ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Selection of modality for diagnosis and staging of patients with suspected non-small cell lung cancer

Selection of modality for diagnosis and staging of patients with suspected non-small cell lung cancer
Literature review current through: Jan 2024.
This topic last updated: Nov 01, 2022.

INTRODUCTION — Non-small cell lung cancer (NSCLC) accounts for approximately 85 percent of all lung cancers [1]. Tissue biopsy is necessary for the diagnosis and staging of NSCLC so that appropriate therapies can be administered in a timely fashion. (See "Personalized, genotype-directed therapy for advanced non-small cell lung cancer".)

This topic will discuss the general approach to selecting a modality to obtain tissue from a target biopsy site (primary tumor, lymph node, distant metastasis) in patients with suspected NSCLC. The approach to patients with a solitary pulmonary nodule, overview of the initial evaluation and imaging of NSCLC, procedures used for tissue biopsy of NSCLC, and the Tumor Node Metastasis staging system for NSCLC are discussed in detail separately. (See "Diagnostic evaluation of the incidental pulmonary nodule" and "Clinical manifestations of lung cancer" and "Overview of the initial treatment and prognosis of lung cancer" and "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer" and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer" and "Tumor, node, metastasis (TNM) staging system for lung cancer".)

BIOPSY GOALS — The acquisition of tissue from the primary lung lesion or suspected metastases (eg, lymph nodes or distant organs) should ideally provide enough material for a timely and accurate histopathologic diagnosis with molecular characterization. Computed tomographic (CT), positron emission tomographic (PET) scanning, and/or other imaging modalities (eg, magnetic resonance imaging [MRI]) guide the clinician in choosing the optimal site(s) for tissue sampling. The goals must be balanced with minimizing patient risk and accommodating patient preferences. The goals do not necessarily change for patients with significant comorbid disease or those with suspected advanced-stage disease. However, the risks and potential complications of biopsy in these patients may limit the preferred options. (See 'Assessing patient risk' below.)

Efficient diagnosis and procedures — The preferred initial site for tissue biopsy is one that could simultaneously establish the histopathologic diagnosis and disease stage. However, if the initial selected diagnostic procedure does not establish the diagnosis or stage, additional procedures are necessary. Exceptions to this general approach may occur in patients with multiple limiting comorbidities or those with unambiguous clinical and radiographic evidence of metastasis.

Typical examples of utilizing the same procedure to acquire tissue for simultaneous diagnosis and staging of suspected NSCLC (table 1 and table 2) [2,3] include the following:

Suspected T1a-cN0M0 (Stage I): For surgical candidates with a highly suspicious but solitary and small (eg, 15 to 30 mm) peripheral lung lesion with no evidence of mediastinal nodal or distant disease, we prefer surgical resection of the lung lesion and intraoperative mediastinal lymph node sampling. This approach is based upon the rationale that surgical resection in this population results in the highest rates of long-term survival since the likelihood of lymph node metastasis is low. If there is uncertainty about potential lymph node disease, pathology from lymph nodes sampled at the time of surgery would then dictate whether additional therapy is warranted (image 1 and image 2).

Suspected M1b or M1c (stage IV): When imaging identifies suspected isolated (M1b) or multiple (M1c) metastases (eg, bone, adrenal or liver mass[es]), biopsy of such lesions may reveal NSCLC. In this setting, the identification of M1b or M1c disease obviates the need for further invasive testing of the lung or mediastinum, and allows the patient to proceed rapidly to initial therapy (image 3).

Suspected N2/N3 involvement (stage III): When imaging identifies mediastinal N2 (ipsilateral) or N3 (contralateral) lymph node enlargement, biopsy targeted at the affected lymph node(s) confirms the presence of N2 or N3 disease, respectively. This distinction becomes important since some cases with N2 nodal involvement (eg, T1aN2M0) may be eligible for treatment with induction chemotherapy followed by surgery, while patients with N3 NSCLC are not typically operable (image 4 and image 5).

The approach to selecting a modality and procedures used to biopsy suspected NSCLC are discussed separately. (See 'Approach to the patient' below and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer" and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Sampling metastatic disease'.)

Adequate biopsy size — Tissue sampling should ensure the provision of adequate material for histopathology and for immunohistochemical and molecular characterization studies [4-8]. Although practices are highly variable, specialized pathology laboratories can utilize sample volumes as small as 1 mm3 for both tumor typing and molecular characterization [9,10]. Both low sample volume as well as sampling error are important limitations of low volume biopsies such as needle aspirates or pleural fluid cytology. These specimens may not be sufficient for immunohistochemical or genetic studies, in which case repeat biopsy procedures will be necessary.

Surgical excision of tumor or lymph node provides tissue samples with the largest volume. These include video-assisted thoracoscopic biopsy and cervical mediastinoscopy. Techniques involving needle aspiration of tissue or body fluids yield the smallest volumes. The yield from needle procedures can be sufficient if specialized clinical resources are also present. For example, several studies have shown that sufficient material can be obtained by endobronchial ultrasound guided–transbronchial needle aspiration (EBUS-TBNA) when combined with rapid onsite cytologic evaluation (ROSE), rigorous bronchoscopy training and established laboratory protocols for specimen processing [6,11-20]. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Limitations'.)

ASSESSING PATIENT RISK — Many patients who undergo evaluation for suspected NSCLC have comorbidities that influence life expectancy as well as procedural and surgical safety. In all cases, individual assessment should weigh the expected diagnostic yield of the procedure against the risks associated with that procedure, as well as the patient’s preferences.

General assessment – Current acute illness (eg. acute myocardial infarction, stroke, sepsis) may increase procedural and anesthetic risks and require special consideration to balance these risks with the need to obtain timely tissue diagnosis. Similarly, chronic comorbidities identified by history (eg, heart failure, chronic obstructive pulmonary disease [COPD]) or by computed tomography (eg, emphysema) may prompt consideration of additional tests (eg, pulmonary function testing, echocardiography or cardiopulmonary exercise testing). Performance status can be assessed clinically by the Karnofsky scale (table 3), and the Eastern Cooperative Oncology Group (ECOG) (table 4) Performance Scale [21-23]. (See "Survival estimates in advanced terminal cancer" and "Systemic chemotherapy for cancer in older adults", section on 'Comorbidity and functional status' and "Comprehensive geriatric assessment for patients with cancer".)

