1. Diagnostic procedures, Staging and Surgery of Lung Cancer Balkan Masterclass in Clinical Oncology 11-15 May 2011 Dubrovnik, Croatia Dragana Jovanovic Clinical Hospital of Pulmonology Clinical Centre of Serbia Belgrade

2. Symptoms and signs of lung cancer Recognising the symptoms and signs of lung cancer is an important first step in establishing the diagnosis Provides information on disease stage and prognosis. By the time lung cancer causes symptoms and signs, the patient often has advanced disease that is beyond cure. When they do occur, are often nonspecific, causing further delay in diagnosis

3. Symptoms and signs of lung cancer 1) growth of the primary tumour 2) intrathoracic metastasis of the tumour 3) extrathoracic metastasis 4) paraneoplastic syndromes 5) constitutional effects of cancer Most frequent: - Cough ± hemoptysis - Different degree of dyspnoea - Pain of different intensity - Loss of appetite and body weight loss - Fatigue

5. Haemoptysis in up to 35% of patients

6. Recurrent or unresolved pneumonia

7. Dyspnoea in up to 60% of patients , wheeze and stridor

8. Chest painLocalization of lung cancer central peripheral Atelectasis of right lung Atelectasis of left upper lobe

9. Symptoms and signs of intrathoracic metastasis Superior vena cava obstruction Pancoast’stumour and Horner’s syndrome Recurrent laryngeal nerve palsy Phrenic nerve palsy Dysphagia Cardiac involvement Chest wall invasion Pleural disease

10. Symptoms and signs of intrathoracic metastasis Superior vena caval obstruction SVCSis due to the compression or invasion of vena cava with tumor mass and intraluminal thrombus, presents with oedema and plethora of the face, dilated veins on the neck, upper torso and arms, with headache and cerebral oedema. SVCS is a poor prognostic factor.

13. Horner’s Sy: involvement of the sympathetic chain tumour causing unilateral enophthalmos, ptosis, miosis and anhydrosis of the face.

14. Symptoms and signs of extrathoracic metastasis Supraclavicular lymph nodes Liver · Brain and Spinal cord · Bone Skin Coeliac lymph nodes… Adrenal glands Symptoms and signs that predict extrathoracic metastasis ACCP 2007

16. Endocrine – Cushing Sy, SIADH…

17. Cutaneous

18. Connective tissue

22. chest X ray

23. CT scan , MRI, PET-CT

24. ultrasound of the abdomen

26. Thoracotomy Histological or cytological specimens can be obtained from the primary tumor, lymph node or distant metastases or malignant effusions. The least invasive procedure should be used.

28. Ultrasound (US) guided percutaneous nodal sampling-

30. CT offers great anatomic detail, e.g. relationship of the tumour to the fissures (which may determine the type of resection), to mediastinal structures, or to the pleura and chest wall. Carefulness to exclude a patient from surgery based on CT criteria alone

31. Magnetic resonance (MRI) imaging for the assessment of superior sulcus tumours, relation to vascular structures…

33. PET-CT False-negativePET findings: little FDG avidity of the primary tumour, presence of a central tumour or of centrally located N1 nodes, both of which may obscure nearby existing mediastinal LN mts. False-positive findings - FDG uptake is not tumour specific, and can be found in all active tissues with high glucose metabolism, in particular inflammation. Clinically relevant FDG-avid mediastinal LNs should always be examined with the most appropriate tissue sampling technique.

34. Invasive diagnostic proceduresCommon sites for tissue sampling A tissue diagnosis of lung cancer is crucial to differentiate nonsmall cell lung cancer (NSCLC) from small cell lung cancer.

35. Invasive diagnostic proceduresA) Endoscopy Bronchoscopy remains a standard in patients with intra-thoracic disease, routinely performed, provides important diagnostic as well as staging information. Evaluation of the endobronchial extension of the tu, which can be decisive for the extent of resection or for RT planning. Autofluorescence bronchoscopy aids in the diagnosis of pre-invasive lesions and early lung cancers,

36. A) Endoscopy Conventional or blind transbronchial needle aspiration – TBNA - Enlarged LNs on CT Endoscopic ultrasonography: EUS–FNA and EBUS–TBNA improved accuracy of endoscopic mediastinal LN sampling techniques. Suboptimal NPV 60% to 80%, requires a confirmatory surgical staging procedure in the case of a nonmalignant NA. EUS–FNA - preferred for staging of inferior mediastinal LNs

37. Invasive diagnostic procedures Endobronchial and endoscopic ultrasound have become established for the mediastinal staging of NSCLC. Surgical biopsy and mediastinoscopy are still considered to be gold standard investigations: Cervical mediastinoscopy - for staging the upper mediastinal LNs in early stage I/II LC Anterior mediastinotomy aortopulmonary window and para-aortic LNs (5,6) Video-assisted thoracic surgery (VATS) - useful add-on to cervical mediastinoscopy - reaches inferior mediastinal nodes

