemia and neutropenia with an increased risk of infection, is seen with most cytotoxic chemotherapy regimens. (See "Hematologic consequences of malignancy: Anemia".)
• Nephrotoxicity, especially with chemotherapy regimens containing cisplatin, can be severe. Intensive hydration is required to prevent this complication. (See "Cisplatin nephrotoxicity".)
• Neurotoxicity, which is especially frequent with cisplatin and the taxanes (paclitaxel, docetaxel), is usually at least partially reversible after therapy is discontinued. (See "Neurologic complications of non-platinum cancer chemotherapy" and "Neurologic complications of platinum-based chemotherapy".)
• Cutaneous toxicity, manifested as an acneiform rash, is frequent with erlotinib and gefitinib. Although this side effect is troublesome, the presence of a rash is correlated with a response to therapy. (See "Cutaneous complications of molecularly targeted therapy and other biologic agents used for cancer therapy", section on 'EGFR signal transduction inhibitors' and "Small molecule epidermal growth factor receptor inhibitors for advanced non-small cell lung cancer".)
• Fatigue is frequent and may be due to systemic chemotherapy, radiation therapy, or the cancer itself. (See "Cancer-related fatigue: Prevalence, screening and clinical assessment".)
• Anorexia and weight loss are common in patients with lung cancer, and may be due to the disease or its treatment. (See "Clinical features and pathogenesis of cancer cachexia" and "Pharmacologic management of cancer anorexia/cachexia".)
INFORMATION FOR PATIENTS — Educational materials on this topic are available for patients. (See "Patient information: Lung cancer risks, symptoms, and diagnosis".) We encourage you to print or e-mail this topic, or to refer patients to our public web site www.uptodate.com/patients, which includes this and other topics.
SUMMARY — Lung cancer is the most common cause of cancer mortality worldwide for both men and women.
• The initial stage in management is to assess whether the patient has a NSCLC or a SCLC, the stage of the disease, and the overall performance status of the patient. (See 'Initial evaluation' above.)
• For patients with NSCLC, management is largely determined by the stage of disease. For patients with early stage disease, surgical resection offers the best opportunity for cure, while concurrent chemoradiotherapy is preferred for those with more extensive intrathoracic disease. In contrast, patients with advanced disease are managed palliatively with systemic therapy and/or local palliative modalities. (See 'NSCLC' above.)
• For patients with SCLC, systemic chemotherapy is an important component of treatment, because SCLC is disseminated at presentation in almost all patients. For those with limited stage disease, thoracic radiation therapy is used in combination with chemotherapy. Prophylactic cranial irradiation is often used to decrease the incidence of brain metastases and prolong survival. (See 'SCLC' above.)
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