Non-Small Cell Lung Cancer Treatment (PDQ®) 2/5 —Health Professional Version - National Cancer Institute

Non-Small Cell Lung Cancer Treatment (PDQ®)—Health Professional Version - National Cancer Institute

Non-Small Cell Lung Cancer Treatment (PDQ®)–Health Professional Version

Stage Information for NSCLC

In This Section

• Background
• Staging Evaluation
  • Evaluation of mediastinal lymph node metastasis
  • Evaluation of brain metastasis
  • Evaluation of distant metastasis other than the brain
• The Revised International System for Staging Lung Cancer
• AJCC Stage Groupings and TNM Definitions

Background

In non-small cell lung cancer (NSCLC), the determination of stage has important therapeutic and prognostic implications. Careful initial diagnostic evaluation to define the location and to determine the extent of primary and metastatic tumor involvement is critical for the appropriate care of patients.

In general, symptoms, physical signs, laboratory findings, or perceived risk of distant metastasis lead to an evaluation for distant metastatic disease. Additional tests such as bone scans and computed tomography (CT)/magnetic resonance imaging (MRI) of the brain may be performed if initial assessments suggest metastases or if patients with stage III disease are under consideration for aggressive local and combined modality treatments.

Stage has a critical role in the selection of therapy. The stage of disease is based on a combination of clinical factors and pathological factors.[1] The distinction between clinical stage and pathological stage should be considered when evaluating reports of survival outcome.

Procedures used to determine staging include the following:

• History.
• Physical examination.
• Routine laboratory evaluations.
• Chest x-ray.
• Chest CT scan with infusion of contrast material.
• Fluorine F 18-fludeoxyglucose positron emission tomography (18F-FDG PET) scanning.

Procedures used to obtain tissue samples include bronchoscopy, mediastinoscopy, or anterior mediastinotomy. Pathological staging of NSCLC requires the following:

• Examination of the tumor.
• Resection margins.
• Lymph nodes.

Prognostic and treatment decisions are based on some of the following factors:

• Knowledge of histologic type.
• Tumor size and location.
• Involvement of pleura.
• Surgical margins.
• Status and location of lymph nodes by station.
• Tumor grade.
• Lymphovascular invasion.

At diagnosis, patients with NSCLC can be divided into the following three groups that reflect both the extent of the disease and the treatment approach:

1. Surgically resectable disease (generally stage I, stage II, and selected stage III tumors).
   • Has the best prognosis, which depends on a variety of tumor and host factors.
   • Patients with resectable disease who have medical contraindications to surgery are candidates for curative radiation therapy.
   • Postoperative cisplatin-based combination chemotherapy may provide a survival advantage for patients with resected stage II or stage IIIA NSCLC.
2. Locally (T3–T4) and/or regionally (N2–N3) advanced disease.
   • Has a diverse natural history.
   • Selected patients with locally advanced tumors may benefit from combined modality treatments.
   • Patients with unresectable or N2–N3 disease are treated with radiation therapy in combination with chemotherapy.
   • Selected patients with T3 or N2 disease can be treated effectively with surgical resection and either preoperative or postoperative chemotherapy or chemoradiation therapy.
3. Distant metastatic disease (includes distant metastases [M1] that were found at the time of diagnosis).
   • May be treated with radiation therapy or chemotherapy for palliation of symptoms of the primary tumor.
   • Patients with good performance status, women, and patients with distant metastases confined to a single site live longer than others.[2]
   • Platinum-based chemotherapy has been associated with short-term palliation of symptoms and with a survival advantage.
   • Currently, no single chemotherapy regimen can be recommended for routine use.
   • Patients previously treated with platinum combination chemotherapy may derive symptom control and survival benefit from docetaxel, pemetrexed, or epidermal growth factor receptor inhibitors.

Staging Evaluation

Evaluation of mediastinal lymph node metastasis

Surgical evaluation

Surgical staging of the mediastinum is considered standard if accurate evaluation of the nodal status is needed to determine therapy.

Accurate staging of the mediastinal lymph nodes provides important prognostic information.

Evidence (nodal status):

1. The association between survival and the number of examined lymph nodes during surgery for patients with stage I NSCLC treated with definitive surgical resection was assessed from the population-based Surveillance, Epidemiology, and End Results (SEER) database for the period from 1990 to 2000.[3] A total of 16,800 patients were included in the study.
   • The overall survival analysis for patients without radiation therapy demonstrated that in comparison with the reference group (one to four lymph nodes), patients with five to eight lymph nodes examined during surgery had a modest but statistically significant increase in survival, with a proportionate hazard ratio (HR) of 0.90 (95% confidence interval [CI], 0.84–0.97). For patients with 9 to 12 examined lymph nodes, the HR was 0.86 (95% CI, 0.79–0.95), and for patients with 13 to 16 examined lymph nodes, the HR was 0.78 (95% CI, 0.68–0.90). There appeared to be no incremental improvement after evaluating more than 16 lymph nodes. The corresponding results for lung cancer–specific mortality and for patients receiving radiation therapy were not substantially different.
   • These results indicate that patient survival following resection for NSCLC is associated with the number of lymph nodes evaluated during surgery. Because this is most likely the result of a reduction-of-staging error, namely, a decreased likelihood of missing positive lymph nodes with an increasing number of lymph nodes sampled, it suggests that an evaluation of nodal status should include 11 to 16 lymph nodes.