Assessment for surgery – Candidates for surgical resection or biopsy should undergo pulmonary function testing and consultation with a thoracic or cardiothoracic surgeon. Patients with borderline pulmonary function or worrisome cardiorespiratory symptoms should also undergo functional cardiopulmonary testing or a myocardial perfusion study. The indications and tests involved in the preoperative evaluation of patients with suspected lung cancer is discussed elsewhere. (See "Preoperative physiologic pulmonary evaluation for lung resection" and "Evaluation of perioperative pulmonary risk" and "Overview of the initial treatment and prognosis of lung cancer".)

Assessment for less invasive modalities – Less invasive modalities include bronchoscopy, endobronchial ultrasound-guided transbronchial needle aspiration [EBUS-TBNA], transthoracic needle aspiration [TTNA], and transesophageal endoscopic ultrasound (EUS). In general, these procedures are low risk for major complications, although few population-based studies of procedure-related complications have been performed [24]. Minimally invasive endoscopic and image-guided procedures are not completely without risk and individual assessment is necessary to evaluate the ability of the patient to tolerate sedation and the potential complications of the procedure. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Endoscopic and percutaneous procedures'.)

It is critical to assess the benefit to the patient of knowing the diagnosis and the risk he or she is willing to take to obtain one. This assessment should occur in the context of their underlying comorbid condition(s), as well as willingness to undertake treatment and their expected response to treatment. For example, an intraparenchymal pulmonary nodule may be surrounded by large emphysematous bullae or occur in a patient with advanced chronic lung disease. Even if the suspected tumor is localized and potentially curable, risks associated with either percutaneous biopsy or surgical wedge resection may be prohibitively high [24]. Thus, a patient who is risk averse to procedure-related complications or patient with poor life expectancy from COPD may opt for a low-risk modality or lower sensitivity procedure (eg, conventional bronchoscopy) or choose to avoid diagnosis completely. (See "Legal aspects in palliative and end-of-life care in the United States" and "Ethical issues in palliative care".)

APPROACH TO THE PATIENT

General principles — The general approach to the diagnosis and staging of patients with suspected NSCLC is discussed here with the basic assumption that the diagnosis and stage is unknown. The same approach can be used to stage NSCLC in patients in whom the diagnosis is known but the stage is unknown. This approach is in general agreement with the guidelines from the American College of Chest Physicians (ACCP), the National Comprehensive Cancer Network (NCCN), the European Society of Thoracic Surgeons (ESTS), International Association for the Study of Lung cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS), and European Society of Gastrointestinal Endoscopy [25-29].  

The following general principles apply:

Assess clinical stage first – The diagnostic approach below is based upon suspected stage based on exam and radiographic findings. (See 'Assessing radiographic stage' below.)

Modality selection for biopsy based upon radiographic staging (table 5 and table 6 and table 1) – Modality selection depends upon the assessed history, examination and imaging findings. In general, endoscopic and image-guided modalities (eg, EBUS-TBNA, CT-TTFNA) are preferred over surgical modalities (eg, mediastinoscopy) for the initial biopsy. However, for suspected advanced staged disease, it is critical that the biopsy provide both histopathologic and molecular characterization. More than one procedure will sometimes be necessary. The selection of a second biopsy procedure should favor modalities that are more likely to yield large volume samples. The procedures used to biopsy suspected NSCLC are discussed in detail separately. (See 'Low risk N2/N3 mediastinal disease (localized peripheral lung cancer)' below and 'Intermediate and high risk N2/N3 mediastinal disease' below and 'Suspected advanced disease' below.)

Individualize the approach to biopsy – Many institutions utilize a multi-disciplinary team approach and clinical protocols for the diagnostic work-up and staging of suspected NSCLC [30]. The goal of such protocols is the provision of evidence-based care for patients with suspected NSCLC that aligned with the expertise and availability of modalities at the institution. All suggested approaches, including the one proposed below, should be tailored to the individual patient according to risk, benefit, and patient preferences. (See 'Individualizing the approach' below and 'Role of multidisciplinary teams' below.)

Assessing radiographic stage — Prior to biopsy, every patient with suspected NSCLC should undergo chest computed tomography (CT) with imaging through the upper abdomen, liver, and adrenal glands [25,27,31-33]. In our view, positron emission tomography (PET) or integrated PET/CT should be used more selectively, primarily to exclude occult regional or distant metastasis in those who are considered to have operable tumors.

Chest CT provides the basis for initial assessment of the tumor node metastasis (TNM) stage of disease (table 6 and table 1). Working knowledge of the TNM staging system, the mediastinal lymph node map (figure 1), and therapeutic options for each stage of NSCLC, are necessary prior to making a decision regarding the best biopsy site. In particular, assessing risk of N2/N3 lymph nodal involvement (low, intermediate, or high) and the risk of advanced metastatic disease is important, since these factors play a major role in the selection of modality.

Initial imaging of patients with suspected NSCLC is discussed in detail separately. (See "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer", section on 'Suggested approaches to diagnostic evaluation and radiographic staging'.)

Low risk N2/N3 mediastinal disease (localized peripheral lung cancer) — The risk of N2 disease (ipsilateral mediastinal and/or subcarinal lymph nodes) and N3 disease (contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph node) is low in patients with suspicious but solitary, small (15 to 30 mm) peripheral tumors and no adenopathy on CT imaging. This would be in the absence of enlarged nodes by CT or normal sized nodes that are avid on PET imaging. These patients have suspected T1a(mi)N0M0, T1aN0M0, T1bN0M0, or T1cN0M0 (ie, stage IA1/IA2/IA3) disease (table 6 and table 1). In this population, we suggest surgical wedge resection for diagnosis followed by lobectomy as appropriate for treatment, with intraoperative mediastinal lymph node systematic sampling or dissection rather than preoperative invasive mediastinal staging. The risk of N2 disease (ipsilateral mediastinal and/or subcarinal lymph nodes) and N3 disease (contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph node) is low in this population. Management of patients with smaller pulmonary nodules (<15 mm) is discussed elsewhere. (See "Diagnostic evaluation of the incidental pulmonary nodule".)

