Lung cancer staging

1. Lung cancer staging DR. KOMALDEEP JUNIOR RESIDENT PULMONARY MED TBHP

2. Causes and Risk factors of Lung Cancer

3. diagnosis

4. 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.

5. 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.

6. CLINICAL STAGING Pre-treatment PATHOLOGICAL Post-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

8. Staging and grading stage 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.

9. 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.

10. History of staging of sclc According 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.

11. 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.”

13. 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

14. 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

15. 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

16. T4 tumor Tumour 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

17. Regional lymph nodes (N)

18. 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

19. n2 • Metastasis in ipsilateral mediastinal and/or subcarinal lymph nodes • N2 means at least stage IIIa

20. 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. 

21. Distant metastasis

22. m1 • M1a : Separate tumour nodules in a contralateral lobe Or • Tumour with pleural nodules or malignant pleural effusion. • M1b: Distant metastasis in extrathoracic organs

23. Special situations

24. GENERAL RULES: • All cases should be confirmed microscopically. • Two classifications are described for each site: Clinicalclassification AND Pathologicalclassification • 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.

25. 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 anatomicstage/prognosticgroups , 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.

26.  stage grouping : "shorthand notation"

27. 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”

28. 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

29. 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

30. 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

31. 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.

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

33. 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.

34. 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

35. 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

36. 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)

38. CHESTRADIOGRAPHY • 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.

39. 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.

40. 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

41. 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.

42. 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

43. 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)

44. Group A: extensive mediastinal infiltration by the primary tumor. GroupB: 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 .

45. 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.

46. Video assisted thoracic surgery • Better staging regarding the T descriptor, givenwe 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.

47. 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.

48. 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.

49. 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.

50. 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.