DR. KOMALDEEPJUNIOR RESIDENTPULMONARY MED

TBHP

Causes and Risk factors of Lung Cancer

diagnosis

Definition of Clinical Stage The extent of disease that can be determined from

history and physical examination, biopsy procedure, imaging studies, endoscopy, and exploration prior to initial treatment.

Importance : Why do we need Clinical Staging?

To aid the clinician in the planning of treatment. To give some indication of prognosis. To assist in evaluation of the results of treatment. To facilitate the exchange of information between treatment

centres. To contribute to the continuing investigation of human cancer.

CLINICAL STAGINGPre-treatment

PATHOLOGICALPost-treatment

• based on findings gathered by the doctor by non-invasive or minimally invasive techniques like physical exam, radiological exam, endoscopic ultrasound, bronchoscopy, mediastinoscopy and thoracoscopy.

• used to plan the initial therapy

• may be modified by additional information found during pathological examination

• Based on the examination of the tissue samples obtained from the primary tumor, nodes or metastasis

• Helpful in planning additional treatment and follow-up

CLASSIFICATION DATA SOURCE

Clinical (pretreatment)(cTNM)

symptoms, physical examination, imaging,endoscopy; biopsy; surgical exploration without resection etc

Pathologic (pTNM)

surgical resection and pathology

Post therapy (ycTNM or ypTNM)

after systemic or radiation beforesurgery or as primary therapy denoted with a yc (clinical)or yp (pathologic)

Retreatment (rTNM)

at time of retreatment for recurrenceor progression

Autopsy (aTNM)

as determined at autopsy

Staging and gradingstage grade Cancer stage refers to the size and/or

extent (reach) of the original (primary) tumor and whether or not cancer cells have spread in the body.

Tumor grade is the description of a tumor based on how abnormal the tumor cells and the tumor tissue look under a microscope. It is an indicator of how quickly a tumor is likely to

grow and spread.

Dr. Pierre Denoix, a surgical oncologist (Institut Gustave-Roussy in Paris) analyzed a series of papers published between 1943 and 1952.

Published by the International Union Against Cancer (UICC) in 1968

The second “international” recommendation came in 1974 with the support of the American Joint Committee on Cancer (AJCC).

6th edition in 1997; 5,319 cases;USA, published in 2002.

7the edition; 100,869 patients; 46 sources in 19 countries-, 81,015 were eligible for inclusion.

7th edition took effect on january 1st , 2010.

1 1977

1978–1983

2 1983

1984–1988

3 1988

1989–1992

4 1992

1993–1997

5 1997

1998–2002

6 2002

2003–2009

7 20o9

2010-

History of staging of sclcAccording to veterans administration lung study group: 2 stages of SCLC. Limited stage disease LD SCLC: Confined to the hemithorax of origin, the

mediastinum, or the supraclavicular nodes.

Extensive stage disease ED-SCLC: Any disease not meeting limited stage criteria and with Distant metastasis

The international association for the study of lung cancer (IASLC) revised the VALG classification in accordance with the TNM system.

LD definition is consistent with stages I to IIIb ED is limited to patients with distant metastasis.

TNM Staging system for Lung Cancer

T= Tumor : size or contiguous extension of the primary tumor

N= Node : the absence, or presence and extent of cancer in the regional draining lymph nodes.

M= Metastasis : the absence or presence of distant spread or metastases involvement in organs and tissues

“We’re all in the same game; just different levels,

Dealing with the same hell; just different devils.”