Support for this approach comes from trials utilizing preoperative PET/CT imaging that report a low prevalence, (approximately 10 percent), of metastatic N2/N3 disease (figure 1) in patients with suspected T1a-cN0M0 NSCLC (table 6 and table 1) [34-41]. However, these data apply specifically to smaller (≤3 cm) peripheral tumors that are not centrally located, close to, or involving N1 nodes (ie, ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes). Centrally located tumors can obscure nodal involvement on imaging studies, thereby lowering the negative predictive value of the imaging study, and in addition, are at intermediate risk of N2/N3 nodal involvement [36] .

The caveat to this approach is that some patients with small peripheral tumors will prove to have occult N1 or N2 disease for which surgery is not indicated. While studies have attempted to identify populations with peripherally located T1a-cN0M0 disease that may benefit from further testing prior to surgery, such a population remains undefined. As an example, one study suggested that occult disease is more likely to be missed in women and in tumors that do not classically show PET avidity (eg, low grade adenocarcinoma) [34]. Preoperative sampling can be considered but is not mandatory in these setting. (See "Management of stage I and stage II non-small cell lung cancer".)

Intermediate and high risk N2/N3 mediastinal disease — N2 nodes are ipsilateral mediastinal and/or subcarinal lymph node(s). N3 nodes are contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph node(s) (figure 1). Although the approach varies widely, as a general rule, mediastinal staging is required for most cases of central tumors and those with radiographically enlarged or PET avid N2 or N3 nodes. Assessing intermediate versus high is based upon the assessment of lymph node features including number, size, 18-fluoro-2-deoxyglucose (FDG)-PET appearance, absence of benign fat or calcification pattern, as well as the T factor of the primary lesion, and is discussed below.

Intermediate risk N2 and N3 nodal involvement — Patients at intermediate risk for N2/N3 nodal disease include those with centrally located suspected stage IA (T1a-cN0M0 disease), suspected stage IB (T2aN0M0), and suspected stage II (T2bN0M0, T3N0M0, any T1N1M0, any T2N1M0) NSCLC (table 6 and table 1). Patients with small central tumors (≤3 cm), younger age, and/or adenocarcinoma histology are also considered intermediate risk [42]. In these populations, tissue biopsy is typically is performed in a single session with conventional bronchoscopy (for the primary tumor) and endobronchial ultrasound (for mediastinal sampling).

N1 disease (ipsilateral hilar, peribronchial, and intrapulmonary nodes) increases the likelihood of N2 and N3 involvement, such that patients with hilar node enlargement are intermediate risk for N2/3 NSCLC. This category includes patients with radiologically-identified N1 disease (T1N1 or T2N1 tumors). In patients with centrally located tumors, the risk of N1 involvement is high, either because the tumor is close to a N1 node, or is located in a N1 nodal region (eg, hilum). In this setting, suspicious activity in a N1 region is not easily distinguished by CT or PET scan. In support, the high false negative rate (up to 25 percent) of imaging in this setting, suggests that the risk of missing occult N2/3 disease is high [35-37,43,44]. For patients with T2 lesions, preoperative staging of the mediastinum is controversial. However, we prefer to perform preoperative mediastinal staging given the significant prevalence (10 to 15 percent) of occult N2 disease in this population [43].  

High risk N2 or N3 nodal involvement — Patients in this group include those with enlarged N2/3 lymph nodes (eg, >1 cm) and/or FDG-PET-avid mediastinal N2/3 lymph nodes (regardless of size) (image 4 and image 5). Patients with suspected T4 (>7 cm) and T3 (5 to 7 cm) tumors as well as those of any size with suspected chest wall, pericardial or phrenic nerve invasion are also considered high risk for N2 or N3 disease, even in the absence of radiographically identified lymph node lesions.    

Patients with suspected mediastinal N2 or N3 disease by CT or PET scan, are clearly high risk for pathologically proven N2/3 NSCLC. Initial biopsies should be targeted to the suspected lymph node regardless of which modality indicates suspicion. There are two exceptions to this rule:  

Patients with bulky disease infiltrating the mediastinum (ie, T4 disease) are generally not considered to be surgical candidates (image 6). Thus, in this setting, radiologic imaging is often considered acceptable for assessment of disease stage and the primary goal of biopsy is solely diagnostic. (See "Management of stage III non-small cell lung cancer" and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer".)

Patients with suspected N3 disease in a supraclavicular or scalene node (ipsilateral or contralateral) should undergo biopsy of the lymph node rather than the mediastinum. (See 'Suspected advanced disease' below.)

Modality choice - mediastinal sampling — The selection of a biopsy procedure for patients with suspected mediastinal disease is made in the context of the location of the primary tumor and suspected lymph nodes, available expertise, treatment options for the suspected stage, and patient safety and preferences. When choosing one modality over another, knowledge of the accessibility of the primary tumor and lymph nodes (figure 1) by the wide variety of minimally invasive and invasive procedures is critical. In general, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with or without transesophageal endoscopic ultrasound fine needle aspiration (EUS-FNA) are the preferred first-step procedures for sampling suspected nodal metastasis(es). Recognizing that not all cases of suspected NSCLC are suitable candidates for this approach, alternative modalities and modifications are suggested based upon procedure availability, institutional expertise, and patient-specific factors. (See 'Individualizing the approach' below.)

EBUS/EUS needle aspiration — EBUS-TBNA with or without EUS-FNA is the preferred first-step procedure for patients with large, centrally located tumors and for those with suspicious nodal involvement in the anterior and superior mediastinum (2R, 2L, 3p, 4R, 4L, 7, 10R, 10L, 11R, 11L) (figure 1). This preference is based upon the reported high sensitivity of bronchoscopy with EBUS-TBNA to stage and diagnose NSCLC in this setting and its ability to access more nodal stations than the traditional gold standard, cervical mediastinoscopy [45-51]. Multiple needle passes by an experienced operator and rapid on site cytologic evaluation (ROSE) are suggested to increase the diagnostic yield of EBUS-TBNA samples [6,11-17,52,53]. EBUS and the studies that describe its sensitivity for the diagnosis and staging of NSCLC are discussed separately. (See "Endobronchial ultrasound: Indications, contraindications, and complications" and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Endobronchial ultrasound' and "Endobronchial ultrasound: Technical aspects".)

