Lung cancer staging the noninvasive tools

LUNG CANCER STAGING

ProfessorAbdulsalam Y Taha

School of MedicineUniversity of Sulaimani

Iraq https://sulaimaniu.academia.edu/AbdulsalamTaha

INTRODUCTION LUNG CANCER remains the leading cause

of cancer-related mortality in men and women in the United States, accounting for over 157,000 deaths annually.

Despite advances in imaging, lung cancer is often detected when the disease has spread from the primary tumour to regional lymph nodes or distant sites.

04/08/23 2Prof. Abdulsalam Y Taha

INTRODUCTION…

Appropriate therapy is dependent on accurate staging to identify those patients who are surgical candidates and those patients for whom chemotherapy and radiation therapy is indicated.

In this review, the current staging system for lung cancer is discussed, along with practical imaging approaches.


LUNG CANCER STAGING

A number of imaging modalities have historically been used in staging lung cancer. These have included standard and conventional tomography as well as computed tomography( CT) and MRI.

In some instances, accurate staging and the determination of appropriate treatment for patients with lung cancer can be made noninvasively with imaging modalities alone, although in most cases, some degree of surgical staging and biopsy evidence is also necessary.


OVERVIEW OF STAGING Staging of any tumour is done to determine the extent

of disease. Staging information is important for 2 reasons: 1. to determine prognosis and 2. to select patients for

surgical intervention and/or a different modality. Lung cancer staging is based on criteria accepted by the American Joint Committee on Cancer. This classification system is based:• On the characteristics of the primary tumor (T),• The presence or absence of mediastinal and/or

supraclavicular lymph node (N) metastases,• And the presence or absence of distant metastatic (M)

disease


HISTORY In the old (pre 1985) lung cancer classification, stage I

and II tumours were considered amenable to surgical management, and stage III tumours were considered unresectable.

In the previous classification, tumours with limited invasion of the chest wall and mediastinum were included in the inoperable category, but under the new classification, such tumours are considered to be potentially resectable provided that vital structures in the mediastinum, such as the great vessels, heart, and aerodigestive tract, are not involved.

Stage III has been redefined and divided into stages IIIa and IIIb. Stage III b is also considered unresectable disease.


HISTORY.. T4 is now used to describe lesions with extensive

invasion of the mediastinum or diaphragm. In addition in the current system, patients with

ipsilateral nodal metastasis are also considered to have resectable cancer. However, for the most part, only patients with limited mediastinal nodal disease fall into the operable category.

N3 was added to the TNM staging to refer to contralateral mediastinal or hilar lymph node or supraclavicular LN metastases. N3 disease is considered to be nonsurgical or unresectable category.


HISTORY.. In 1997, stage I has been divided

into 2 groups: IA and IB. T4 has also been slightly redefined

to include satellite tumour nodule (s) within the ipsilateral primary lobe of the lung. Previously, any additional nodules had been considered evidence of distant metastatic disease (M1).


OVERVIEW OF STAGING Symptoms. Sputum examination. Chest radiograph CT. MRI. PET. PET CT. Bone scintigraphy. Endoscopic and endobronchial ultrasound.


SPUTUM EXAMINATION If a tumour is proven by the

presence of malignant cells in the sputum but not visualized by imaging or bronchoscopy; then it is designated as Tx.

Clinical symptoms often herald the presence of metastatic disease.


Clinical Findings Suggestive of Metastatic Disease

Test FindingSymptoms Weight loss greater than 10 lb Skeletal pain Headache, seizures, syncope Mental status change Lymphadenopathy Hoarseness Bone tenderness Hepatosplenomegaly Neurologic signs, papilledemaLaboratory Hematocrit < 40% in men or <35% in women

Elevated calcium, alkaline phosphatase, liver function tests________________________________________________________________ Data from Silvestri et al


CHEST RADIOGRAPHY The vast majority of primary lung cancers are

initially detected on routine chest radiographs. There may be certain instances in which the

chest radiograph alone is a sufficient imaging procedure for staging-for example, when an obvious metastatic bone lesion is detected or when large bulky contralateral mediastinal lymph nodes are present.

However, numerous studies have shown that the chest radiograph lacks sensitivity in detecting mediastinal LN metastases and in detecting chest wall and mediastinal invasion.


Regional lymph nodestations for staging lung cancer.