Descriptor Definition subgroups

T0 No evidence of primary tumour

T1 Tumour <3cm, in the greatest dimension surrounded by lung or visceral pleura, not proximal than the lobar bronchusTumour </= 2cm in greatest dimensionTumour >2cm but </=3cm in the greatest dimension

T1aT1b

T2 Tumor >3cm but <7cm orTumor with any of the following features: Involves main bronchus >2cm distal to carinaInvades visceral pleuraAssociated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung.T2a : >3 but <5cmT2b: >5 but <7cm

T2aT2b

T3 Tumour >7cm or directly invading chest wall, diaphragm, phrenic nerve, mediastinal pleura or patietal pericardiumTumour in the main bronchus <2cm distal to carinaAtelectasis/obstructive pneumonitis of the entire lungSeparate tumour nodules in the same lobe

T4 Tumour of any size with invasion of heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral bodyOr carinaOr separate tumour nodules in a different ipsilateral lobe

T1 tumor Tumor <3cm diameter

Surrounded by lung or visceral pleura

Without invasion of more proximal than lobar bronchus.

T1a: <2cm

T1b: >2cm but <3cm

T2 Tumor Tumor >3cm but <7cm or

Tumor with any of the following features:

Involves main bronchus >2cm distal to carina

Invades visceral pleura

Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung.

T2a : >3 but <5cm

T2b: >5 but <7cm

T3 tumor Tumour >7cm with :

directly invading chest wall, diaphragm, phrenic

nerve, mediastinal pleura or patietal pericardium

Tumour in the main bronchus <2cm distal to carina without involvement of carina.

Atelectasis/obstructive pneumonitis of the entire lung

Separate tumour nodules in the same lobe

T4 tumorTumour of any size with invasion of : Heart, great vessels, trachea, recurrent laryngeal

nerve, esophagus, vertebral body

Or carina

Or separate tumour nodules in a different ipsilateral lobe

Regional lymph nodes (N)descriptor definition

N0 No regional lymph node metastasis

N1 Metastasis in ipsilateral peribronchial and/or perihilar lymph nodes and intrapulmonary nodes, including involvement by direct extension

N2 Metastasis in ipsilateral mediastinal and/or subcarinal lymph nodes

N3 Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph nodes

N0 & n1 Metastasis in ipsilateral peribronchial and/or

perihilar lymph nodes and intrapulmonary nodes, including involvement by direct extension

N1 means at least stage IIa

n2 Metastasis in ipsilateral mediastinal

and/or subcarinal lymph nodes

N2 means at least stage IIIa

n3 Metastasis in contralateral mediastinal,

contralateral hilar, ipsilateral or contralateral scalene or supraclavicular lymph nodes

N3 means at least stage IIIb

N3-nodes are clearly unresectable. 

Distant metastasisdescriptor definition subgroups

M0 No distant metastasis

M1a

M1b

Separate tumour nodules in a contralateral lobe or tumour with pleural nodules or malignant pleural effusion

Distant metastasis in extrathoracic organs

M1a contr nod

M1a pl dissem

M1b

m1 M1a : Separate tumour nodules in a contralateral

lobe

Or

Tumour with pleural nodules or malignant pleural effusion.

M1b: Distant metastasis in extrathoracic organs

Special situationsdescriptor definition subgroups

Tx, Nx, Mx T, N or M status cannot be assessed

Tis Focus of in situ cancer Tis

T1 Superficial spreading of tumour of any size but confined to the wall of the trachea or main stem bronchus

T1ss

GENERAL RULES: All cases should be confirmed microscopically. Two classifications are described for each site: Clinical classification AND

Pathological classification After assigning T, N and M and/or pT, pN and pM categories, these may be grouped

into stages. The TNM classification and stage grouping, once established, must remain

unchanged in the medical records. If there is doubt concerning the correct T, N or M category to which a particular

case should be allotted, then the lower (i.e., less advanced) category should be chosen.

In the case of multiple simultaneous tumours in one organ, the tumour with the highest T category should be classified and the multiplicity or the number of tumours should be indicated in parentheses.

