The majority of patients who acquire lung cancer will have troublesome symptoms at some time during the course of their disease. Some of the symptoms are common to many types of cancers, while others are more often encountered with lung cancer than other primary sites. The most common symptoms are pain, dyspnea, and cough. This document will address the management of these symptoms, and it will also address the palliation of specific problems that are commonly seen in lung cancer: metastases to the brain, spinal cord, and bones; hemoptysis; tracheoesophageal fistula; and obstruction of the superior vena cava.

The following two distinctly different issues should be taken into account when planning patient care following curative-intent therapy for lung cancer: adequate follow-up to manage complications related to the curative-intent therapy; and surveillance to detect recurrences of the primary lung cancer and/or development of a new primary lung cancer early enough to allow potentially curative retreatment. Follow-up for complications should be performed by the specialist responsible for the curative-intent therapy and should last 3 to 6 months. Recurrences of the original lung cancer will be more likely during the first 2 years after curative-intent therapy, but there will be an increased lifelong risk of approximately 1 to 2% per year of developing a metachronous, or new primary, lung cancer. A standard surveillance program for these patients is recommended based on periodic visits, with chest-imaging studies and counseling patients on symptom recognition. Whether subgroups of patients with a higher risk of developing a metachronous lung cancer (eg, those patients whose primary lung cancer was radiographically occult or central and those patients surviving for > 2 years after treatment for small cell lung cancer) should have a more intensive surveillance program is presently unclear. The surveillance program should be coordinated by a multidisciplinary tumor board and overseen by the physician who diagnosed and initiated therapy for the original lung cancer. Smoking cessation is recommended for all patients following curative-intent therapy for lung cancer.

Among patients with lung cancers, the proportion of those with small cell lung cancer (SCLC) has decreased over the last decade. SCLC is staged as limited-stage disease and extensive-stage disease. Standard staging procedures for SCLC include CT scans of the chest and abdomen, bone scan, and CT scan or MRI of the brain. The role for positron emission tomography scanning in the staging of SCLC has yet to be defined. Limited-stage disease is treated with curative intent with chemotherapy and radiation therapy, with approximately 20% of patients achieving a cure. The median survival time for patients with limited-stage disease is approximately 18 months. Extensive-stage disease is treated primarily with chemotherapy, with a high initial response rate of 60 to 70% and a complete response rate of 20 to 30%, but with a median survival time of approximately 9 months. Patients achieving a complete remission should be offered prophylactic cranial irradiation. Currently, there is no role for maintenance treatment or bone marrow transplantation in the treatment of patients with SCLC. Relapsed or refractory SCLC has a uniformly poor prognosis. In this section, evidence-based guidelines for the staging and treatment of SCLC are outlined.

This chapter of the Lung Cancer Guidelines addresses patients with particular forms of non-small cell lung cancer that require special considerations. This includes patients with Pancoast tumors, T4N0,1M0 tumors, satellite nodules in the same lobe, synchronous and metachronous multiple primary lung cancers (MPLC), and solitary metastases. For patients with a Pancoast tumor, a multimodality approach, involving chemoradiotherapy and surgical resection, appears optimal provided appropriate staging has been carried out. Patients with central T4 tumors that do not have mediastinal node involvement are uncommon. When carefully staged and selected, however, such patients appear to benefit from resection as part of the treatment as opposed to chemoradiotherapy alone. Patients with a satellite lesion in the same lobe as the primary tumor have a good prognosis and require no modification of the approach to evaluation and treatment from what would be dictated by the primary tumor alone. On the other hand, it is difficult to know how best to treat patients with a focus of the same type of cancer in a different lobe. Although MPLC do occur, the survival results after resection for either a synchronous presentation or a metachronous presentation with an interval of < 4 years between tumors are variable and generally poor, suggesting that many of these patients may have had a pulmonary metastasis rather than a second primary lung cancer. A thorough and careful evaluation of these patients is warranted to try to differentiate between patients with a metastasis and those with a second primary lung cancer, although criteria to distinguish them have not been defined. Finally, some patients with a solitary focus of metastatic disease in the brain or adrenal gland appear to benefit substantially from resection.