CT imaging

CT scanning is primarily used for determining the size of the tumor. The CT scan should extend inferiorly to include the liver and adrenal glands. MRI scans of the thorax and upper abdomen do not appear to yield advantages over CT scans.[4]

Evidence (CT scan):

1. A systematic review of the medical literature relating to the accuracy of CT scanning for noninvasive staging of the mediastinum in patients with lung cancer has been conducted. In the 35 studies published between 1991 and June 2006, 5,111 evaluable patients were identified. Almost all studies specified that CT scanning was performed following the administration of intravenous contrast material and that a positive test result was defined as the presence of one or more lymph nodes that measured larger than 1 cm on the short-axis diameter.[5]
   • The median prevalence of mediastinal metastasis was 28% (range, 18%–56%).
   • The pooled sensitivity and specificity of CT scanning for identifying mediastinal lymph node metastasis were 51% (95% CI, 47%–54%) for sensitivity and 86% (95% CI, 84%–88%) for specificity. Corresponding positive (3.4%) and negative (0.6%) likelihood ratios were provided.
2. The results from the systematic review are similar to those of a large meta-analysis that reported the median sensitivity and specificity of CT scanning for identifying malignant mediastinal nodes as 61% for sensitivity and 79% for specificity.[6]
3. An earlier meta-analysis reported an average sensitivity rate of 64% and specificity rate of 74%.[7]

18F-FDG PET scanning

The wider availability and use of 18F-FDG PET scanning for staging has modified the approach to staging mediastinal lymph nodes and distant metastases.

Randomized trials evaluating the utility of 18F-FDG PET scanning in potentially resectable NSCLC report conflicting results in terms of the relative reduction in the number of noncurative thoracotomies.

Although the current evidence is conflicting, 18F-FDG PET scanning may improve results of early-stage lung cancer by identifying patients who have evidence of metastatic disease that is beyond the scope of surgical resection and that is not evident by standard preoperative staging procedures.

Evidence (18F-FDG PET scan):

1. A systematic review, an expansion of a health technology assessment conducted in 2001 by the Institute for Clinical and Evaluative Sciences, evaluated the accuracy and utility of 18F-FDG PET scanning in the diagnosis and staging of lung cancer.[8] Through a systematic search of the literature, 12 evidence summary reports and 15 prospective studies of the diagnostic accuracy of 18F-FDG PET scanning were identified. 18F-FDG PET scanning appears to be superior to CT imaging for mediastinal staging in NSCLC. 18F-FDG PET scanning also appears to have high sensitivity and reasonable specificity for differentiating benign from malignant lesions as small as 1 cm.
2. A systematic review of the medical literature relating to the accuracy of 18F-FDG PET scanning for noninvasive staging of the mediastinum in patients with lung cancer identified 44 studies published between 1994 and 2006 with 2,865 evaluable patients.[5] The median prevalence of mediastinal metastases was 29% (range, 5%–64%). Pooled estimates of sensitivity and specificity for identifying mediastinal metastasis were 74% (95% CI, 69%–79%) for sensitivity and 85% (95% CI, 82%–88%) for specificity. Corresponding positive (4.9%) and negative (0.3%) likelihood ratios were provided for mediastinal staging with 18F-FDG PET scanning. These findings demonstrated that 18F-FDG PET scanning is more accurate than CT scanning for staging of the mediastinum in patients with lung cancer.

Cost effectiveness of 18F-FDG PET scanning

Decision analyses demonstrate that 18F-FDG PET scanning may reduce the overall costs of medical care by identifying patients with falsely negative CT scans in the mediastinum or otherwise undetected sites of metastases.[9-11] Studies concluded that the money saved by forgoing mediastinoscopy in 18F-FDG PET-positive mediastinal lesions was not justified because of the unacceptably high number of false-positive results.[9-11] A randomized study found that the addition of 18F-FDG PET scanning to conventional staging was associated with significantly fewer thoracotomies.[12] A second randomized trial evaluating the impact of 18F-FDG PET scanning on clinical management found that 18F-FDG PET scanning provided additional information regarding appropriate stage but did not lead to significantly fewer thoracotomies.[13]

Combination of CT imaging and 18F-FDG PET scanning

The combination of CT imaging and 18F-FDG PET scanning has greater sensitivity and specificity than CT imaging alone.[14]

Evidence (CT/18F-FDG PET scan):

1. If there is no evidence of distant metastatic disease on CT scan, 18F-FDG PET scanning complements CT scan staging of the mediastinum. Numerous nonrandomized studies of 18F-FDG PET scanning have evaluated mediastinal lymph nodes using surgery (i.e., mediastinoscopy and/or thoracotomy with mediastinal lymph node dissection) as the gold standard of comparison.
2. In a meta-analysis evaluating the conditional test performance of 18F-FDG PET scanning and CT scanning, the median sensitivity and specificity of 18F-FDG PET scans were reported as 100% for sensitivity and 78% for specificity in patients with enlarged lymph nodes.[6] 18F-FDG PET scanning is considered very accurate in identifying malignant nodal involvement when lymph nodes are enlarged. However, 18F-FDG PET scanning will falsely identify a malignancy in approximately one-fourth of patients with lymph nodes that are enlarged for other reasons, usually as a result of inflammation or infection.[15,16]
3. The median sensitivity and specificity of 18F-FDG PET scanning in patients with normal-sized mediastinal lymph nodes were 82% for sensitivity and 93% for specificity.[6] These data indicate that nearly 20% of patients with normal-sized lymph nodes but with malignant involvement had falsely negative 18F-FDG PET scan findings.