TNM Groupings A tumour with four degrees of T, three degrees of N, and two degrees of M will

have 24 TNM categories T, N, and M are grouped into so-called anatomic stage/prognostic groups ,

commonly referred to as stage groups. Groups are classified by Roman numerals from I to IV with increasing severity of

disease. Stage I generally denotes cancers that are smaller or less deeply invasive with

negative nodes Stage II and III define cases with increasing tumor or nodal extent Stage IV identifies those who present with distant metastases (M1) at diagnosis.

In addition, the term Stage 0 is used to denote carcinoma in situ with no metastatic potential. Stage 0 is almost always determined by pathologic examination.

 stage grouping : "shorthand notation"

Stage I Non-Small Cell Lung Cancer

Cancer is found only in the lung

Surgical removal recommended

Radiation therapy and/or chemotherapy may also

be used

“If you don’t look at the lymph nodes, everyone has stage 1 disease”

Stage II Non-Small Cell Lung Cancer The cancer has spread to lymph nodes in the lung

Treatment is surgery to remove the tumor and nearby lymph nodes

Chemotherapy recommended; radiation therapy sometimes given after chemotherapy

Stage III Non-Small Cell Lung Cancer

The cancer has spread to the lymph nodes located in the center of the chest, outside the lung

Stage IIIA cancer has spread to lymph nodes in the chest, on the same side where the cancer originated

Stage IIIB cancer has spread to lymph nodes on the opposite side of the chest, under the collarbone, or the pleura (lining of the chest cavity)

Surgery or radiation therapy with chemotherapy recommended for stage IIIA

Chemotherapy and sometimes radiation therapy recommended for stage IIIB

Stage IV Non-Small Cell Lung Cancer

The cancer has spread to different lobes of the lung or to other organs, such as the brain, bones, and liver

Stage IV non-small cell lung cancer is

treated with chemotherapy

Limitations of new classification

No data at all being included from Africa, South America or the Indian subcontinent.

Russia, China, and Indonesia are not represented or only poorly represented.

The database used for the 7th edition predates the widespread and routine use of PET which has had an enormous impact on clinical staging algorithms.

Lympahngitis carcinomatosis is believed to be associated with worse prognosis in lung cancer patients. However, there is no evidence to support this. The new TNM classification does not specifically take account of lymphangitis.

OTHER CLASSIFICATIONAnn Arbour lymphomasDuke’s classification colon cancer Breslow scale and Clark’s level melanoma

MEDIASTINAL STAGING Determining the involvement of the mediastinal lymph nodes.

Mediastinal lymph nodes status and the presence or absence of direct tumor mediastinal invasion will determine the eligibility of the patient to treatment with intention to cure (surgical treatment) or a palliative care intending to prolong life and better quality of life.

A Brief History Naruke et al proposed the 1st lymph node map in the 1960s

The Next 30 years: Mountain system proposed in 1973(2,155 patients) : The Mountain Era

Revised in 1997(5,319 patients)

The IASLC Staging System: Performed by the International Association for the Study of Lung Cancer

IASLC lymph node map 2009

Supraclavicular nodes 1 

Superior Mediastinal Nodes 2-4 2r 2l right and left upper paratracheal 3a 3p : prevascular and prevertebral 4r 4l: right and left lower paratracheal

Aortic Nodes 5-6 5: subaortic 6: paraaortic

Inferior Mediastinal Nodes 7-9 7: subcarinal 8: paraesophageal 9: pulmonary ligament

Hilar, Lobar and (sub)segmental Nodes 10-14 10: hilar 11: interlobar 12: lobar 13: segmental 14: subsegmental

American Thoracic Society mapping scheme.

