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.

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.

Gastric cancer is rampant in several countries around the world. Its incidence in the West has been on the decline for more than 40 years; however, the location of gastric cancer has shifted proximally in the past 15 years. The reason for this shift is not clear. Diffuse histology is also more common now than intestinal type of histology. Advances have been made in staging procedures such as laparoscopy and endoscopic ultrasonography and in possible functional imaging techniques. The current TNM classification requires an examination of at least 15 lymph nodes; therefore, at least a D1 dissection is recommended. Patients with locoregional gastric carcinoma should also be referred to high-volume treatment centers. Combination chemotherapy and radiotherapy in the adjuvant setting for select group of patients is considered the new standard in the United States. The NCCN Gastric Cancer Guidelines portray uniformity in the systemic approach to cancer in the United States. We look forward to the results of investigations of a number of new chemotherapeutic agents, including antireceptor agents, vaccines, gene therapy, and antiangiogenic agents. The panel anticipates many advances in the treatment of esophageal carcinoma in the future.

Esophageal cancer is a major health hazard in many parts of the world. The incidence of adenocarcinoma is rising in white men, particularly in the nonendemic areas, such as the West. Barrett's metaplasia, gastroesophageal reflux, hiatal hernia, and obesity are thought to play a role in these cases. In addition, the most common location of esophageal carcinoma has shifted to the lower third of the esophagus. Unfortunately, esophageal carcinoma is often diagnosed late; therefore, most therapeutic approaches are palliative. Advances have been made in staging procedures and in therapeutic approaches. The NCCN Esophageal Cancer Guidelines emphasize that palpable advances have been made in the treatment of locoregional esophageal carcinoma. Similarly, endoscopic palliation of esophageal carcinoma has improved substantially due to improving technology. A number of new chemotherapeutic agents are on the horizon including antireceptor agents, vaccines, gene therapy, and antiangiogenic agents. The panel expects numerous advances in the treatment of esophageal carcinoma in the future.

The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Cancer Centers, and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery.

To examine the role of adjuvant chemotherapy in the treatment of patients with deep muscle-invasive transitional cell carcinoma (TCC) of the bladder who have undergone cystectomy.