Clinical Evaluation 临床评价
As previously described, low-dose CT screening is recommended for asymptomatic select patients who are at high risk for lung cancer (see the NCCN Guidelines for Lung Cancer Screening, available at NCCN.org). For the 2017 update (Version 1), the NCCN Panel added a new algorithm for incidental lung nodules that are detected on CT scans; the workup and evaluation of these incidental lung nodules is described in the NSCLC algorithm (see Diagnostic Evaluation of Lung Nodules in this Discussion and the NCCN Guidelines for NSCLC).
After patients are confirmed to have NSCLC based on a pathologic diagnosis, a clinical evaluation needs to be done (see the NCCN Guidelines for NSCLC). In patients with symptoms, the clinical stage is initially determined from disease history (ie, cough, dyspnea, chest pain, weight loss) and physical examination together with a limited battery of tests (see Evaluation and Clinical Stage in the NCCN Guidelines for NSCLC). The NCCN Panel also recommends that smoking cessation advice, counseling, and pharmacotherapy be provided to patients. After the clinical stage is determined, the patient is assigned to one of the pathways that are defined by the stage, specific subdivision of the particular stage, and location of the tumor. Note that for some patients, diagnosis, staging, and surgical resection are done during the same operative procedure. A multidisciplinary evaluation should be done before treatment.
在患者病理确诊为NSCLC后，需要进行临床评估（见NSCLC NCCN指南）。在有症状的患者中，从病史（如，咳嗽、呼吸困难、胸痛、体重下降）和体格检查以及有限的系列检测数据初步确定临床分期（见NSCLC NCCN指南中的评估与临床分期）。NCCN小组还建议劝告患者戒烟、提供咨询服务和药物治疗。在确定临床分期后，将患者分配到根据分期、具体分期的细分期以及肿瘤部位所确定的路径中。注意，对于诊断、分期相同的患者，采取相同的手术过程手术切除。治疗前应进行多学科评价。
Additional Pretreatment Evaluation 治疗前的其他评估
As previously noted, evaluation of the mediastinal nodes is a key step in the further staging of the patient. FDG PET/CT scans can be used as an initial assessment of the hilar and mediastinal nodes (ie, to determine whether the N1, N2, or N3 nodes are positive for cancer, which is a key determinant of stage II and stage III disease); however, CT scans have known limitations for evaluating the extent of lymph node involvement in lung cancer (see Mediastinoscopy and Other Imaging Studies in this Discussion). Mediastinoscopy is the gold standard for evaluating mediastinal nodes. Thus, mediastinoscopy is encouraged as part of the initial evaluation, particularly if the results of imaging are not conclusive and the probability of mediastinal involvement is high (based on tumor size and location). Therefore, mediastinoscopy is appropriate for patients with T2 to T3 lesions even if the FDG PET/CT scan does not suggest mediastinal node involvement. Mediastinoscopy may also be appropriate to confirm mediastinal node involvement in patients with a positive FDG PET/CT scan. In patients with solid tumors less than 1 cm or for nonsolid tumors (ie, GGOs) less than 3 cm, pathologic mediastinal lymph node evaluation is not required if the nodes are FDG-PET/CT negative. Mediastinal evaluation can be considered in patients with clinical stage 1A disease (T1ab, N0). In patients with peripheral T2a, central T1ab, or T2 lesions with negative FDG PET/CT scans, the risk for mediastinal lymph node involvement is higher and mediastinoscopy and/or EUS-FNA and EBUS-TBNA are recommended (see Other Imaging Studies in this Discussion and the NCCN Guidelines for NSCLC).
正如先前指出的，纵隔淋巴结的评估是对患者进一步分期中的一个关键步骤。FDG PET/CT扫描可作为肺门与纵隔淋巴结的初步评估（即确定是N1、N2还是N3淋巴结肿瘤阳性，这是决定Ⅱ期和Ⅲ期疾病的关键）；不过，已知CT扫描评价肺癌淋巴结受累程度具有局限性（见本讨论中的纵隔镜检查和其他影像学检查）。纵隔镜检查是评估纵隔淋巴结的金标准。因此，鼓励纵隔镜检查作为初步评估，尤其是如果成像结果不能确定且纵隔受累的概率高（根据肿瘤的大小和位置）。因此，对于T2-T3的患者即使FDG PET/CT扫描没有提示纵隔淋巴结受累纵隔镜检查也是合适的。在FDG PET/CT扫描阳性的患者中，纵隔镜检查还适于证实纵隔淋巴结受累。在小于1cm的实性瘤或小于3cm的非实性肿瘤（即磨玻璃结节）患者中，如果FDG-PET/CT淋巴结阴性，纵隔淋巴结病理学评估不是必需的。对于临床1A期（T1abN0）的患者，可以考虑纵隔评估。在FDG PET/CT扫描阴性的周围型T2a、中心型T1ab或T2病变患者中，纵隔淋巴结转移的风险较高，建议纵隔镜检查和/或EUS-FNA和EBUS-TBNA（见本讨论与NSCLC NCCN指南中的其他影像学检查）。
Dillemans et al have reported a selective mediastinoscopy strategy, proceeding straight to thoracotomy without mediastinoscopy for T1 peripheral tumors without enlarged mediastinal lymph nodes on preoperative CT. This strategy resulted in a 16% incidence of positive N2 nodes discovered only at the time of thoracotomy. For identifying N2 disease, chest CT scans had sensitivity and specificity rates of 69% and 71%, respectively. However, using both the chest CT scan plus mediastinoscopy was significantly more accurate (89% vs. 71%) than using the chest CT scan alone for identifying N2 disease. When using CT scans, node positivity is based on the size of the lymph nodes. Therefore, the CT scan will miss small metastases that do not result in node enlargement. To address this issue, Arita et al specifically examined lung cancer metastases to normal size mediastinal lymph nodes in 90 patients and found an incidence of 16% (14/90) false-negative chest CT scans with histologic identification of occult N2 or N3 disease.