Supraclavicular zone (1)

Superior Mediastinal Nodes (2-4) 2. Upper Paratracheal 3A. Pre-vascular 3P. Pre-vertebral 4. Lower Paratracheal 

Aortic Nodes (5-6) 5. Subaortic 6. Para-aortic

Inferior Mediastinal Nodes (7-9) 7. Subcarinal. 8. Paraesophageal (below carina). 9. Pulmonary Ligament

Hilar, Interlobar, Lobar, Segmental and Subsegmental Nodes (10-14)

Non- invasive invasive

Chest radiography Mediastinoscopy : GOLD STANDARD

Computed tomography Video Assisted Thoracic Surgery

PET scan Anterior Mediastinotomy (Chamberlain procedure;

MRI Endobronchial Ultrasound with Fine Needle Aspiration (EBUS-FNA)

Endoscopic Ultrasound with Fine Needle Aspiration(EUS-FNA)

Transbronchial Fine Needle Aspiration (TBNA-FNA)

In certain situations, the plain film may be sufficient to detect spread

to the mediastinum. For example, the presence of bulky lymphadenopathy in the superior

or contralateral mediastinal areas may be considered adequate evidence of metastatic disease.

Can detect pleural effusions that obliterate costophrenic recesses and lung nodules larger than 7 mm.

Every patient suspected of having lung neoplasm must have a posterior-anterior and lateral chest radiograph

Still, most patients should undergo CT scan of the chest unless they are so debilitated that no further evaluation or treatment is planned.

CHEST RADIOGRAPHY

COMPUTED TOMOGRAPHY OF THE CHEST

The lung lesion itself is more specifically evaluated by CT

scan, characteristics of the primary mass (i.e., smooth bordered, spiculated, calcified, etc.), the limits of the lesion are better assessed and the rest of lung parenchyma may be screened for additional lesions.

Routine chest CT may also evaluate the presence of distant metastasis to the liver, adrenals or bones, which are some of the commonest sites of metastatic disease.

The bony structures of the thoracic cavity can also be evaluated by chest CT.

POSITRON EMISSION TOMOGRAPHY

This imaging modality is based on the biologic activity of neoplastic cells.

PET is better used in conjunction to CT (PET-CT) in which single machine incorporates CT and PET during the same scan.

LIMITATIONS : Brain metastasis Inflammation: TB, fungal etc. Slow growing neoplasms: BAC,

carcinoid tumour Size smaller than 7mm

MRI There are very few circumstances in which

magnetic resonance imaging (MRI) is a useful tool in staging lung cancer.

Helps in evaluating limits and possible invasion in soft tissue, bone and vascular structures but, with new generations of multislice CT scans that are capable to perform three-dimensional angiotomography, MRI has diminished one of its main indications, which is to evaluate vascular and neural invasion in superior sulcus tumor.

Its main use is to image the brain when suspecting of metastasis at this organ.

THE SEARCH FOR METASTATIC DISEASE

To detect metastatic disease at common metastatic sites, such as the adrenal glands, liver, brain, and skeletal system, thereby sparing the patient fruitless surgical intervention.

Computed tomography of the chest, CT or MRI with contrast of the brain, and 99mTc nuclear imaging of the skeletal system, whole-body PET scans for extrathoracic staging.

False-positive scans- Adrenal adenomas (present in 2% to 9% of the general population), hepatic cysts, degenerative joint disease, old fractures, and a variety of nonmetastatic space-occupying brain lesions are present in the general population.

False-negative scans—that is, metastases are present but not picked up by current scanning techniques

Invasive Mediastinal Staging of Lung Cancer After distant metastasis has been ruled out, the mediastinal staging is the most

important aspect to focus in these patients. The main purpose of the IMS is to differentiate:

a) patients that will benefit from straight surgical resection

b) patients that will benefit from neoadjuvant therapy, followed by surgical resection;

c) patients who will not benefit from surgical resection, and should receive only chemo and/or radiotherapy.

In general, patients with lung cancer may be divided in four categories, according to tomographic characteristics of the primary tumor and the mediastinum, regarding to size, location and extension of the disease

(proposed by Dr. Frank Detterbeck and adopted by the American College of Chest Physicians Guidelines for Diagnosis and Management of Lung Cancer)

Group A: extensive mediastinal infiltration by the primary tumor.