Regional lymph node stations for staging lung cancer.


Regional lymph node stations for staging lung cancer.



LUNG CANCER STAGING

The map published in 1997 was recognizedby the American Joint Committee on Cancer andthe TNM Committee of the Union InternationaleContre le Cancer .

The three groups of mediastinal LNs are indicated by a single digit:

superior (1–4), aortic (5 or 6), and inferior (7–9).Hilar (10) and intrapulmonary (11–13) LNs have a double

digit.

This map can be used to interpret imaging studies and to guide LN sampling procedures such as endoscopic needle aspirations or mediastinoscopy.


NODAL STAGE N1 nodes are ipsilateral intrapulmonary,

peribronchial, and hilar lymph nodes. N2 nodes are ipsilateral mediastinal nodes

including the midline groups, levels 3 and 7.

N3 nodes are contralateral to the primary tumour or involve the scalene or the supraclavicular lymph node regions.


N1 nodes - All N1 nodes lie distal to the mediastinal pleural reflection and within the visceral pleura


N2 nodes – All N2 nodes lie within the mediastinal pleural envelope


PATTERN OF LN SPREAD The pattern of LN spread;depends, in general, on the site of the primary tumor.Right upper- and middle-lobe tumors oftenspread to the right hilar and right superior mediastinalnodes, right lower-lobe tumors often spreadto the right hilar and inferior mediastinal stations.Left upper-lobe tumors have a predilection for lefthilar, aortic, and left paratracheal nodes; left lowerlobetumors spread to the left hilar nodes and theinferior mediastinal nodes, with a high tendencyto cross the midline.


TUMOUR SIZE T1 tumors are less than 3 cm in

greatest dimension and do not invade the visceral pleura or the main bronchi.

Whereas T2 tumours are lesions greater than 3 cm and those that involve the visceral pleura or the main bronchi at least 2 cm from the carina.


TUMOUR SIZE T3 tumors may be of any size and directly

invade the chest wall, diaphragm, mediastinal pleura, parietal pericardium, or are within 2 cm of but do not involve the carina.

T4 tumours are those that invade the heart, great vessels, esophagus, or vertebral bodies.

In general, T4 tumours can not be resected because of the involvement of vital structures.


TNM Based on their TNM denominators,

patients are grouped into stages with more-or-less homogenous prognosis. The current system distinguishes seven stages of disease, each with a different outcome.


LUNG CANCER STAGING

For therapeutic considerations, stage I and stage II disease are often referred to as `` early stage``; for these patients the standard of care is local treatment, preferably resection followed by adjuvant chemotherapy except for stage IA. or radical radiotherapy in case of poor cardiopulmonary function.


LUNG CANCER STAGING

Patients who have stage III disease, have locally advanced disease, either IIIA (N2: LN spread in the ipsilateral mediastinal nodes only) or IIIB (N3: LN spread in the contralateral mediastinal or supraclavicular nodes).


LUNG CANCER STAGING

Patients who have stage IV (advanced or metastatic) are no longer amenable to cure. Chemotherapy results in a moderate improvement of the median survival, subjective clinical benefit , or quality of life.


LUNG CANCER STAGING Table 1. Staging of NSCLC Based on TNM Classification Stage TNM 0------------------------ Carcinoma in situ 1A ------------------------- T1N0M0 1B------------------------- T2N0M0 2A--------------------------T1N1M0 2B -------------------------T2N1M0 T3N0M0 3A-------------------------T3N1M0 T1-3N2M0 3B------------------------- Any T4 Any N3 4---------------------------Any M1 Abbreviations: T, tumor; N, lymph node; M, distant metastasis




LUNG CANCER STAGE I


LUNG CANCER STAGE II


LUNG CANCER STAGE III


LUNG CANCER STAGING

The current imaging approach to lung cancer staging can be divided into 2 distinct categories: anatomic and physiologic.

Anatomic imaging is done by CT and MRI. The major limitations of the anatomic approach are the use of size criteria to define benign and malignant mediastinal lymph nodes and the nonspecific appearance of metastatic disease.


LUNG CANCER STAGING

Computed tomography (CT) remains the major tool for imaging primary lung lesions, mediastinal lymphadenopathy, and distant metastatic disease.