Stage IV non-small cell lung cancer (NSCLC) denotes the presence of metastatic disease and is largely incurable using present-day therapies. Chemotherapy remains a therapeutic option in this patient population, and there are many pertinent issues surrounding its use in patients with stage IV NSCLC. Eleven questions were framed by the American College of Chest Physicians Lung Cancer Guidelines Committee, and these were addressed by a systematic search of the available literature. The issues addressed included the identification of prognostic factors in selecting patients for chemotherapy and a critical analysis of the survival benefit provided by chemotherapy. Given the development of several new chemotherapy agents over the past decade, the impact that these agents have made was addressed as well as the definition of a standard of care regarding chemotherapeutic regimens. Given the fact that chemotherapy does not represent a curative option, other issues addressed were the optimal duration of treatment as well as its impact on symptom relief and quality of life, the role of second-line therapy, and the outcomes expectations from both first-line and second-line chemotherapy. The question of what specialty delivered the chemotherapy also was addressed. Once the data were identified, a critical analysis was undertaken attempting to objectively portray the data in support of answers for each of the questions posed. We believe the data support the fact that properly selected patients benefit from chemotherapy with regard to survival and palliation in both first-line and second-line settings. It appears that in trials addressing the duration of first-line therapy, this survival and palliative benefit occurs early, and prolonged therapy is not indicated. Therapy in this setting is cost-effective, and there are several regimens that can be considered to be "standard-of-care" options. Physicians involved in the diagnosis of these patients should be aware of the potential benefits of chemotherapy, allowing them to give recommendations to patients that are based on data derived from clinical trials. In addition, this awareness will allow them to make referrals, when appropriate, to physicians who are trained in the administration of chemotherapy and the management of patients undergoing such therapy.

Stage IIIB includes patients with T4, any N, M0, and any T, N3, M0. Surgery may be indicated only for carefully selected T4N0M0 patients with or without neoadjuvant chemotherapy or chemoradiotherapy. Patients with N3 lymph node involvement are not considered as surgical candidates. For patients with unresectable disease, good performance score, and minimal weight loss, treatment with combined chemotherapy and radiotherapy has resulted in better survival than treatment with radiotherapy alone. Multiple daily fractions of radiotherapy have not resulted in improved survival compared with standard fractionation once daily. Concurrent chemoradiotherapy appears to be associated with improved survival compared with sequential chemotherapy and radiotherapy. Treatment of stage IIIB due to malignant pleural effusion is addressed in the section that deals with stage IV disease.

Stage IIIA non-small cell lung cancer represents a relatively heterogeneous group of patients with metastatic disease to the ipsilateral mediastinal (N2) lymph nodes and also includes T3N1 patients. Presentations of disease range from apparently resectable tumors with occult microscopic nodal metastases to unresectable, bulky multistation nodal disease. Controversy abounds as to the optimal treatment of the various stage IIIA subsets, which is fueled by a lack of meaningful, large randomized trials. Multimodality therapy of some type appears to be preferable in stage IIIA patients.

Based on clinical assessment alone, patients with stage II non-small cell lung cancer (NSCLC) comprise only 5% of all patients with NSCLC. In addition, patients with stage II NSCLC represent a heterogeneous group, since stage II consists of patients with T1-2N1 or T3N0 tumors. By definition, patients with tumor invading the chest wall apex, mediastinum, diaphragm, or even the mainstem bronchus may all have T3 tumors. The extent of the data available regarding treatment of each of these different groups is therefore limited. The quality of the data is limited as well, because information often comes from small series of patients. Studies of adjuvant therapy after complete resection of stage II NSCLC are an important exception to this generalization, since data from large, randomized studies of adjuvant radiation therapy, chemotherapy, or a combination of the two are available for analysis. Superior sulcus tumors are discussed elsewhere in these guidelines.

The American Joint Committee on Cancer defines stage I non-small cell lung carcinoma (NSCLC) as consisting of patients with a T1 or T2 primary tumor designation and no evidence of hilar or mediastinal nodal disease (N0) or metastatic spread (M0). Medically fit patients in this clinical stage category based on conventional staging techniques should be considered for aggressive local therapy, and curative treatment is possible. Surgical resection is the accepted treatment for patients with this stage grouping, and full lobar or greater (lobectomy, pneumonectomy) rather than sublobar (wedge resection, segmentectomy) resection is strongly suggested. There is insufficient data to suggest that one method of resection (open thoracotomy, minimally invasive techniques) is superior to another. The performance of a systematic sampling or full mediastinal lymph node dissection may improve pathologic staging but is unproven therapeutically. There are no data supporting the routine use of chemotherapy in an adjuvant or neoadjuvant setting; however, recent phase II data suggest that neoadjuvant chemotherapy is feasible and safe, and larger phase III trials are now evaluating this modality. Primary radiation therapy should be considered for inoperable patients. The use of neoadjuvant or adjuvant radiation therapy in patients with stage I NSCLC is of unproven benefit.

Photodynamic therapy (PDT), brachytherapy, electrocautery, cryotherapy, and Nd-YAG laser therapy are therapeutic options available for management of endobronchial malignancies. All of these treatment modalities have been used for both palliation of late obstructing cancers, and more recently have been used as primary treatment of early radiographically occult cancers. We reviewed the evidence for the use of these treatment options in the management of early lung cancer.