For patients with clinically operable NSCLC, the recommendation is for a biopsy of mediastinal lymph nodes that were found to be larger than 1 cm in shortest transverse axis on chest CT scan or were found to be positive on 18F-FDG PET scan. Negative 18F-FDG PET scanning does not preclude biopsy of radiographically enlarged mediastinal lymph nodes. Mediastinoscopy is necessary for the detection of cancer in mediastinal lymph nodes when the results of the CT scan and 18F-FDG PET scan do not corroborate each other.

Evaluation of brain metastasis

Patients at risk for brain metastases may be staged with CT or MRI scans. One study randomly assigned 332 patients with potentially operable NSCLC and no neurological symptoms to brain CT or MRI imaging to detect occult brain metastasis before lung surgery. MRI showed a trend towards a higher preoperative detection rate than CT scan (P= .069), with an overall detection rate of approximately 7% from pretreatment to 12 months after surgery.[17] Patients with stage I or stage II disease had a detection rate of 4% (i.e., eight detections out of 200 patients); however, individuals with stage III disease had a detection rate of 11.4% (i.e., 15 detections out of 132 patients). The mean maximal diameter of the brain metastases was significantly smaller in the MRI group. Whether the improved detection rate of MRI translates into improved outcome remains unknown. Not all patients are able to tolerate MRI, and for these patients contrast-enhanced CT scan is a reasonable substitute.

Evaluation of distant metastasis other than the brain

Numerous nonrandomized, prospective, and retrospective studies have demonstrated that 18F-FDG PET scanning seems to offer diagnostic advantages over conventional imaging in staging distant metastatic disease; however, standard 18F-FDG PET scans have limitations. 18F-FDG PET scans may not extend below the pelvis and may not detect bone metastases in the long bones of the lower extremities. Because the metabolic tracer used in 18F-FDG PET scanning accumulates in the brain and urinary tract, 18F-FDG PET scanning is not reliable for detection of metastases in these sites.[17]

The Revised International System for Staging Lung Cancer

The Revised International System for Staging Lung Cancer, based on information from a clinical database of more than 5,000 patients, was adopted in 2010 by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer.[18,19] These revisions provide greater prognostic specificity for patient groups; however, the correlation between stage and prognosis predates the widespread availability of PET imaging.

AJCC Stage Groupings and TNM Definitions

The AJCC has designated staging by TNM (tumor, node, metastasis) classification to define NSCLC.[19]

Table 1. Definitions of TNM Occult Carcinomaa

Stage	TNM	Description
aReprinted with permission from AJCC: Lung. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 431–56.
Occult carcinoma	TX, N0, M0	TX = Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.
T = primary tumor; N = regional lymph node; M = distant metastasis.

Table 2. Definitions of TNM Stage 0a

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Lung. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 431–56.
0	Tis, N0, M0	Tis = Carcinoma in situ; SCIS =Squamous cell carcinoma in situ; AIS: Adenocarcinoma in situ; Adenocarcinoma with pure lepidic pattern, ≤3 cm in greatest dimension.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.

Table 3. Definitions of TNM Stages IA1, IA2, IA3, and IBa

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Lung. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 431–56.
IA1	T1mi, N0, M0	T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1mi = Minimally invasive adenocarcinoma: Adenocarcinoma (≤3 cm in greatest dimension) with a predominantly lepidic pattern and ≤5 mm invasion in greatest dimension.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.
	T1a, N0, M0	T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1mi = Minimally invasive adenocarcinoma: adenocarcinoma (≤3 cm in greatest dimension) with a predominantly lepidic pattern and ≤5 mm invasion in greatest dimension.
		–T1a = Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.
IA2	T1b, N0, M0	T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1mi = Minimally invasive adenocarcinoma: adenocarcinoma (≤3 cm in greatest dimension) with a predominantly lepidic pattern and ≤5 mm invasion in greatest dimension.
		–T1a = Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon.
		–T1b = Tumor >1 cm but ≤2 cm in greatest dimension.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.
IA3	T1c, N0, M0	T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1mi = Minimally invasive adenocarcinoma: adenocarcinoma (≤3 cm in greatest dimension) with a predominantly lepidic pattern and ≤5 mm invasion in greatest dimension.
		–T1a = Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon.
		–T1b = Tumor >1 cm but ≤2 cm in greatest dimension.
		–T1c = Tumor >2 cm but ≤3 cm in greatest dimension.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.
IB	T2a, N0, M0	T2 = Tumor >3 cm but ≤5 cm or having any of the following features: involves the main bronchus regardless of distance to the carina, but without involvement of the carina; invades visceral pleura (PL1 or PL2); associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung. T2 tumors with these features are classified as T2a if ≤4 cm or if the size cannot be determined and T2b if >4 cm but ≤5 cm.
		–T2a = Tumor >3 cm but ≤4 cm in greatest dimension.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.