Consideration can be given to the addition of EUS-FNA to provide additional access to the posterior and inferior mediastinal lymph nodal stations (3p, 7, 8, and 9) (figure 1). Support for the combined approach (EBUS-TBNA plus EUS-FNA) comes from small randomized trials that suggested the combined approach enhance the sensitivity of staging and may reduce the incidence of futile thoracotomies [54,55]. This study and the diagnostic sensitivity of the combined approach for mediastinal staging are discussed in detail separately. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Combined modalities for mediastinal lymph node staging'.)

When EBUS-TBNA (+/- EUS-FNA) is available, the following general guidelines can be applied:

When EBUS-TBNA (+/- EUS-FNA) confirms NSCLC in a suspected lymph node, the disease can be adequately clinically staged (cTNM) provided the clinician is confident that the lymph node with the highest suspected stage has been biopsied and that there is no distant disease suspected. Occult distant disease may be assessed with PET imaging and brain imaging. Thus, when positive and the clinician is confident that this is the highest stage, no further tissue sampling is necessary. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Diagnostic and staging accuracy'.)

When EBUS-TBNA (+/- EUS-FNA) is negative or inconclusive in patients with enlarged lymph nodes by CT criteria or FDG-glucose avid on PET imaging, nodal metastasis can be missed and staging inaccurate. Thus, in this setting further biopsy is indicated. When possible, we prefer to proceed with a more invasive surgical approach (usually mediastinoscopy) rather than performing repeat endoscopic sampling. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Diagnostic and staging accuracy' and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Limitations' and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Surgical staging procedures'.)

The investigating clinician should always weigh the accuracy of EBUS-TBNA in the context of its limitations (eg, inability to access inferior [8, 9] and para-aortic [5, 6] nodes and variable operator proficiency). The limitations of EBUS-TBNA and the importance of individualizing the approach are discussed separately. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Limitations' and 'Individualizing the approach' below.)

Alternative modalities — Alternative modalities should be sought when lymph nodes are not amenable to EBUS-TBNA (eg, para-aortic and subaortic lymph node [stations 5 and 6]) or when EBUS-TBNA is not available or has failed to obtain adequate material for a diagnosis (either from a primary tumor or a lymph node).

The safest modality that maximizes the ability to achieve a diagnosis should be chosen for a specific target lesion. The options available for sampling the primary lesion are the following:

Conventional bronchoscopy (with bronchoalveolar lavage, bronchial biopsy, transbronchial biopsy, transbronchial needle aspiration [bronchoscopic-TBNA]) is useful for biopsy of large central lesions and selected peripheral lesions. EBUS can be performed in the same procedural session, particularly when rapid onsite cytopathology review is NOT available or if there are concerns about the diagnostic quality of EBUS biopsies on ROSE review. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Conventional bronchoscopy'.)

Image-guided transthoracic needle aspiration (TTNA) may be useful for peripheral lesions. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Transthoracic needle biopsy'.)

Image-guided bronchoscopy techniques (eg, electromagnetic navigational bronchoscopy) may be useful for peripheral lesions. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Enhanced, image-guided bronchoscopic techniques' and "Image-guided bronchoscopy for biopsy of peripheral pulmonary lesions".)

Video-assisted thoracic surgery (VATS) can access most primary tumors but carries a higher risk of perioperative morbidity and mortality. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Video-assisted thoracic surgery and robotically assisted thoracic surgery'.)

When a biopsy of the primary tumor is the initial target and less invasive procedures are nondiagnostic or unavailable, an additional surgical nodal staging procedure may be needed:

Cervical mediastinoscopy, the historical gold standard for staging the mediastinum, is a sensitive staging procedure for nodal stations easily accessed by this approach (1, 2, 3, 4, anterior 7, 10) (figure 1). (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Staging accuracy'.)

VATS is useful when other procedures have failed to acquire adequate tissue to diagnose and stage suspected NSCLC. It is well-suited to evaluating the extent of invasion (chest wall, mediastinal) by the primary tumor (T). It is also useful for sampling ipsilateral mediastinal lymph nodes (4, 5, 6, 7, 8, 9, 10 to 14) (figure 1) (N) and for detecting pleural involvement (nodules or effusion [eg, M1a disease] (table 6 and table 1). It typically cannot sample nodes on the contralateral side. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Video-assisted thoracic surgery and robotically assisted thoracic surgery'.)

Anterior mediastinotomy (Chamberlain procedure) is often the only option when suspicious lymph nodes are identified in the para-aortic and subaortic lymph node stations (station 5 and 6). EUS-FNA can reach the aorto-pulmonary window but is not readily available in many institutions. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Anterior mediastinotomy (Chamberlain procedure)'.)

Extended mediastinal cervical mediastinoscopy (ECM), video-assisted mediastinal lymphadenectomy (VAMLA), and transcervical extended mediastinal lymphadenectomy (TEMLA) are staging procedures that are not widely available. Their use is best dictated by expertise at the practicing institution. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Extended cervical mediastinoscopy' and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Video-assisted mediastinal lymphadenectomy' and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Transcervical extended mediastinal lymphadenectomy'.)

Suspected advanced disease — When isolated or multiple metastases (M1a, M1b, M1c) (table 5 and table 6 and table 1), or when scalene or supraclavicular node involvement (N3) is suspected, directed biopsy of these sites is indicated for pathological confirmation. Many of the techniques used to sample distant metastases depend upon low volume biopsies and cytology for diagnosis. Thus, consideration should be given to obtaining enough material at the time of biopsy for diagnosis, immunohistochemistry, and mutational analysis. (See 'Adequate biopsy size' above.)