A variety of invasive staging tests are available, including mediastinoscopy, thoracoscopy (video-assisted thoracoscopic surgery), transbronchial needle aspiration (TBNA), transthoracic needle aspiration (TTNA), and endoscopic ultrasound with fine needle aspiration (EUS-NA). Each of these tests requires specific skills, has particular risks, and has technical considerations making it more or less suitable for masses in particular locations. Therefore, direct comparisons among the tests are not possible, and the issue is to define which procedure is most useful for a particular situation. Invasive staging procedures are sometimes used to confirm the stage of a lung cancer, ie, when radiographic staging is not reliable. However, invasive staging procedures are also often used to confirm the diagnosis (ie, when the radiographic stage is reliable). The first situation requires a test with a low false-negative rate; the latter requires a test with high sensitivity. Clinicians must be clear about the question at hand and how to assess the value of a test when selecting an invasive staging procedure. When confirmation of the diagnosis is the primary issue, TBNA (or EUS-NA, if available) are good choices because of high sensitivity and low morbidity. When the primary issue is to confirm that there is no involvement of mediastinal lymph nodes, mediastinoscopy appears to be best suited to most situations. When the primary goal is to confirm malignant involvement of mediastinal nodes, mediastinoscopy also appears to be best in general, although TBNA, TTNA, and EUS-NA may be reasonable alternatives in certain situations. However, selection of a test will also depend on the local availability of expertise, and patient-specific anatomic and physiologic considerations. Selection of the optimal approach is best achieved through a multidisciplinary discussion so that all aspects can be weighed appropriately.

Correctly staging lung cancer is extremely important because the treatment options and the prognosis differ significantly by stage. Several noninvasive imaging studies are available to aid in identifying disease both within and outside of the chest. Chest CT scanning is useful in providing anatomic detail that better identifies the location of the tumor, its proximity to local structures, and whether or not lymph nodes in the mediastinum are enlarged. Unfortunately, the accuracy of chest CT scanning in differentiating benign from malignant lymph nodes in the mediastinum is unacceptably low. Whole-body positron emission tomography (PET) scanning provides functional information on tissue activity and has much better sensitivity and specificity than chest CT scanning for staging lung cancer in the mediastinum. In addition, metastatic disease can be detected by PET scan. Still, positive findings of PET scans can occur from nonmalignant etiologies (eg, infections), so that tissue sampling to confirm the suspected malignancy must be performed. The clinical evaluation tool, which is composed of a thorough history and physical examination, remains the best predictor of metastatic disease. If the findings from the clinical evaluation are negative, then imaging studies such as a CT scan of the head, a bone scan, or an abdominal CT scan are unnecessary, and the search for metastatic disease is complete. If signs, symptoms, or findings from the physical examination suggest the presence of malignancy, then sequential imaging, starting with the most appropriate study based on the clues obtained by the clinical evaluation, should be performed. Abnormalities detected by all of the aforementioned imaging studies are not always cancer. Unless overwhelming evidence of metastatic disease is present on an imaging study, in situations in which it will make a difference in treatment, all abnormal scan findings require tissue confirmation of malignancy so that patients are not precluded from having potentially curative surgery.

Lung cancer is usually suspected in individuals who have abnormal chest radiograph findings or have symptoms caused by either local or systemic effects of the tumor. The method of diagnosis of suspected lung cancer depends on the type of lung cancer (ie, small cell lung cancer or non-small cell lung cancer), the size and location of the primary tumor, the presence of metastasis, and the overall clinical status of the patient. Achieving a diagnosis and staging are usually done in concert because the most efficient way to make a diagnosis often is dictated by the stage of the cancer. The best sequence of studies and interventions in a particular patient involves careful judgment of the probable reliability of a number of presumptive diagnostic issues, so as to maximize the sensitivity and to avoid performing multiple or unnecessary invasive procedures. In this article, we consider all manner of clinical presentations of lung cancer in light of currently available diagnostic procedures. Published data supporting a particular diagnostic approach is weighed based on the quality of the benefit as well as the estimated net benefit. Recommendations are graded in terms of strength to provide clinicians with guidance as to the most efficient and approach to the diagnosis of lung cancer in individual patients.