38. Staging of Lung CancerTNM7 Classification (IASLC 2009.)

39. T1a – T2b new (according to IASLC) T1a T1b T2a T2b Spreading limited to the bronchial wall, may extend proximal to the main bronchus Tu ≤2cm Tu ≥3cm, ≤5cm Tu ≥2cm, ≤3cm Tu ≤5cm Invasion of the visc. pleura Tu involves main bronchus, 2cm or more distal to carina Associated atelectasis or Obstruct.pneumonitis that does not involve entire lung Tu ≥5cm, ≤7cm (with or without other descriptors Tumour ≤2cm and Tu ≥2cm, ≤3cm Any bronchoscopic invasion should not extend proximal to the lobar bronchus

40. T3 – T4 new (according to IASLC) Chest wall invasion including Pancoast tu without invasion of vertebral body or spinal canal, subclavian vessels, brachial plexus (c8 or above) T3 T4 Tu invades trachea and/or SVC or other great vessel Tu ≥7cm Tu invades aorta and/or Rec.lar.n. Phrenic n. or par.peric. invasion Tu involves carina Invasion of par.med.pleura Tu invades adj. vert.body Additional tu nodule(s) in the lobe of the primary Diaphragmatic invasion Tu invades esophagus, Mediastinum and/or heart Pancoast tu with invasion of vert. body or spinal canal, subcl. vessels, brachial plexus c8 or above) Tu accompanied by ipsilat. nod., different lobe Tu in the main bronchus Less than 2cm from the carina and/or assoc. atelectasis or Obstr.oneumonitis of the entire lung

41. N status N1 - ipsilateral hilar N2 - ipsilateral mediastinal and / or - subcarinal N3 - contralateral mediastinal / hilar - supraclavicular bilateral - Scalenus lymph node bil.

42. M status M1b M1a Distant mts Brain Contralateral pulmonary nodules Primary tu Distant nodal mts (beyond regional nodes) Bone Adrenal Liver Malignant pericardial effusion/nodules Malignant pleural effusion/nodules

43. Staging of NSCLC – tumour resectability and fitness for Surgery The aim is to determine the stage as accurately as possible: to avoid false-positive interpretations (leading to a false stage III/IV dg in early stage pts), and false-negative interpretations (leading to a false early stage dg in pts with mediastinal LN disease). Resectability needs to be estimated as precisely as possible. Fitness for Surgery: comorbidities, assessment of pulmonary reserve, age…

44. Surgery of Stage I/II Non small cell Lung Cancer (NSCLC) Cornerstone of early stage NSCLC treatment, but only in stage I 5-year survival over 50% Lobectomy including systematic lymph node dissection is standard of care for stage I and II NSCLC (resulting in a 5-year survival for IA ranging from 69% to 89%, for IB from 52% to 75%, for IIA from 45% to 52% and 33% for IIB). Pneumonectomy rarely indicated in these stages

45. Lung Cancer – NSCLC-Stage IA,B – T1N0, T2N0 -

47. Patients unfit for lobectomy should undergo a segmentectomyVATS lobectomy more and more applied in many centres for tumours generally <5 cm; similar locoregional recurrences and better survival

48. Surgery of Lung Cancer – NSCLC- stage IIB – T3N0 Tumors proximally of carina Pneumonectomy, sleevelobectomy, sleevePneumonectomy 5-year survival rate 30% to 40% (Martini et al, Lung Tumors, Springer-Verlag,1988). (Pitz et al,Ann Thorac Surg 62:1016, 1996).

49. Locally advanced NSCLC (stage III) Locally advanced or stage III disease accounts for 30% of patients with NSCLC. Treatment of stage III NSCLC very difficult and controversial mainly because of the large heterogeneity in this group.

50. Locally advanced NSCLC (stage III) Stage IIIA: 5-year survival - 24% Stage IIIB: 5-year survival rate - 9% Stage IIIA NSCLC (10%–15% ) - heterogeneous group from apparently resectabletumours with occult nodal microscopic metastasis to unresectable, bulky multistation nodal disease. stageIIIA– centrally located RESECTABLE stage IIIB T4 N3 NOT RESECTABLE

51. Subclassification of stage III NSCLC

53. Surgery of Non small cell Lung Cancer- superior sulcus tumor - IIIA T3-4 N0

54. Stage IIIA – Downstaging:Tumour becomes Resectable Staging PET-CTPET-CTafter induction th

55. Surgery of NSCLC with solitary metastasis Solitary metastasis: Brain Lung Adrenal gland

56. SCLC – Diagnosis and Staging medical history and physical examination, chest X-ray, complete blood count including differential count, liver, lung and renal function tests, lactate dehydrogenase (LDH) and sodium levels CT scan of the chest and abdomen including the liver and adrenal glands Symptoms or abnormal physical examination suggesting metastasis - additional tests may include: bone scintigraphy, CT scan or MRI of brain, bone marrow aspiration and biopsy

57. Small Cell Lung Cancer - SCLC Classification: - IASLC proposed to apply TNM 7 revised VALSG staging system Limited Disease vs Extensive Disease (tumour confined to one hemithorax with mts in regional LNs) (distant mts)

58. Surgery of SCLC Very Limited Disease (T1–2, N0) as primary treatment Limited Disease if Lobectomy possible? Residual tumour after ChemoRadiotherapy completed if excision, sublobar resection or Lobectomy possible