Biopsy of distant sites (eg, liver or bone) is crucial because a positive sample will confirm stage IV disease and direct the patient to systemic treatment. Comparatively, a negative biopsy of a suspected metastasis (eg, benign nodule in the contralateral lung or benign pleural pathology) can dramatically change the stage designation and confirm the suitability of potentially curative surgery. When radiographic evidence is overwhelming for multiple sites of metastases (M1c), choosing the safest or easiest approach for pathologic confirmation of suspected NSCLC is preferable. (See "Management of stage I and stage II non-small cell lung cancer" and "Overview of the initial treatment of advanced non-small cell lung cancer" and "Management of stage III non-small cell lung cancer".)

Suggested procedures to obtain tissue for extrathoracic sites are discussed in this section. Imaging and accuracy of sampling distant sites is discussed separately. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Sampling metastatic disease' and "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer", section on 'Clinical-directed imaging'.)

Pleural (T2, T3, M1a) — Two common clinical presentations of pleural disease are: metastases associated with pleural effusion or multiple pleural-based nodules and direct extension of the primary tumor to the pleura or chest wall. Direct extension of the primary tumor into the visceral or parietal pleura needs to be distinguished from metastatic NSCLC to the pleural space. Primary tumor that infiltrates visceral or parietal pleura is staged as a T2 or T3 lesion, respectively (table 6 and table 1). These lesions are potentially resectable. In contrast, metastatic NSCLC discovered as solid lesion(s) in the visceral or parietal pleura that is distinct and separate from the primary tumor or as malignant cells in an effusion represent M1a disease that is inoperable. Thus, when pleural metastases are suspected, it is essential to sample the pleural space by thoracentesis for pleural fluid cytology and/or pleural biopsy [25,26,56-59]. In general, the following applies:

For patients with effusions suspected to be due to NSCLC, thoracentesis is indicated. Thoracentesis is performed under ultrasound guidance with a goal of drawing at least 50 mL of pleural fluid. If cytology is negative for cancer, repeated sampling should be considered before proceeding to open surgical biopsy or pleuroscopy (ie, thoracoscopy). If thoracentesis is diagnostically indeterminate, a thoracoscopic biopsy is indicated. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Suspected pleural metastases'.)

For patients with solid pleural lesions or thickening, a thoracoscopic or image-guided biopsy is necessary to confirm suspected NSCLC. Compared to either of these modalities, closed pleural needle biopsy is rarely, if ever, performed for sampling suspected pleural involvement in NSCLC; expertise in this procedure has waned considerably. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Suspected pleural metastases'.)

Lung (T3, T4, M1a) — Selecting a diagnostic procedure for potential metastases in the ipsilateral (T3 or T4) or contralateral lung uses the same principles as tool selection for diagnosis of the primary lung cancer. The approach to solitary pulmonary lesions and procedures used to biopsy suspected NSCLC are discussed in detail elsewhere. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Management' and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Intrathoracic'.)

Pericardium (T3, M1a) — Direct extension of the tumor to the parietal pericardium constitutes a T3 lesion (table 6 and table 1). Visceral pericardial involvement, pericardial effusion or malignant pericardial nodules are M1a disease. Most cases of pericardial NSCLC and all cases of pericardial effusions due to NSCLC are considered unresectable. Sampling and treating suspected malignant disease of the pericardium is discussed separately. (See "Pericardial disease associated with cancer: Clinical presentation and diagnosis" and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Intrathoracic'.)

Liver, adrenal gland, brain, bone — Extrathoracic metastases of these organs indicate M1b disease, if isolated, or M1c disease, if multiple.

Liver – Liver lesions can be sampled by CT or ultrasound (US)-guided percutaneous fine needle aspiration/biopsy or by EUS-FNA [60]. The choice of modality will depend upon local expertise. (See "Approach to liver biopsy" and "Evaluation and management of the adrenal incidentaloma", section on 'Fine-needle aspiration biopsy'.)

Adrenal gland – Adrenal gland lesions with radiographic features suspicious for malignancy can be sampled by percutaneous fine needle aspiration/biopsy or less commonly, by EUS-FNA [61-63]. However, the choice of modality for adrenal gland biopsy will depend upon local expertise. (See "Approach to liver biopsy" and "Evaluation and management of the adrenal incidentaloma", section on 'Fine-needle aspiration biopsy' and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer", section on 'Extrathoracic'.)

Brain – Biopsy of the brain is sometimes performed when patients present with neurological symptoms or signs and a focal abnormality is identified on brain imaging before it is established that the patient has a primary NSCLC in the chest. Brain biopsies are considered high risk procedures and are performed in limited circumstances when a brain lesion is detected by imaging during the evaluation of a patient with NSCLC; thus, neurosurgical consultation should be obtained to help weigh the potential benefits and harms of brain biopsy in the individual patient.

Bone – Typically a core biopsy by CT guidance is performed when the suspected lesion can be safely approached with a percutaneous core needle. However, practices may vary by institution and practitioner. Bone biopsies are suboptimal for molecular diagnostic studies due to the need for decalcification. Biopsy of other metastatic sites is preferable if they are present. Techniques used to biopsy bone are discussed separately. (See "Bone tumors: Diagnosis and biopsy techniques", section on 'Biopsy techniques'.)

Supraclavicular or scalene lymph node (N3) — Needle aspiration or core needle biopsy of a scalene or supraclavicular lymph node (N3) is a generally, low-risk procedure that is frequently used to identify suspected NSCLC involvement of lymph nodes in these locations, and should be the first choice for sampling when these nodes are found to be enlarged and/or hypermetabolic. (See "Evaluation of peripheral lymphadenopathy in adults", section on 'Localized lymphadenopathy'.)

INDIVIDUALIZING THE APPROACH — Despite the increasing availability of guidelines and algorithms for the diagnosis of NSCLC, most experts agree that the approach should be individualized. Factors that influence what site to biopsy and what modality to use include tumor location and characteristics, patient comorbidities, and local expertise, as well as patient values and preferences. In addition, institution-specific factors such as availability of equipment, procedural proficiency and training of clinicians for minimally invasive and invasive interventions, and pathological protocols, can alter the choice of test for tissue sampling [13,16]. The sensitivity of each procedure is discussed separately. (See "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer".)