Table 4. Definitions of TNM Stages IIA and IIBa

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Lung. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 431–56.
IIA	T2b, N0, M0	T2 = Tumor >3 cm but ≤5 cm or having any of the following features: involves the main bronchus regardless of distance to the carina, but without involvement of the carina; invades visceral pleura (PL1 or PL2); associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung. T2 tumors with these features are classified as T2a if ≤4 cm or if the size cannot be determined and T2b if >4 cm but ≤5 cm.
		–T2a = Tumor >3 cm but ≤4 cm in greatest dimension.
		–T2b = Tumor >4 cm but ≤5 cm in greatest dimension.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.
IIB	T1a, N1, M0	T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1a = Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon.
		N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
		M0 = No distant metastasis.
	T1b, N1, M0	T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1a = Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon.
		–T1b = Tumor >1 cm but ≤2 cm in greatest dimension.
		N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
		M0 = No distant metastasis.
	T1c, N1, M0	T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1a = Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon.
		–T1b = Tumor >1 cm but ≤2 cm in greatest dimension.
		–T1c = Tumor >2 cm but ≤3 cm in greatest dimension.
		N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
		M0 = No distant metastasis.
	T2a, N1, M0	T2 = Tumor >3 cm but ≤5 cm or having any of the following features: involves the main bronchus regardless of distance to the carina, but without involvement of the carina; invades visceral pleura (PL1 or PL2); associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung. T2 tumors with these features are classified as T2a if ≤4 cm or if the size cannot be determined and T2b if >4 cm but ≤5 cm.
		–T2a = Tumor >3 cm but ≤4 cm in greatest dimension.
		N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
		M0 = No distant metastasis.
	T2b, N1, M0	T2 = Tumor >3 cm but ≤5 cm or having any of the following features: involves the main bronchus regardless of distance to the carina, but without involvement of the carina; invades visceral pleura (PL1 or PL2); associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung. T2 tumors with these features are classified as T2a if ≤4 cm or if the size cannot be determined and T2b if >4 cm but ≤5 cm.
		–T2a = Tumor >3 cm but ≤4 cm in greatest dimension.
		–T2b = Tumor >4 cm but ≤5 cm in greatest dimension.
		N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
		M0 = No distant metastasis.
	T3, N0, M0	T3 = Tumor >5 cm but ≤7 cm in greatest dimension or directly invading any of the following: parietal pleura (PL3), chest wall (Including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.

Table 5. Definitions of TNM Stages IIIA, IIIB, and IIICa

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Lung. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 431–56.
IIIA	T1a, N2, M0	T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1a = Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon.
		N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
		M0 = No distant metastasis.
	T1b, N2, M0	T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1a = Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon.
		–T1b = Tumor >1 cm but ≤2 cm in greatest dimension.
		N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
		M0 = No distant metastasis.
	T1c, N2, M0	T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1a = Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon.
		–T1b = Tumor >1 cm but ≤2 cm in greatest dimension.
		–T1c = Tumor >2 cm but ≤3 cm in greatest dimension.
		N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
		M0 = No distant metastasis.
	T2a, N2, M0	T2 = Tumor >3 cm but ≤5 cm or having any of the following features: involves the main bronchus regardless of distance to the carina, but without involvement of the carina; invades visceral pleura (PL1 or PL2); associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung. T2 tumors with these features are classified as T2a if ≤4 cm or if the size cannot be determined and T2b if >4 cm but ≤5 cm.
		–T2a = Tumor >3 cm but ≤4 cm in greatest dimension.
		N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
		M0 = No distant metastasis.
	T2b, N2, M0	T2 = Tumor >3 cm but ≤5 cm or having any of the following features: involves the main bronchus regardless of distance to the carina, but without involvement of the carina; invades visceral pleura (PL1 or PL2); associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung. T2 tumors with these features are classified as T2a if ≤4 cm or if the size cannot be determined and T2b if >4 cm but ≤5 cm.
		–T2a = Tumor >3 cm but ≤4 cm in greatest dimension.
		–T2b = Tumor >4 cm but ≤5 cm in greatest dimension.
		N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
		M0 = No distant metastasis.
	T3, N1, M0	T3 = Tumor >5 cm but ≤7 cm in greatest dimension or directly invading any of the following: parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary.
		N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
		M0 = No distant metastasis.
	T4, N0, M0	T4 = Tumor >7 cm or tumor of any size invading one or more of the following: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe different from that of the primary.
		N0 = No regional lymph node metastasis.
		M0 = No distant metastasis.
	T4, N1, M0	T4 = Tumor >7 cm or tumor of any size invading one or more of the following: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe different from that of the primary.
		N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
		M0 = No distant metastasis.
IIIB	T1a, N3, M0	T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1a = Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon.
		N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
		M0 = No distant metastasis.
	T1b, N3, M0	T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1a = Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon.
		–T1b = Tumor >1 cm but ≤2 cm in greatest dimension.
		N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
		M0 = No distant metastasis.
	T1c, N3, M0	T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1a = Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon.
		–T1b = Tumor >1 cm but ≤2 cm in greatest dimension.
		–T1c = Tumor >2 cm but ≤3 cm in greatest dimension.
		N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
		M0 = No distant metastasis.
	T2a, N3, M0	T2 = Tumor >3 cm but ≤5 cm or having any of the following features: involves the main bronchus regardless of distance to the carina, but without involvement of the carina; invades visceral pleura (PL1 or PL2); associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung. T2 tumors with these features are classified as T2a if ≤4 cm or if the size cannot be determined and T2b if >4 cm but ≤5 cm.
		–T2a = Tumor >3 cm but ≤4 cm in greatest dimension.
		N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
		M0 = No distant metastasis.
	T2b, N3, M0	T2 = Tumor >3 cm but ≤5 cm or having any of the following features: involves the main bronchus regardless of distance to the carina, but without involvement of the carina; invades visceral pleura (PL1 or PL2); associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung. T2 tumors with these features are classified as T2a if ≤4 cm or if the size cannot be determined and T2b if >4 cm but ≤5 cm.
		–T2a = Tumor >3 cm but ≤4 cm in greatest dimension.
		–T2b = Tumor >4 cm but ≤5 cm in greatest dimension.
		N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
		M0 = No distant metastasis.
	T3, N2, M0	T3 = Tumor >5 cm but ≤7 cm in greatest dimension or directly invading any of the following: parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary.
		N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
		M0 = No distant metastasis.
	T4, N2, M0	T4 = Tumor >7 cm or tumor of any size invading one or more of the following: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe different from that of the primary.
		N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
		M0 = No distant metastasis.
IIIC	T3, N3, M0	T3 = Tumor >5 cm but ≤7 cm in greatest dimension or directly invading any of the following: parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary.
		N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
		M0 = No distant metastasis.
	T4, N3, M0	T4 = Tumor >7 cm or tumor of any size invading one or more of the following: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe different from that of the primary.
		N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
		M0 = No distant metastasis.