LUNG CANCER STAGING

CT criteria for probable resectability in masses contigous with the mediastinum are a contact with mediastinum of less than 3 cm, less than 90 contact with aorta, and preserved mediastinal fat layer between the mass and mediastinal structures.


MRI Magnetic resonance imaging (MRI) is

occasionally used to evaluate chest wall and brachial plexus involvement and image indeterminate adrenal and hepatic lesions.

MRI is the primary method of detection of cerebral metastases.


PET Positron emission tomography (PET)

overcomes some of the limitations of anatomic imaging by providing an analysis of metabolic activity.

In general, increased metabolic activity on PET indicates the presence of neoplastic tissue.


PET There are 2 methods of PET interpretation

that may be regarded as qualitative and quantitative.

Some interpret activity when compared with background mediastinal activity, whereas others calculate a standard uptake value (SUV), regarding a value over 2.0 as suspicious for malignancy.

Overall, PET has a 96.8% sensitivity and a 77.8% specificity in the detection of malignancy.


LUNG CANCER STAGING

For staging of the mediastinum, PET must be evaluated in conjunction with CT. A combined interpretive approach provides more definitive localization of the abnormality and may help to determine the appropriate diagnostic procedure.


LUNG CANCER STAGING Because PET is limited by spatial resolution, it is

critical to interpret the PET images in conjunction with a modality that depicts anatomy such as CT.

Currently, researchers favor staging lung cancer with PET CT to acquire anatomic and physiologic data in one examination.

Bone scintigraphy has been used for the detection of osseous metastases, and, ultimately, bone scans may be replaced by PET.


PET TRACERS The standard tracer in lung cancer PET imaging is the glucose analogue 18F-fluoro-2-deoxy-D-glucose (FDG). FDG allows excellent discrimination between normal tissues and tissues with enhanced glucose metabolism, But false-positive uptake of FDG in inflammatory tissues is one of its major limitations. Therefore, tracers with an equally high sensitivity but a better specificity are the focus of ongoing research. Other tracers such as 11C-methionine (a marker of protein metabolism), 11C-choline (a marker of the cell membrane component phosphaditylcholine), and 18F-fluoro-thymidine (a marker of cell proliferation) have been studied. The experience with these tracers is still limited.


FDG PET: advantages for staging themediastinum? It has been shown clearly that FDG PET is more accurate than CT for the detection of mediastinal lymph-node metastases. Dual-modality scanners might be even more exact in staging the mediastinum. However, currently only a few studies are available. In view of the high negative-predictive value of PET a patient with a negative PET scan of the mediastinum can proceed directly to thoracotomy. In contrast, a positive finding on the PET scan implies that these lymph nodes have to be examined by invasive methods (e.g. mediastinoscopy). Until now a systemic comparison between PET and FNA procedures (transbronchial or transoesophageal) have not been performed.


T1 lung cancer. Contrast-enhanced CT reveals a 2-cm nodule in the left lower lobe.


T2 lung cancer. Contrast-enhanced CT reveals a4.5-cm cavitary mass abutting the visceral pleura without invasion of the chest wall.


T3 lung cancer. Contrast-enhanced CT reveals aright upper lobe mass with invasion of the chest wall and rib destruction (arrow).


T4 lung cancer. Contrast-enhanced CT reveals aconfluent right lower lobe mass invading the mediastinum,surrounding the right inferior pulmonary vein, and growing into the interatrial septum (arrows).


Superior sulcus tumor. T1-weighted coronal gadolinium enhanced MRI reveals a left upper lobe mass extending into the supraclavicular fossa.


Solitary pulmonary nodule. (A) CT reveals a 1.5-cm ill-defined right upper lobe nodule, suspicious for malignancy. (B)Coronal FDG PET shows increased metabolic activity in the lesion. Biopsy revealed NSCLC.


False-negative PET. (A) CT reveals a 2.0-cm spiculated nodule, suspicious for malignancy. (B) FDG PET shows slightlyincreased activity (arrow) but below 2.0 SUV and the mediastinal background. The study was interpreted as negative formalignancy. The nodule was resected because of its morphologic features, and NSCLC was shown on histopathology.


Left panel: Coronal MR scan demonstrates transdiaphragmatic extension of a right lower lobe squamous cell carcinoma into the liver. This is a T4, stage IIIB tumor. Right panel: Sagittal sequence demonstrates transdiaphragmatic extension into the liver and a small pleural effusion (arrow). Courtesy of Paul Stark, MD.