Group B: enlarged paratracheal lymph nodes.

Group C: central tumor with normal-sized mediastinal lymph nodes.

Group D: peripheral small tumor with normal-sized mediastinal lymph nodes .

Mediastinoscopy The procedure is done through a transverse

cervical incision, with pretracheal dissection until the mediastinum and introduction of the mediastinoscope.

It is possible to perform biopsies of the following lymph nodes:

Pretracheal(1), Right and left high and low paratracheal (3,2R, 2L, 4R, 4L),Subcarinal(7)

The procedure may also be done with the videomediastinoscope, allowing a magnification of the operative field.

Mediastinoscopy is the gold standard method to the invasive mediastinal staging, with which the other methods should be compared.

Video assisted thoracic surgery Better staging regarding the T descriptor, given we

have the wide approach to the pleural cavity, making possible a better evaluation of pleural effusion, pleural metastatic disease, chest wall, diaphragm and vascular structures invasion.

At the right side, paratracheal lymph nodes are relatively easily accessed, but left paratracheal lymph nodes are extremely difficult to be accessed by this method, due to the great vessel’s anatomy.

VATS not a substitution but is a complementary procedure to the mediastinoscopy, especially when there is a left upper lobe tumor with enlarged lymph node station 5 and 6.

Allows simultaneous resection of the tumour. Limitation: unilateral approach.

Anterior mediastinotomy (chamberlain procedure)

A horizontal incision is done through second left intercostal space, and the aortic arch and left pulmonary artery are identified by palpation.

Regarding to lung cancer staging, anterior mediastinotomy is used exclusively in selected patients with left upper lobe (LUL) tumor, aiming to evaluate lymph nodes at the aortopulmonary window (station 5) and preaortic (station 6).

When there is cancer spread only to these stations, usually patients have a better prognosis and, if patients are fit, there are two possible treatements: 1) neoadjuvant therapy aiming to posterior pulmonary resection intending to cure; 2)surgical resection followed by adjuvant chemotherapy.

Endobronchial ultrasound with fine needle aspiration

Accessible lymph nodes by this method are pretracheal (1), high and down right and left paratracheal (2R, 2L, 4R. 4L), and subcarinal(7).

It may be used in substitution to mediastinoscopy, but, if the results are negative with the EBUS, the mediastinoscopy should be performed.

There are many false negatives with EBUS, thus, if a high index of suspicion exists, a mediastinoscopy should be performed when EBUS was negative.

Doppler feature allows for identification of vessels and landmarks for nodal stations.

Endoscopic ultrasound with fine needleaspiration (EUSFNA)

EUS is performed using an ultrasound transducer coupled with the flexible esophagoscope.

This device guides the needle through the esophageal wall and allows the approach of lymph nodes in pulmonary ligament(9), paraesophageal(8), subcarinal(7) and aortopulmonary window(5).

Additionally, EUS may be able to detect metastatic disease in sites as left adrenal gland, celiac lymph nodes and liver and also direct invasion to some mediastinal structures (T4).

The ideal procedure is when both (EUS & EBUS) methods are performed at the same session, with the patient under general anesthesia or sedation.

Transbronchial needle aspiration (TBNA)

TBNA utilizes a standard flexible bronchoscope and a needle, known as Wang Needle through the scope.

Its main indication is to evaluate enlarged subcarinal lymph nodes (station 7).

Negativity of this test should prompt the mediastinal evaluation by other method, such as mediastinoscopy.

Operator dependent.

TBNA is safe and performed in an outpatient basis.

Thoracocentesis Aspiration and cytological examination of pleural fluid in

patients presenting with suspected malignant pleural effusion

provides a diagnostic yield of approximately 60%;

the addition of needle pleural biopsy may raise the possibility

of detecting cancer to 75%.

The presence of neoplastic cells in the fluid excludes surgical treatment.

Will be of help only if there is pleural involvement by the tumor.