Table 6. Definitions of TNM Stages IV, IVA, and IVBa

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
aReprinted with permission from AJCC: Lung. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 431–56.
IV	Any T, Any N, M1	TX = Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy.
		T0 = No evidence of primary tumor.
		Tis = carcinoma in situ; SCIS = squamous cell carcinoma in situ; AIS = adenocarcinoma in situ: Adenocarcinoma with pure lepidic pattern, ≤3 cm in greatest dimension.
		T1 = Tumor ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus).
		–T1mi = Minimally invasive adenocarcinoma: Adenocarcinoma (≤3 cm in greatest dimension) with a predominantly lepidic pattern and ≤5 mm invasion in greatest dimension.
		–T1a = Tumor ≤1 cm in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon.
		–T1b = Tumor >1 cm but ≤2 cm in greatest dimension.
		–T1c = Tumor >2 cm but ≤3 cm in greatest dimension.
		T2 = Tumor >3 cm but ≤5 cm or having any of the following features: involves the main bronchus regardless of distance to the carina, but without involvement of the carina; invades visceral pleura (PL1 or PL2); associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung. T2 tumors with these features are classified as T2a if ≤4 cm or if the size cannot be determined and T2b if >4 cm but ≤5 cm.
		–T2a = Tumor >3 cm but ≤4 cm in greatest dimension.
		–T2b = Tumor >4 cm but ≤5 cm in greatest dimension.
		T3 = Tumor >5 cm but ≤7 cm in greatest dimension or directly invading any of the following: parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary.
		T4 = Tumor >7 cm or tumor of any size invading one or more of the following: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe different from that of the primary.
		NX = Regional lymph nodes cannot be assessed.
		N0 = No regional lymph node metastasis.
		N1 = Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension.
		N2 = Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).
		N3 = Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).
		M1 = Distant metastasis.
IVA	Any T, Any N, M1a	Any T = See T descriptions above in Any T, Any N, M1.
		Any N = See N descriptions above in Any T, Any N, M1.
		M1 = Distant metastasis.
		–M1a = Separate tumor nodule(s) in a contralateral lobe; tumor with pleural or pericardial nodules or malignant pleural or pericardial effusion. Most pleural (pericardial) effusions with lung cancer are a result of the tumor. In a few patients, however, multiple microscopic examinations of pleural (pericardial) fluid are negative for tumor, and the fluid is nonbloody and not an exudate. If these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging descriptor.
	Any T, Any N, M1b	Any T = See T descriptions above in Any T, Any N, M1.
		Any N = See N descriptions above in Any T, Any N, M1.
		M1 = Distant metastasis.
		–M1a = Separate tumor nodule(s) in a contralateral lobe; tumor with pleural or pericardial nodules or malignant pleural or pericardial effusion. Most pleural (pericardial) effusions with lung cancer are a result of the tumor. In a few patients, however, multiple microscopic examinations of pleural (pericardial) fluid are negative for tumor, and the fluid is nonbloody and not an exudate. If these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging descriptor.
		–M1b = Single extrathoracic metastases in a single organ (including involvement of a single nonregional node).
IVB	Any T, Any N, M1c	Any T = See T descriptions above in Any T, Any N, M1.
		Any N = See N descriptions above in Any T, Any N, M1.
		M1 = Distant metastasis.
		–M1a = Separate tumor nodule(s) in a contralateral lobe; tumor with pleural or pericardial nodules or malignant pleural or pericardial effusion. Most pleural (pericardial) effusions with lung cancer are a result of the tumor. In a few patients, however, multiple microscopic examinations of pleural (pericardial) fluid are negative for tumor, and the fluid is nonbloody and not an exudate. If these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging descriptor.
		–M1b = Single extrathoracic metastases in a single organ (including involvement of a single nonregional node).
		–M1c = Multiple extrathoracic metastases in a single organ or in multiple organs.