The preoperative physiologic assessment of a patient being considered for surgical resection of lung cancer must consider the immediate perioperative risks from comorbid cardiopulmonary disease, the long-term risks of pulmonary disability, and the threat to survival due to inadequately treated lung cancer. As with any planned major operation, especially in a population predisposed to atherosclerotic cardiovascular disease by cigarette smoking, a cardiovascular evaluation is an important component in assessing perioperative risks. Measuring the FEV(1) and the diffusing capacity of the lung for carbon monoxide (DLCO) measurements should be viewed as complementary physiologic tests for assessing risk related to pulmonary function. If there is evidence of interstitial lung disease on radiographic studies or undue dyspnea on exertion, even though the FEV(1) may be adequate, a DLCO should be obtained. In patients with abnormalities in FEV(1) or DLCO identified preoperatively, it is essential to estimate the likely postresection pulmonary reserve. The amount of lung function lost in lung cancer resection can be estimated by using either a perfusion scan or the number of segments removed. A predicted postoperative FEV(1) or DLCO < 40% indicates an increased risk for perioperative complications, including death, from lung cancer resection. Exercise testing should be performed in these patients to further define the perioperative risks prior to surgery. Formal cardiopulmonary exercise testing is a sophisticated physiologic testing technique that includes recording the exercise ECG, heart rate response to exercise, minute ventilation, and oxygen uptake per minute, and allows calculation of maximal oxygen consumption (.VO(2)max). Risk for perioperative complications can generally be stratified by .VO(2)max. Patients with preoperative .VO(2)max > 20 mL/kg/min are not at increased risk of complications or death; .VO(2)max< 15 mL/kg/min indicates an increased risk of perioperative complications; and patients with .VO(2)max < 10 mL/kg/min have a very high risk for postoperative complications. Alternative types of exercise testing include stair climbing, the shuttle walk, and the 6-min walk. Although often not performed in a standardized manner, stair climbing can predict .VO(2)max. In general terms, patients who can climb five flights of stairs have O(2)max > 20 mL/kg/min. Conversely, patients who cannot climb one flight of stairs have .VO(2)max < 10 mL/kg/min. Data on the shuttle walk and 6-min walk are limited, but patients who cannot complete 25 shuttles on two occasions will have .VO(2)max < 10 mL/kg/min. Desaturation during an exercise test has been associated with an increased risk for perioperative complications. Lung volume reduction surgery (LVRS) for patients with severe emphysema is a controversial procedure. Some reports document substantial improvements in lung function, exercise capability, and quality of life in highly selected patients with emphysema following LVRS. Case series of patients referred for LVRS indicate that perhaps 3 to 6% of these patients may have coexisting lung cancer. Anecdotal experience from these case series suggest that patients with extremely poor lung function can tolerate combined LVRS and resection of the lung cancer with an acceptable mortality rate and good postoperative outcomes. Combining LVRS and lung cancer resection should probably be limited to those patients with heterogeneous emphysema, particularly emphysema limited to the lobe containing the tumor.

More than 150,00 patients a year present to their physicians with the diagnostic dilemma of a solitary pulmonary nodule (SPN) found either on chest radiography or chest CT. A thoughtful and timely workup of this finding is essential if lung cancer is to be recognized early and the chance for cure optimized. Based on the literature to date, recommendations are made for appropriate imaging modalities and diagnostic testing, as well as indications for obtaining preoperative tissue diagnosis for the patient with an SPN.

Although virtually all individuals with advanced lung cancer succumb to the disease, a substantial portion of individuals diagnosed at an earlier stage can be cured. This dichotomy has provoked interest in lung cancer screening. To date, randomized controlled trials of chest x-ray and sputum cytology have failed to demonstrate that screening with either modality decreases lung cancer mortality; neither of these technologies can be recommended. Early studies of lung cancer screening with low-dose CT (LDCT) appear promising; however, only data from observational studies are available. We recommend that individuals should only be screened with LDCT in the context of well-designed clinical trials.

Lung carcinogenesis is a chronic and multi-step process resulting in malignant lung tumors. This progression from normal to neoplastic pulmonary cells or tissues could be arrested or reversed through pharmacologic treatments, which are known as cancer chemoprevention. These therapeutic interventions should reduce or avoid the clinical consequences of lung cancer by treating early neoplastic lesions before the development of clinically evident signs or symptoms of malignancy. Preclinical, clinical, and epidemiologic findings relating to different classes of candidate chemopreventive agents provide strong support for lung cancer prevention as an attractive therapeutic strategy. Smoking prevention and smoking cessation represent an essential approach to reduce the societal impact of tobacco carcinogenesis. However, even if all the goals of the national antismoking efforts were met, there still would be a large population of former smokers who would be at increased risk for lung cancers. Lung cancer also can occur in those persons who never have smoked. This article focuses on what is now known about pharmacologic strategies for lung cancer prevention. Randomized clinical trials using beta-carotene, retinol, isotretinoin or N-acetyl-cysteine did not show benefit for primary and tertiary lung cancer prevention. There is also evidence that the use of beta-carotene and isotretinoin for lung cancer chemoprevention in high-risk individuals may increase the risk for lung cancer, especially in individuals who continue to smoke. There is a need for relevant in vitro models to identify pathways that activate chemopreventive effects in the lung. An improved understanding of cancer prevention mechanisms should aid in the design of clinical trials and in the validation of candidate chemopreventive targets as well as the discovery of new targets. Until such studies are completed, no agent or combination of agents should be used for lung cancer prevention outside of a clinical trial.