N1 lymph nodes in a patient with SCLC. Contrast enhancedCT reveals two enlarged lymph nodes adjacent to the right lower lobe pulmonary artery.


N2 and N3 lymph nodes in a patient with NSCLC.Contrast-enhanced CT in a patient with a right upper lobecancer reveals enlarged level 4R (N2) and level 5 and 6 (N3) lymph nodes.


Value of PET in lymph node staging in a patient with adenocarcinoma of the lung. (A) CT shows normal sized level 4R lymph node (arrow). (B) CT shows borderline level 7 lymph node (arrow).


FDG PET reveals increased metabolic activity in multiple mediastinal lymph nodes


Value of endoscopic ultrasound in mediastinal staging.(A) Contrast-enhanced CT reveals a left lower lobe tumor (T) associated with a mildly enlarged level 8 lymph node.


FDG PET shows increased activity in the primary tumor (T) but

not in the mediastinal lymph nodes


Endoscopic ultrasoundreveals a small level 8 lymph node (arrow). FNAB confirmed NSCLC. (LA, left atrium; A, aorta).


ENDOSCOPIC ULTRASOUND Endoscopic ultrasound with FNAB is a

minimally invasive technique to image and sample lymph nodes in the mediastinum.

Using the esophagus as a window, endoscopic ultrasound is able to directly visualize lymph nodes at levels 4L, 5, selected 6, 7, and 8.

Right-sided nodes are often not visualized because of air within the trachea.


ENDOSCOPIC ULTRASOUND By sonographic characteristics alone,

sensitivity (78%) and specificity(71%) are modest.

Endoscopic ultrasound-guided FNAB increases the specificity to almost 100%.

Endoscopic ultrasound with FNAB is best for evaluating enlarged lymph nodes, and it may yield positive results in up to one third of patients with negative mediastinal lymph nodes on CT.


Value of PET in detecting occult metastatic disease. (A) FDG PET performed to evaluate a left upper lobe solitarypulmonary nodule (arrowhead) reveals an unsuspected region of increased uptake in the right chest wall (arrows).


T1-weightedaxial gadolinium-enhanced MRI reveals an enhancing mass between the right fifth and sixth ribs. Biopsy confirmed metastatic adenocarcinoma.


Value of PET in detecting bone metastases.

Technetium 99m medronate scintigraphy interpreted as normal in a patient with left upper lobe mass. In retrospect,there is minimally increased activity in the region of the leftlesser trochanter (arrow).


Value of PET in detecting bone metastases.

Coronal FDG PET clearly shows increased metabolicactivity in the region of theleft lesser trochanter (arrow).CT and subsequent biopsyrevealed cortical metastases.


SMALL CELL LUNG CANCER SCLC accounts for about 14% of all

new cases of lung cancer. It is more aggressive than the non-

small cell form, with median survival of 2-4 months if untreated.

The system of staging SCLC is a two-stage system based on studies of the Veterans Administration Lung Study Group.


SCLC STAGING In this system, patients are classified as

having either limited or extensive disease. Limited disease: the tumour is confined to

one hemithorax and to the regional LNs. Extensive disease: tumour is beyond this

area in contralateral lung or extrathoracic sites; 60-80% of newly diagnosed SCLC.


SMALL CELL LUNG CANCER

Posterior-anterior chest radiograph reveals a mass in the aortopulmonary window.


SMALL CELL LUNG CANCER

Contrast-enhanced CT reveals a large mass invading the mediastinum, surrounding the left main bronchus (B), and attenuating the left pulmonary artery.


SCLC with superior vena cava syndrome. (A) Contrast-enhanced CT reveals mediastinal lymphadenopathy obstructing the superior vena cava. (B) At the level of the thoracic inlet, bilateral internal jugular venous thrombosis (*) is present


Value of PET in the detection of extensive stage SCLC

Unenhanced CT reveals enlarged lymph nodes surroundingthe left upper lobe bronchus (arrows)


SMALL CELL LUNG CANCER..

Level 6 lymphadenopathy (arrows)


FDG PET reveals increased uptake in the leftpedicle and the left facet joint of the L4 vertebra (arrows), unsuspected by physical exam or by bone scintigraphy.