References

1. Pfister DG, Johnson DH, Azzoli CG, et al.: American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol 22 (2): 330-53, 2004. [PUBMED Abstract]
2. Albain KS, Crowley JJ, LeBlanc M, et al.: Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience. J Clin Oncol 9 (9): 1618-26, 1991. [PUBMED Abstract]
3. Ludwig MS, Goodman M, Miller DL, et al.: Postoperative survival and the number of lymph nodes sampled during resection of node-negative non-small cell lung cancer. Chest 128 (3): 1545-50, 2005. [PUBMED Abstract]
4. Webb WR, Gatsonis C, Zerhouni EA, et al.: CT and MR imaging in staging non-small cell bronchogenic carcinoma: report of the Radiologic Diagnostic Oncology Group. Radiology 178 (3): 705-13, 1991. [PUBMED Abstract]
5. Toloza EM, Harpole L, McCrory DC: Noninvasive staging of non-small cell lung cancer: a review of the current evidence. Chest 123 (1 Suppl): 137S-146S, 2003. [PUBMED Abstract]
6. Gould MK, Kuschner WG, Rydzak CE, et al.: Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis. Ann Intern Med 139 (11): 879-92, 2003. [PUBMED Abstract]
7. Dwamena BA, Sonnad SS, Angobaldo JO, et al.: Metastases from non-small cell lung cancer: mediastinal staging in the 1990s--meta-analytic comparison of PET and CT. Radiology 213 (2): 530-6, 1999. [PUBMED Abstract]
8. Ung YC, Maziak DE, Vanderveen JA, et al.: 18Fluorodeoxyglucose positron emission tomography in the diagnosis and staging of lung cancer: a systematic review. J Natl Cancer Inst 99 (23): 1753-67, 2007. [PUBMED Abstract]
9. Dietlein M, Weber K, Gandjour A, et al.: Cost-effectiveness of FDG-PET for the management of potentially operable non-small cell lung cancer: priority for a PET-based strategy after nodal-negative CT results. Eur J Nucl Med 27 (11): 1598-609, 2000. [PUBMED Abstract]
10. Scott WJ, Shepherd J, Gambhir SS: Cost-effectiveness of FDG-PET for staging non-small cell lung cancer: a decision analysis. Ann Thorac Surg 66 (6): 1876-83; discussion 1883-5, 1998. [PUBMED Abstract]
11. Gambhir SS, Hoh CK, Phelps ME, et al.: Decision tree sensitivity analysis for cost-effectiveness of FDG-PET in the staging and management of non-small-cell lung carcinoma. J Nucl Med 37 (9): 1428-36, 1996. [PUBMED Abstract]
12. van Tinteren H, Hoekstra OS, Smit EF, et al.: Effectiveness of positron emission tomography in the preoperative assessment of patients with suspected non-small-cell lung cancer: the PLUS multicentre randomised trial. Lancet 359 (9315): 1388-93, 2002. [PUBMED Abstract]
13. Viney RC, Boyer MJ, King MT, et al.: Randomized controlled trial of the role of positron emission tomography in the management of stage I and II non-small-cell lung cancer. J Clin Oncol 22 (12): 2357-62, 2004. [PUBMED Abstract]
14. Vansteenkiste JF, Stroobants SG, De Leyn PR, et al.: Lymph node staging in non-small-cell lung cancer with FDG-PET scan: a prospective study on 690 lymph node stations from 68 patients. J Clin Oncol 16 (6): 2142-9, 1998. [PUBMED Abstract]
15. Roberts PF, Follette DM, von Haag D, et al.: Factors associated with false-positive staging of lung cancer by positron emission tomography. Ann Thorac Surg 70 (4): 1154-9; discussion 1159-60, 2000. [PUBMED Abstract]
16. Liewald F, Grosse S, Storck M, et al.: How useful is positron emission tomography for lymphnode staging in non-small-cell lung cancer? Thorac Cardiovasc Surg 48 (2): 93-6, 2000. [PUBMED Abstract]
17. Yokoi K, Kamiya N, Matsuguma H, et al.: Detection of brain metastasis in potentially operable non-small cell lung cancer: a comparison of CT and MRI. Chest 115 (3): 714-9, 1999. [PUBMED Abstract]
18. Mountain CF: Revisions in the International System for Staging Lung Cancer. Chest 111 (6): 1710-7, 1997. [PUBMED Abstract]
19. Lung. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 431–56.

Treatment Option Overview for NSCLC

In This Section

• Follow-Up
• Current Clinical Trials

In non-small cell lung cancer (NSCLC), results of standard treatment are poor except for the most localized cancers. All newly diagnosed patients with NSCLC are potential candidates for studies evaluating new forms of treatment.

Surgery is potentially the most curative therapeutic option for this disease. Postoperative chemotherapy may provide an additional benefit to patients with resected NSCLC. Radiation therapy combined with chemotherapy can produce a cure in a small number of patients and can provide palliation in most patients. Prophylactic cranial irradiation may reduce the incidence of brain metastases, but there is no evidence of a survival benefit and the effect of prophylactic cranial irradiation on quality of life is not known.[1,2] In patients with advanced-stage disease, chemotherapy or epidermal growth factor receptor (EGFR) kinase inhibitors offer modest improvements in median survival, although overall survival is poor.[3,4]

Chemotherapy has produced short-term improvement in disease-related symptoms in patients with advanced NSCLC. Several clinical trials have attempted to assess the impact of chemotherapy on tumor-related symptoms and quality of life. In total, these studies suggest that tumor-related symptoms may be controlled by chemotherapy without adversely affecting overall quality of life;[5,6] however, the impact of chemotherapy on quality of life requires more study. In general, medically fit elderly patients with good performance status obtain the same benefits from treatment as younger patients.