Role of multidisciplinary teams — There has been a shift in practice towards a collaborative approach, such that many cancer centers incorporate a multidisciplinary team (MDT) for the discussion of collective decisions focused on the diagnosis and treatment of patients with lung cancer [4-8,27,30,56,64]. Lung cancer MDTs involve combinations of the following sub-specialties: a pulmonologist, interventional pulmonologist, medical and radiation oncologists, thoracic surgeon, pathologist, radiologist, and specialist nurse. The ease of communication between specialists for discussions regarding selection of tests and treatments has fueled the growth of MDTs within hospitals and clinics. In addition, MDTs can participate in drafting institutional protocols to optimize the utilization of available services and standardize their approach to the evaluation and treatment of patients with suspected NSCLC. Guidelines from the American College of Chest Physicians (ACCP), European Society of Thoracic Surgeons (ESTS), and International Association for the Study of Lung cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) can be used as resources for each institution to develop their own approach to tissue biopsy for the diagnosis and staging of NSCLC [6,25,27,28].

TNM STAGING — The eighth edition tumor node metastasis (TNM) staging system (table 1 and table 2 and table 6) is in effect and is discussed separately. (See "Tumor, node, metastasis (TNM) staging system for lung cancer".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Non-small cell lung cancer (The Basics)")

Beyond the Basics topics (see "Patient education: Non-small cell lung cancer treatment; stage I to III cancer (Beyond the Basics)" and "Patient education: Non-small cell lung cancer treatment; stage IV cancer (Beyond the Basics)")

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and management of lung cancer".)

SUMMARY AND RECOMMENDATIONS

The appropriate management of patients with non-small cell lung cancer (NSCLC) requires pathologic confirmation of the disease and accurate staging to determine treatment and prognosis. The target for biopsy should be selected based upon an initial evaluation consisting of a detailed history, physical examination, routine laboratory studies and imaging with chest computed tomography (CT). The approach should be tailored to the individual patient according to risk, benefit, patient preferences, and available expertise. (See 'Introduction' above and 'Biopsy goals' above.)

For all patients with suspected NSCLC, biopsy of the lung, lymph node, or distant organ should aim to provide enough material for histopathologic, immunohistochemical, and molecular assessment. Clinicians should aim to diagnose and stage NSCLC with a single procedure or the minimal number of invasive procedures if more than one is required. (See 'Adequate biopsy size' above and 'Efficient diagnosis and procedures' above.)

All patients with suspected NSCLC should undergo CT of the chest (preferably contrast-enhanced) including the liver and adrenal glands prior to biopsy. In addition, whole body 18-fluoro-2 deoxyglucose (FDG) positron emission tomography (PET) or integrated PET/CT can be helpful in select populations such as those being considered for surgical resection. These imaging tests provide the basis for the initial assessment of the tumor node metastasis (TNM) stage (table 1 and table 2 and table 6) of disease and guide the clinician toward choosing the optimal biopsy site and biopsy method. (See 'Assessing radiographic stage' above.)

For most patients with highly suspicious or known NSCLC who are at low risk of N2 or N3 lymph nodal disease (ie, small [15 to 30 mm] peripheral tumors without suspected lymph node or distant spread), we suggest surgical resection with intraoperative mediastinal lymph node sampling or dissection rather than preoperative invasive staging of the mediastinum. (See 'Low risk N2/N3 mediastinal disease (localized peripheral lung cancer)' above.)

For most patients who are at intermediate risk or high risk of N2/N3 mediastinal lymph node involvement, preoperative, minimally invasive mediastinal lymph node sampling is typically indicated (see 'Intermediate and high risk N2/N3 mediastinal disease' above):

The modality for mediastinal tissue sampling is selected in the context of the location of the primary tumor and suspected lymph nodes, available expertise, and patient safety and preferences. In general, the following applies:

-Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with or without transesophageal endoscopic ultrasound fine needle aspiration (EUS-FNA) is the preferred approach for tissue biopsy for accessible nodes. When EBUS-TBNA (with or without EUS-FNA) confirms NSCLC and the specimen is adequate for molecular analysis, no further diagnostic or staging workup is necessary, provided the clinician is confident that this is the highest stage. When EBUS-TBNA (with or without EUS-FNA) is negative or inconclusive, mediastinoscopy or intraoperative mediastinal lymph node systematic sampling or dissection is indicated. (See 'EBUS/EUS needle aspiration' above.)

-In patients with suspected NSCLC who are not suitable candidates for EBUS-TBNA/EUS-FNA or in whom EBUS-TBNA/EUS-FNA is inconclusive, an alternative modality (usually mediastinoscopy) is selected based upon procedure availability, institutional expertise, and patient-specific factors. (See 'Alternative modalities' above.)

The exception for mediastinal sampling is patients with suspected NSCLC who have radiologic evidence on CT of bulky disease infiltrating the mediastinum; radiologic imaging is considered acceptable for the assessment of disease stage and the primary goal of biopsy is to confirm the diagnosis of NSCLC while minimizing the risk of procedure-related complications. (See 'High risk N2 or N3 nodal involvement' above.)

For patients with suspected NSCLC in whom isolated or multiple metastases (M1a, M1b, M1c) or in whom scalene or supraclavicular node involvement (N3) is suspected, invasive sampling of these sites, rather than sampling of the primary tumor, is indicated for pathological confirmation of advanced disease. When radiographic evidence is overwhelming for multiple sites of metastases, choosing the safest or easiest approach for pathologic confirmation of suspected NSCLC is preferred. (See 'Suspected advanced disease' above.)

For patients with suspected NSCLC and a pleural effusion, thoracentesis is indicated. Thoracentesis is performed preferably under ultrasound guidance with a goal of drawing at least 50 mL of pleural fluid. If cytology is negative or inconclusive, repeated sampling can be considered before proceeding to thoracoscopic biopsy. (See 'Pleural (T2, T3, M1a)' above.)

For patients with solid pleural lesions or thickening, a thoracoscopic or image-guided biopsy is necessary to confirm suspected NSCLC. Closed pleural needle biopsy has limited utility for sampling suspected pleural involvement in NSCLC.

For those with suspected metastases to the contralateral lung or extrathoracic organs, the suspected metastasis should be sampled to confirm diagnosis and stage rather than the primary tumor, with the exception of brain. (See 'Lung (T3, T4, M1a)' above and 'Pericardium (T3, M1a)' above and 'Liver, adrenal gland, brain, bone' above.)