Coronal T1-weighted MRI reveals low-signal intensity (arrow). Biopsy confirmed metastatic SCLC.


Endobronchial ultrasonography bronchoscopewith a curved linear array ultrasound transducerallowing real-time fine-needle aspiration.618 Wynants et al


METASTATIC DISEASE Metastases (M) status may be either M0 (no distant

metastasis) or M1 (distant metastasis). Clinical symptoms often herald the presence of

metastatic disease and the absence of symptoms results in a negative predictive value of 95% for liver, adrenal, and brain metastases and 90% for bone metastases.

CT and whole-body PET are often used to assess for occult metastatic disease.

Other imaging modalities include radionuclide bone scan for detecting skeletal metastases and MRI for identifying adrenal, liver, and brain metastases.


Chest radiograph shows a solitary pulmonary nodule in the right lower lobe, measuring less than 3 cm in diameter (arrow). This was a stage IA, T1N0M0 bronchogenic carcinoma. Courtesy of Paul Stark, MD.


CT scan of a stage IB, T2N0M0 bronchoalveolar cell carcinoma demonstrates a right lower lobe mass, measuring 3.5 cm in diameter with a so-called rabbit ear sign and with central lucencies that probably represent air bronchograms rather than cavitation. Courtesy of Paul Stark, MD.


CT scan of a stage IIB, T2N1M0 bronchogenic carcinoma shows a mass in lingula, measuring 5 cm in diameter (large arrow), with dystrophic calcification and hilar lymph node enlargement (small arrow). A small left pleural effusion proved to be benign, and therefore did not affect staging of the tumor. Courtesy of Paul Stark, MD.


T2 lesion seen on chest radiograph in the left lung. Patient presents with joint pain and hypertrophic osteoarthropathy. Courtesy of Paul Stark, MD.

Primary mucinous adenocarcinoma


Squamous cell carcinoma of the left upper lobe bronchus leading to left upper lobe atelectasis. Oblique linear tomogram shows the tumor to be more than 2 cm from the carina. This is still a T2 tumor. Courtesy of Paul Stark, MD.


Squamous cell carcinoma of the left upper lobe bronchus leading to left upper lobe atelectasis. Oblique linear tomogram shows the tumor to be more than 2 cm from the carina. This is still a T2 tumor. Courtesy of Paul Stark, MD.


CT scan shows peripheral mass, in the right lung representing a T3 bronchogenic carcinoma, invading and extending through the intercostal space. Courtesy of Paul Stark, MD.


Peripheral bronchogenic carcinoma in left upper lobe, invading the chest wall (arrow). CT shows infiltration of the left pectoralis muscle and tumor extension into the deep axillary subcutaneous fat. The findings are consistent with a T3 lesion. Courtesy of Paul Stark, MD.


Coronal, axial, and sagittal MR sequences in a superior sulcus tumor (arrows). Left panel: Coronary sequence shows large peripheral right upper lobe mass invading the superior chest wall and extending into the base of the neck. The vertebral body and the spinal canal are not involved. Middle panel: Axial sequence also shows the mass invading the superior chest wall and extending into the base of the neck. Right panel: Sagittal sequence of the mass shows that right subclavian vein and artery are patent and a pleural effusion is apparent (small arrow). The malignant effusion changes the classification from T3 to T4. Courtesy of Paul Stark, MD.


CT scan in a patient with bronchogenic carcinoma shows a central mass encasing the right mainstem bronchus (large arrow), in close proximity to the carina. There are also speckled calcifications in the hilar mass and in subcarinal nodes (small arrow) from previous granulomatous disease. The location of this hilar mass is consistent with a T3 tumor. Courtesy of Paul Stark, MD.


Squamous cell carcinoma of the left mainstem bronchus with almost total atelectasis of the left lung, producing opacification of the left hemithorax. The trachea is deviated to the left. These findings indicate a T3 tumor. Courtesy of Paul Stark, MD.


CT scan shows a large mediastinal mass in close proximity to the ascending aorta (Ao), invading the precarinal, retroaortic space. There is also marked narrowing of the superior vena cava. This is radiologically a T4, stage IIIB tumor. Courtesy of Paul Stark, MD.


CT scan shows a large tumor encasing the mainstem bronchi and the ascending aorta (Ao). A small right paravertebral mass is also seen (small arrow). This is radiologically a T4, stage IIIB tumor. Courtesy of Paul Stark, MD.