The identification of gene mutations in lung cancer has led to the development of molecularly targeted therapy to improve the survival of subsets of patients with metastatic disease.[7] In particular, genetic abnormalities in EGFR, MAPK, and PI3K signaling pathways in subsets of NSCLC may define mechanisms of drug sensitivity and primary or acquired resistance to kinase inhibitors. EGFR mutations strongly predict the improved response rate and progression-free survival of inhibitors of EGFR. Fusions of ALK with EML4 and other genes form translocation products that occur in ranges from 3% to 7% in unselected NSCLC and are responsive to pharmacological inhibition of ALK by agents such as crizotinib. The MET oncogene encodes hepatocyte growth factor receptor. Amplification of this gene has been associated with secondary resistance to EGFR tyrosine kinase inhibitors.

The standard treatment options for each stage of NSCLC are presented in Table 7.

Table 7. Standard Treatment Options for NSCLC

Stage (TNM Staging Criteria)		Standard Treatment Options
ALK = anaplastic lymphoma kinase; BRAF = v-raf murine sarcoma viral oncogene homolog B1; EGFR = epidermal growth factor receptor; MEK = MAPK kinase 1; NSCLC = non-small cell lung cancer; PD-L1 = programmed death-ligand 1; TKI = tyrosine kinase inhibitors; TNM = T, size of tumor and any spread of cancer into nearby tissue; N, spread of cancer to nearby lymph nodes; M, metastasis or spread of cancer to other parts of body.
Occult NSCLC		Surgery
Stage 0 NSCLC		Surgery
		Endobronchial therapies
Stages IA and IB NSCLC		Surgery
		Radiation therapy
Stages IIA and IIB NSCLC		Surgery
		Adjuvant chemotherapy
		Neoadjuvant chemotherapy
		Radiation therapy
Stage IIIA NSCLC	Resected or resectable disease	Surgery
		Neoadjuvant therapy
		Adjuvant therapy
	Unresectable disease	Radiation therapy
		Chemoradiation therapy
	Superior sulcus tumors	Radiation therapy alone
		Surgery
		Chemoradiation therapy followed by surgery
	Tumors that invade the chest wall	Surgery
		Surgery and radiation therapy
		Radiation therapy alone
		Chemotherapy combined with radiation therapy and/or surgery
Stages IIIB and IIIC NSCLC		Sequential or concurrent chemotherapy and radiation therapy
		Radiation therapy dose escalation for concurrent chemoradiation
		Additional systemic therapy before or after concurrent chemotherapy and radiation therapy
		Radiation therapy alone
Newly Diagnosed Stage IV, Relapsed, and Recurrent NSCLC		Cytotoxic combination chemotherapy
		Combination chemotherapy with monoclonal antibodies
		Maintenance therapy following first-line chemotherapy (for patients with stable or responding disease after four cycles of platinum-based combination chemotherapy)
		EGFR tyrosine kinase inhibitors (for patients with EGFR mutations)
		ALK inhibitors (for patients with ALKtranslocations)
		ROS1 inhibitors (for patients with ROS1rearrangements)
		BRAFV600E and MEK inhibitors (for patients with BRAFV600E mutations
		Immune checkpoint inhibitor for PD-L1 expressing NSCLC.
		Local therapies and special considerations
Progressive Stage IV, Relapsed, and Recurrent NSCLC		Chemotherapy
		EGFR-directed therapy
		ALK-directed TKI
		ROS1-directed therapy
		BRAFV600E and MEK inhibitors (for patients with BRAFV600E mutations)
		Immunotherapy

In addition to the standard treatment options presented in Table 7, treatment options under clinical evaluation include the following:

• Combining local treatment (surgery).
• Regional treatment (radiation therapy).
• Systemic treatments (chemotherapy, immunotherapy, and targeted agents).
• Developing more effective systemic therapy.

Follow-Up

Several small series have reported that reduction in fluorine F 18-fludeoxyglucose positron emission tomography (18F-FDG PET) after chemotherapy, radiation therapy, or chemoradiation therapy correlates with pathological complete response and favorable prognosis.[8-15] Studies have used different timing of assessments, 18F-FDG PET parameters, and cutpoints to define 18F-FDG PET response. Reduction in maximum standardized uptake value (SUV) of higher than 80% predicted for complete pathological response with a sensitivity of 90%, specificity of 100%, and accuracy of 96%.[16] Median survival after resection was longer for patients with tumor SUV values of lower than 4 (56 months vs. 19 months).[15] Patients with complete metabolic response following radiation therapy were reported to have median survivals of 31 months versus 11 months.[17]

18F-FDG PET may be more sensitive and specific than computed tomography (CT) scan in assessing response to induction therapy. Optimal timing of imaging remains to be defined; however, one study suggested that greater sensitivity and specificity of 18F-FDG PET is achieved if repeat imaging is delayed until 30 days after radiation therapy.[16]

There is no clear role for routine posttreatment PET-CT scans.[18][Level of evidence: 3iiA]

Evidence (surveillance imaging after radiation therapy with or without chemotherapy):