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65:5.
  2. Goldstraw P, Chansky K, Crowley J, et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2016; 11:39.
  3. American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th ed, Amin MB, Edge SB, Greene FL, et al (Eds), Springer, Chicago 2017.
  4. Travis WD, Brambilla E, Van Schil P, et al. Paradigm shifts in lung cancer as defined in the new IASLC/ATS/ERS lung adenocarcinoma classification. Eur Respir J 2011; 38:239.
  5. Ellis PM, Blais N, Soulieres D, et al. A systematic review and Canadian consensus recommendations on the use of biomarkers in the treatment of non-small cell lung cancer. J Thorac Oncol 2011; 6:1379.
  6. Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011; 6:244.
  7. Travis WD, Brambilla E, Riely GJ. New pathologic classification of lung cancer: relevance for clinical practice and clinical trials. J Clin Oncol 2013; 31:992.
  8. Dietel M, Bubendorf L, Dingemans AM, et al. Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group. Thorax 2016; 71:177.
  9. Lim EH, Zhang SL, Li JL, et al. Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC). J Thorac Oncol 2009; 4:12.
  10. Quinn AM, Hickson N, Adaway M, et al. Diagnostic Mutation Profiling and Validation of Non-Small-Cell Lung Cancer Small Biopsy Samples using a High Throughput Platform. J Thorac Oncol 2015; 10:784.
  11. Nakajima T, Yasufuku K, Takahashi R, et al. Comparison of 21-gauge and 22-gauge aspiration needle during endobronchial ultrasound-guided transbronchial needle aspiration. Respirology 2011; 16:90.
  12. Loukeris K, Vazquez MF, Sica G, et al. Cytological cell blocks: Predictors of squamous cell carcinoma and adenocarcinoma subtypes. Diagn Cytopathol 2012; 40:380.
  13. Ost DE, Ernst A, Lei X, et al. Diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration: results of the AQuIRE Bronchoscopy Registry. Chest 2011; 140:1557.
  14. Oki M, Saka H, Kitagawa C, et al. Randomized Study of 21-gauge Versus 22-gauge Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Needles for Sampling Histology Specimens. J Bronchology Interv Pulmonol 2011; 18:306.
  15. Yarmus LB, Akulian J, Lechtzin N, et al. Comparison of 21-gauge and 22-gauge aspiration needle in endobronchial ultrasound-guided transbronchial needle aspiration: results of the American College of Chest Physicians Quality Improvement Registry, Education, and Evaluation Registry. Chest 2013; 143:1036.
  16. Bulman W, Saqi A, Powell CA. Acquisition and processing of endobronchial ultrasound-guided transbronchial needle aspiration specimens in the era of targeted lung cancer chemotherapy. Am J Respir Crit Care Med 2012; 185:606.
  17. Mondoni M, Carlucci P, Di Marco F, et al. Rapid on-site evaluation improves needle aspiration sensitivity in the diagnosis of central lung cancers: a randomized trial. Respiration 2013; 86:52.
  18. Navani N, Brown JM, Nankivell M, et al. Suitability of endobronchial ultrasound-guided transbronchial needle aspiration specimens for subtyping and genotyping of non-small cell lung cancer: a multicenter study of 774 patients. Am J Respir Crit Care Med 2012; 185:1316.
  19. Bonifazi M, Sediari M, Ferretti M, et al. The role of the pulmonologist in rapid on-site cytologic evaluation of transbronchial needle aspiration: a prospective study. Chest 2014; 145:60.
  20. Yarmus L, Akulian J, Gilbert C, et al. Optimizing endobronchial ultrasound for molecular analysis. How many passes are needed? Ann Am Thorac Soc 2013; 10:636.
  21. de Kock I, Mirhosseini M, Lau F, et al. Conversion of Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group Performance Status (ECOG) to Palliative Performance Scale (PPS), and the interchangeability of PPS and KPS in prognostic tools. J Palliat Care 2013; 29:163.
  22. Subramaniam S, Thorns A, Ridout M, et al. Accuracy of prognosis prediction by PPI in hospice inpatients with cancer: a multi-centre prospective study. BMJ Support Palliat Care 2015; 5:399.
  23. Morita T, Tsunoda J, Inoue S, Chihara S. The Palliative Prognostic Index: a scoring system for survival prediction of terminally ill cancer patients. Support Care Cancer 1999; 7:128.
  24. Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann Intern Med 2011; 155:137.
  25. Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for staging non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143:e211S.
  26. Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143:e142S.
  27. De Leyn P, Lardinois D, Van Schil P, et al. European trends in preoperative and intraoperative nodal staging: ESTS guidelines. J Thorac Oncol 2007; 2:357.
  28. Ost DE, Yeung SC, Tanoue LT, Gould MK. Clinical and organizational factors in the initial evaluation of patients with lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143:e121S.
  29. Vilmann P, Clementsen PF, Colella S, et al. Combined endobronchial and esophageal endosonography for the diagnosis and staging of lung cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline, in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS). Endoscopy 2015; 47:545.
  30. Gaga M, Powell CA, Schraufnagel DE, et al. An official American Thoracic Society/European Respiratory Society statement: the role of the pulmonologist in the diagnosis and management of lung cancer. Am J Respir Crit Care Med 2013; 188:503.
  31. De Wever W. Role of integrated PET/CT in the staging of non-small cell lung cancer. JBR-BTR 2009; 92:124.
  32. Fischer B, Lassen U, Mortensen J, et al. Preoperative staging of lung cancer with combined PET-CT. N Engl J Med 2009; 361:32.
  33. Maziak DE, Darling GE, Inculet RI, et al. Positron emission tomography in staging early lung cancer: a randomized trial. Ann Intern Med 2009; 151:221.