Bronchoscopy is used in diagnosis and local staging of both central and peripheral lung lesions and is recommended for pretreatment evaluation of stage I to IIIA tumors. However, in patients who present with a solitary pulmonary nodule where the suspicion of malignancy is high, surgical resection without prior invasive testing may be reasonable.
Other Imaging Studies 其他影像学检查
As previously mentioned, CT scans have known limitations for evaluating the extent of lymph node involvement in lung cancer. PET scans have been used to help evaluate the extent of disease and to provide more accurate staging. The NCCN Panel reviewed the diagnostic performance of CT and PET scans. The NCCN Panel believes that PET scans can play a role in the evaluation and more accurate staging of NSCLC, for example, in identifying stage I (peripheral and central T1–2, N0), stage II, stage III, and stage IV diseases. However, FDG PET/CT is even more sensitive and is recommended by NCCN. PET/CT is typically done from the skull base to the knees; whole body PET/CT may also be done.
The NCCN Panel assessed studies that examined the sensitivity and specificity of chest CT scans for mediastinal lymph node staging. Depending on the clinical scenario, a sensitivity of 40% to 65% and a specificity of 45% to 90% were reported. Because they detect tumor physiology, as opposed to anatomy, PET scans may be more sensitive than CT scans. Moreover, if postobstructive pneumonitis is present, there is little correlation between the size of the mediastinal lymph nodes and tumor involvement. Chin et al found that PET, when used to stage the mediastinal nodes, was 78% sensitive and 81% specific with a negative predictive value of 89%. Kernstine et al compared PET scan to CT scan for identifying N2 and N3 disease in NSCLC. The PET scan was found to be more sensitive than the CT scan in identifying mediastinal node disease (70% vs. 65%). FDG PET/CT has been shown to be useful in restaging patients after adjuvant therapy.
NCCN小组评估研究了胸部CT扫描对纵隔淋巴结分期的敏感性和特异性。取决于临床情况，报告的敏感性为40%-65%、特异性为45%-90%。因为PET扫描检测肿瘤生理学，而非解剖学，因此可能比CT扫描更敏感。此外，如果存在阻塞性肺炎，纵隔淋巴结大小与肿瘤浸润之间几乎没有相关性。Chin等发现，当PET用于纵隔淋巴结的分期时，敏感性是78%，特异性是81%，阴性预测值为89%。Kernstine等对PET扫描与CT扫描用于识别NSCLC N2和N3疾病进行了比较。认为在识别纵隔淋巴结病变方面PET比CT更敏感（70%对65%）。已证明FDG PET/CT在患者辅助治疗后的再分期方面是有用的。
When patients with early-stage disease are accurately staged using FDG PET/CT, inappropriate surgery is avoided. However, positive FDG PET/CT scan findings for distant disease need pathologic or other radiologic confirmation (eg, MRI of bone). If the FDG PET/CT scan is positive in the mediastinum, the lymph node status needs pathologic confirmation. Transesophageal EUS-FNA and EBUS-TBNA have proven useful to stage patients or to diagnose mediastinal lesions; these techniques can be used instead of invasive staging procedures in select patients. When compared with CT and PET, EBUS-TBNA has a high sensitivity and specificity for staging mediastinal and hilar lymph nodes in patients with lung cancer. In patients with positive nodes on CT or PET, EBUS-TNBA can be used to clarify the results. However, in patients with negative findings on EBUS-TNBA, conventional mediastinoscopy can be done to confirm the results. Note that EBUS is also known as endosonography.
当早期患者使用FDG PET/CT准确分期时，可避免不适当的手术。不过，对于FDG PET/CT扫描发现的阳性远隔病变需要病理或其他影像学（如，骨MRI）确认。如果FDG PET/CT扫描纵隔淋巴结阳性，该淋巴结情况需要病理学证实。已经证明经食道EUS-FNA和EBUS-TBNA对于患者分期或诊断纵隔病变是有用的；在选择的患者中这些技术可以用来代替侵袭性分期程序。与CT和PET相比，EBUS-TBNA对肺癌患者的纵隔及肺门淋巴结分期具有高敏感性和特异性。CT或PET淋巴结阳性患者，可以用EBUS-TNBA来澄清结果。然而，在EBUS-TNBA结果阴性的患者中，可进行常规纵隔镜检查以证实该结果。注意，EBUS亦称为腔内超声检查。
The routine use of bone scans (to exclude bone metastases) is not recommended. Brain MRI (with contrast), to rule out asymptomatic brain metastases, is recommended for patients with stage II, III, and IV disease to rule out metastatic disease if aggressive combined-modality therapy is being considered. Patients with stage IB NSCLC are less likely to have brain metastases; therefore, brain MRI is optional in this setting and can be considered for select patients at high risk (eg, tumors greater than 5 cm, central location). If brain MRI cannot be done, then CT of the head with contrast is an option. Note that PET scans are not recommended for assessing whether brain metastases are present (see the NCCN Guidelines for Central Nervous System Cancers, available at NCCN.org).