1. A prospective multicenter trial led by the American College of Radiology Imaging Network (ACRIN) and the Radiation Therapy Oncology Group (RTOG) cooperative group (ACRIN 6668/RTOG 0235 [NCT00083083]) studied the role of posttreatment PET-CT at approximately 14 weeks (range, 12–16 weeks) to predict overall survival (OS) after standard-of-care concurrent chemotherapy and radiation therapy in 173 patients with stage III disease.
   • The primary endpoint was to determine the relationship between SUVpeak at a prespecified binary cutoff of SUVpeak 3.5 with OS.
   • The study demonstrated no association between OS and SUVpeak of 3.5 or lower compared with SUVpeak higher than 3.5 with 2-year OS estimates of 51% vs. 37% (P = 0.29).
   • Exploratory analyses showed associations between OS and SUVpeak as a continuous variable, and binary cutoffs of SUVpeak 5.0 and 7.0.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

1. Lester JF, MacBeth FR, Coles B: Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small-cell lung cancer: a Cochrane Review. Int J Radiat Oncol Biol Phys 63 (3): 690-4, 2005. [PUBMED Abstract]
2. Pöttgen C, Eberhardt W, Grannass A, et al.: Prophylactic cranial irradiation in operable stage IIIA non small-cell lung cancer treated with neoadjuvant chemoradiotherapy: results from a German multicenter randomized trial. J Clin Oncol 25 (31): 4987-92, 2007. [PUBMED Abstract]
3. Chemotherapy for non-small cell lung cancer. Non-small Cell Lung Cancer Collaborative Group. Cochrane Database Syst Rev (2): CD002139, 2000. [PUBMED Abstract]
4. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group. BMJ 311 (7010): 899-909, 1995. [PUBMED Abstract]
5. Spiro SG, Rudd RM, Souhami RL, et al.: Chemotherapy versus supportive care in advanced non-small cell lung cancer: improved survival without detriment to quality of life. Thorax 59 (10): 828-36, 2004. [PUBMED Abstract]
6. Clegg A, Scott DA, Hewitson P, et al.: Clinical and cost effectiveness of paclitaxel, docetaxel, gemcitabine, and vinorelbine in non-small cell lung cancer: a systematic review. Thorax 57 (1): 20-8, 2002. [PUBMED Abstract]
7. Pao W, Girard N: New driver mutations in non-small-cell lung cancer. Lancet Oncol 12 (2): 175-80, 2011. [PUBMED Abstract]
8. Curran WJ Jr, Paulus R, Langer CJ, et al.: Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst 103 (19): 1452-60, 2011. [PUBMED Abstract]
9. Fournel P, Robinet G, Thomas P, et al.: Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Français de Pneumo-Cancérologie NPC 95-01 Study. J Clin Oncol 23 (25): 5910-7, 2005. [PUBMED Abstract]
10. Zatloukal P, Petruzelka L, Zemanova M, et al.: Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study. Lung Cancer 46 (1): 87-98, 2004. [PUBMED Abstract]
11. Rowell NP, O'rourke NP: Concurrent chemoradiotherapy in non-small cell lung cancer. Cochrane Database Syst Rev (4): CD002140, 2004. [PUBMED Abstract]
12. Cerfolio RJ, Bryant AS, Winokur TS, et al.: Repeat FDG-PET after neoadjuvant therapy is a predictor of pathologic response in patients with non-small cell lung cancer. Ann Thorac Surg 78 (6): 1903-9; discussion 1909, 2004. [PUBMED Abstract]
13. Pöttgen C, Levegrün S, Theegarten D, et al.: Value of 18F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography in non-small-cell lung cancer for prediction of pathologic response and times to relapse after neoadjuvant chemoradiotherapy. Clin Cancer Res 12 (1): 97-106, 2006. [PUBMED Abstract]
14. Eschmann SM, Friedel G, Paulsen F, et al.: 18F-FDG PET for assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer. Eur J Nucl Med Mol Imaging 34 (4): 463-71, 2007. [PUBMED Abstract]
15. Hellwig D, Graeter TP, Ukena D, et al.: Value of F-18-fluorodeoxyglucose positron emission tomography after induction therapy of locally advanced bronchogenic carcinoma. J Thorac Cardiovasc Surg 128 (6): 892-9, 2004. [PUBMED Abstract]
16. Cerfolio RJ, Bryant AS: When is it best to repeat a 2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography scan on patients with non-small cell lung cancer who have received neoadjuvant chemoradiotherapy? Ann Thorac Surg 84 (4): 1092-7, 2007. [PUBMED Abstract]
17. Mac Manus MP, Hicks RJ, Matthews JP, et al.: Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small-cell lung cancer. J Clin Oncol 21 (7): 1285-92, 2003. [PUBMED Abstract]
18. Machtay M, Duan F, Siegel BA, et al.: Prediction of survival by [18F]fluorodeoxyglucose positron emission tomography in patients with locally advanced non-small-cell lung cancer undergoing definitive chemoradiation therapy: results of the ACRIN 6668/RTOG 0235 trial. J Clin Oncol 31 (30): 3823-30, 2013. [PUBMED Abstract]

Occult NSCLC Treatment

In This Section

• Standard Treatment Options for Occult NSCLC
• Current Clinical Trials

In occult lung cancer, a diagnostic evaluation often includes chest x-ray and selective bronchoscopy with close follow-up (e.g., computed tomography scan), when needed, to define the site and nature of the primary tumor; tumors discovered in this fashion are generally early stage and curable by surgery.

After discovery of the primary tumor, treatment involves establishing the stage of the tumor. Therapy is identical to that recommended for other non-small cell lung cancer (NSCLC) patients with similar-stage disease.

Standard Treatment Options for Occult NSCLC

Standard treatment options for occult NSCLC include the following:

1. Surgery.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.