Chest frontal radiograph shows right lower lobe atelectasis (arrow) with accompanying right pleural effusion due to a bronchogenic carcinoma. Courtesy of Paul Stark, MD.


Left panel: CT scan of an advanced bronchogenic carcinoma shows right lower lobe atelectasis with accompanying right pleural effusion. Right panel: Barium esophagram from this patient demonstrates an esophagopulmonary fistula (arrow) that indicates mediastinal extension and invasion by this T4, stage IIIB tumor. Courtesy of Paul Stark, MD.


Left panel: Chest radiograph shows diffuse left sided mediastinal widening (arrow). Right panel: A barium esophagram reveals a fistula between the left mainstem bronchus and the esophagus. This is a T4, stage IIIB bronchogenic carcinoma. Courtesy of Paul Stark, MD.


Poorly differentiated adenocarcinoma of the lung with extensive mediastinal invasion and bronchoesophageal fistula. A stent was inserted into the esophagus as a palliative measure. Courtesy of Paul Stark, MD.


PET scan with FDG shows a right upper lobe solitary pulmonary nodule in cross-sectional (A), sagittal (B), coronal (C) views. This was a stage IA, T1N0M0 bronchogenic carcinoma. Courtesy of Paul Stark, MD.


Stage 1, T1N0M0 peripheral bronchogenic carcinoma in left upper lobe. FDG PET scan shows a small peripheral left upper lobe nodule in cross-sectional display. Courtesy of Paul Stark, MD.


CT scan shows bilateral calcified hilar lymph nodes, station 10 by the 1997 classification (arrows). When enlarged due to an ipsilateral bronchogenic carcinoma, they represent N1 nodes. Courtesy of Paul Stark, MD.


CT scan in a patient with bronchogenic carcinoma and right hilar lymph node enlargement (arrow). This represents nodal station 10 involvement by the 1997 classification (N1 disease). Courtesy of Paul Stark, MD.


CT scan shows right high paratracheal lymph node (arrow), group 2R. This indicates an N2, stage IIIA tumor, provided the primary cancer is on the ipsilateral side. Courtesy of Paul Stark, MD.


CT scan shows left (left panel) and right (right panel) supraclavicular node enlargement (N) in patients with bronchogenic carcinoma. Spread to the supraclavicular lymph nodes indicates N3 involvement. Courtesy of Paul Stark, MD.


CT scan from a patient with left upper lobe poorly differentiated adenocarcinoma invading the mediastinum. Left panel: Left lower (large arrow) and right lower (small arrow) paratracheal lymph node involvement, stations 4R and 4L. Right panel: More caudal view shows tumor encasing the left pulmonary artery (arrow) and the descending aorta (Ao). Enlarged subcarinal lymph nodes are present, station 7. The tumor is stage IIIB, unresectable on account of the T4 disease and the N3 contralateral lymph nodes. Courtesy of Paul Stark, MD.


CT scan shows extensive mediastinal lymph node involvement in lung cancer. Enlarged prevascular lymph nodes, station 3, indicating a stage IIIB unresectable tumor. Courtesy of Paul Stark, MD.


Peripheral left upper lobe bronchogenic carcinoma with amorphous central calcification and with aortopulmonary window (station 5, long arrow) and contralateral pretracheal, retrocaval lymph nodes (station 4R, short arrow), probable stage IIIB. Courtesy of Paul Stark, MD.


CT scan shows slightly enlarged lymph nodes located anterior to the tracheal bifurcation (arrow). Courtesy of Paul Stark, MD.


Left panel: Bronchogenic carcinoma with a right-sided drowned lung. CT scan of the lower chest shows a large, opacified right lung with mucoid bronchograms appearing as low attenuation branching structures. Right panel: Upper abdominal CT scan shows several large low attenuation metastases in the liver. This is a T4, M1, stage IV tumor. Courtesy of Paul Stark, MD.


CT scan of the upper abdomen shows a large low attenuation necrotic left adrenal metastasis (small arrow) and another low attenuation necrotic metastatic focus in the pancreas (large arrow). This is a stage IV lung cancer because there is metastatic (M1) disease. Courtesy of Paul Stark, MD.


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Lung cancer staging the noninvasive tools