  34. Gómez-Caro A, Garcia S, Reguart N, et al. Incidence of occult mediastinal node involvement in cN0 non-small-cell lung cancer patients after negative uptake of positron emission tomography/computer tomography scan. Eur J Cardiothorac Surg 2010; 37:1168.
  35. Pozo-Rodríguez F, Martín de Nicolás JL, Sánchez-Nistal MA, et al. Accuracy of helical computed tomography and [18F] fluorodeoxyglucose positron emission tomography for identifying lymph node mediastinal metastases in potentially resectable non-small-cell lung cancer. J Clin Oncol 2005; 23:8348.
  36. Verhagen AF, Bootsma GP, Tjan-Heijnen VC, et al. FDG-PET in staging lung cancer: how does it change the algorithm? Lung Cancer 2004; 44:175.
  37. Freixinet Gilart J, García PG, de Castro FR, et al. Extended cervical mediastinoscopy in the staging of bronchogenic carcinoma. Ann Thorac Surg 2000; 70:1641.
  38. Schmidt-Hansen M, Baldwin DR, Hasler E, et al. PET-CT for assessing mediastinal lymph node involvement in patients with suspected resectable non-small cell lung cancer. Cochrane Database Syst Rev 2014; :CD009519.
  39. Gómez-Caro A, Boada M, Cabañas M, et al. False-negative rate after positron emission tomography/computer tomography scan for mediastinal staging in cI stage non-small-cell lung cancer. Eur J Cardiothorac Surg 2012; 42:93.
  40. Billé A, Pelosi E, Skanjeti A, et al. Preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer: accuracy of integrated positron emission tomography and computed tomography. Eur J Cardiothorac Surg 2009; 36:440.
  41. Bousema JE, Dijkgraaf MGW, van der Heijden EHFM, et al. Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer: A Randomized Clinical Trial. J Clin Oncol 2023; 41:3805.
  42. O'Connell OJ, Almeida FA, Simoff MJ, et al. A Prediction Model to Help with the Assessment of Adenopathy in Lung Cancer (HAL). Am J Respir Crit Care Med 2016.
  43. Cerfolio RJ, Bryant AS, Ojha B, Eloubeidi M. Improving the inaccuracies of clinical staging of patients with NSCLC: a prospective trial. Ann Thorac Surg 2005; 80:1207.
  44. El-Osta H, Jani P, Mansour A, et al. Endobronchial Ultrasound for Nodal Staging of Patients with Non-Small-Cell Lung Cancer with Radiologically Normal Mediastinum. A Meta-Analysis. Ann Am Thorac Soc 2018; 15:864.
  45. Ernst A, Anantham D, Eberhardt R, et al. Diagnosis of mediastinal adenopathy-real-time endobronchial ultrasound guided needle aspiration versus mediastinoscopy. J Thorac Oncol 2008; 3:577.
  46. Herth F, Becker HD, Ernst A. Conventional vs endobronchial ultrasound-guided transbronchial needle aspiration: a randomized trial. Chest 2004; 125:322.
  47. Yasufuku K, Chiyo M, Koh E, et al. Endobronchial ultrasound guided transbronchial needle aspiration for staging of lung cancer. Lung Cancer 2005; 50:347.
  48. Herth FJ, Eberhardt R, Vilmann P, et al. Real-time endobronchial ultrasound guided transbronchial needle aspiration for sampling mediastinal lymph nodes. Thorax 2006; 61:795.
  49. Vincent BD, El-Bayoumi E, Hoffman B, et al. Real-time endobronchial ultrasound-guided transbronchial lymph node aspiration. Ann Thorac Surg 2008; 85:224.
  50. Gomez M, Silvestri GA. Endobronchial ultrasound for the diagnosis and staging of lung cancer. Proc Am Thorac Soc 2009; 6:180.
  51. Ong P, Grosu H, Eapen GA, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for systematic nodal staging of lung cancer in patients with N0 disease by computed tomography and integrated positron emission tomography-computed tomography. Ann Am Thorac Soc 2015; 12:415.
  52. Bonifazi M, Zuccatosta L, Poidomani G, et al. Bullous pemphigoid with the unusual complication of tracheobronchial involvement. Chest 2013; 143:236.
  53. van der Heijden EH, Casal RF, Trisolini R, et al. Guideline for the acquisition and preparation of conventional and endobronchial ultrasound-guided transbronchial needle aspiration specimens for the diagnosis and molecular testing of patients with known or suspected lung cancer. Respiration 2014; 88:500.
  54. Annema JT, van Meerbeeck JP, Rintoul RC, et al. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial. JAMA 2010; 304:2245.
  55. Wallace MB, Pascual JM, Raimondo M, et al. Minimally invasive endoscopic staging of suspected lung cancer. JAMA 2008; 299:540.
  56. Light RW, Erozan YS, Ball WC Jr. Cells in pleural fluid. Their value in differential diagnosis. Arch Intern Med 1973; 132:854.
  57. Prakash UB, Reiman HM. Comparison of needle biopsy with cytologic analysis for the evaluation of pleural effusion: analysis of 414 cases. Mayo Clin Proc 1985; 60:158.
  58. Mentzer SJ, Swanson SJ, DeCamp MM, et al. Mediastinoscopy, thoracoscopy, and video-assisted thoracic surgery in the diagnosis and staging of lung cancer. Chest 1997; 112:239S.
  59. Menzies R, Charbonneau M. Thoracoscopy for the diagnosis of pleural disease. Ann Intern Med 1991; 114:271.
  60. Nguyen P, Feng JC, Chang KJ. Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (FNA) of liver lesions. Gastrointest Endosc 1999; 50:357.
  61. Uemura S, Yasuda I, Kato T, et al. Preoperative routine evaluation of bilateral adrenal glands by endoscopic ultrasound and fine-needle aspiration in patients with potentially resectable lung cancer. Endoscopy 2013; 45:195.
  62. Puli SR, Batapati Krishna Reddy J, Bechtold ML, et al. Endoscopic ultrasound: it's accuracy in evaluating mediastinal lymphadenopathy? A meta-analysis and systematic review. World J Gastroenterol 2008; 14:3028.
  63. Bodtger U, Vilmann P, Clementsen P, et al. Clinical impact of endoscopic ultrasound-fine needle aspiration of left adrenal masses in established or suspected lung cancer. J Thorac Oncol 2009; 4:1485.
  64. Blackhall F, Thatcher N, Booton R, Kerr K. The impact on the multidisciplinary team of molecular profiling for personalized therapy in non-small cell lung cancer. Lung Cancer 2013; 79:101.
Topic 88822 Version 28.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