When there is no diagnosis of pleural fluid after thoracocentesis and the effusion is recurrent, one should perform a videothoracoscopy, which have a sensibility of 95% in detecting pleural metastasis (by pleural biopsy and fluid analysis), and also has the advantage of allowing to perform the pleurodesis at the same surgical procedure.

TTNA Transthoracic needle aspiration, usually under CT

or fluoroscopic guidance, is an expedient and relatively safe way to diagnose the primary tumor mass and establish a diagnosis of lung cancer.

As a general rule, if a lesion is less than 3 cm in size and lateral to the mid-clavicular line, bronchoscopy would not be the diagnostic procedure of choice. Transthoracic needle aspiration should be considered under such circumstances if tissue diagnosis is necessary.

Special Situations1.Left upper lobe tumors Patients with left upper lobe (LUL) tumors deserve a special mention,

because the lymphatic system drains preferentially to lymph nodes in the aortopulmonary window (station 5) and preaortic location (station 6).

These nodes are rarely involved by tumors originating from other pulmonary lobes.

The approach to station 5 and 6 must be done by anterior mediastinoscopy or videothoracoscopy, and choosing between these two methods must be individualized according to each patient

2.Pancoast tumor A Pancoast tumor is a tumor of the superior pulmonary sulcus

characterized by pain due to invasion of the brachial plexus,

Horner's syndrome and destruction of bone due to chest wall invasion. Pancoast tumors are staged at least as T3, because there is almost

always chest wall invasion.  When there is ingrowth into a vertebral body or vital mediastinal

structures, the tumor is staged as T4. Ipsilateral supraclavicular nodes (N3) (peritumoral lymph nodes)

are potentially resectable with en bloc resection, while mediastinal nodes (N2) are not.

After histological diagnosis, if noninvasive staging points to the possibility of a pulmonary resection, the mediastinum must obligatory be invasive staged.

3.Invasive re-staging after neoadjuvant treatment

If previous IMS was positive, it is obligatory to repeat it, more commonly with the mediastinoscopy;

If previous IMS was negative and the new CT and PET-CT show neither enlargement nor augmentation in the SUV when compared to the CT and PET-CT performed before the neoadjuvant therapy, it is not necessary to repeat the IMS;

If previous IMS was negative, but the new CT and PETCT reveal mediastinal node enlargement and/or augmentation in SUV comparing to the CT and PET-CT performed before the neoadjuvant therapy, the IMS must be performed again, usually by mediastinoscopy.

Finally, after neoadjuvant therapy, if N2 or N3 disease is detected in this second IMS, the patient will not benefit from surgical resection; if there is no N2 or N3 disease, the patient should have a pulmonary resection.

Conclusion : Staging matters!!! Lung cancer staging must have a simple and logical sequence.

The only possible method to cure this neoplasm is by surgical resection, therefore a correct staging should be offered to every patient facing this disease.

The most important point when evaluating a patient suspected of having lung cancer, refers to the oncological status of mediastinal lymph nodes, and its evaluation, by means of radiological examinations or invasive procedures, is the critical part for every patient.

Every patient should start the investigation with a chest radiograph and chest CT with intravenous contrast.

The clinician must be wary of abnormal scans that may falsely suggest metastatic disease to the mediastinum and distant sites

Conclusion : Staging matters!!! After this initial evaluation, the mediastinal evaluation should be complemented

based on the size of mediastinal lymph nodes, the location and size of the lung lesion. Recently, PET-CT has been added to the investigation of every patient who is a potential candidate for pulmonary surgical resection.

Tissue confirmation by whatever means necessary is the rule rather than the exception prior to deciding on correct stage and the most appropriate treatment.

A detailed preoperative workup is essential to choose the most appropriate therapeutic plan to each patient, with best results regarding to possible cure, improvement of quality of life, rational use of medical resources and less morbidity and mortality.