Early Detection of Lung Cancer Dr. Shanthi Paramothayan Consultant Respiratory Physician St. Helier University Hospital 14 th June 2011

Aim and Objectives of this session Aims and Objectives: Aims and Objectives:  Risk Factors: identify high risk patients  Clinical Presentation of lung cancer  Classification of lung cancers  Diagnosis including investigations  Staging of lung cancers  Management

Benign Lung Tumours Hamartoma Hamartoma Arterio-venous malformations (AVMs) Arterio-venous malformations (AVMs) Carcinoid tumour Carcinoid tumour Granuloma Granuloma Patients often asymptomatic. Incidental finding on CXR (solitary pulmonary nodule) Patients often asymptomatic. Incidental finding on CXR (solitary pulmonary nodule) Malignancy needs to be excluded Malignancy needs to be excluded

Importance of Lung Cancer Incidence: 40,000 new cases of lung cancer /year Incidence: 40,000 new cases of lung cancer /year Leading cause of cancer death world wide Leading cause of cancer death world wide Third commonest cause of death in UK Third commonest cause of death in UK 32,000 deaths/year 32,000 deaths/year North South divide: higher prevalence in North North South divide: higher prevalence in North Higher in lower socio economic groups Higher in lower socio economic groups  with age  with age Commoner in men but  in women Commoner in men but  in women

Risk Factors for Lung Cancer Smoking (pack yrs), early onset worse Smoking (pack yrs), early onset worse  latent period of 30 years Passive smoking (early exposure) Passive smoking (early exposure) Asbestos Asbestos  latent period of years Radiation Radiation ArsenicCoal tar Petroleum products ArsenicCoal tar Petroleum products Family History (genetic factors) Family History (genetic factors) Scar tissue Scar tissue

Poor Prognosis in Lung Cancer WHY? No significant improvement in mortality for many years

Poor Prognosis in Lung Cancer Why? Why?  No screening for lung cancer  Late presentation  Insufficient resources/emphasis towards Smoking Cessation  Poor surgical rates (10-15% v 20% in USA)  Co-morbidity: limits treatment options How can we improve mortality in lung cancer in the 21 st Century?

What do you think…….?  Should cigarettes be banned?  What else can we do to stop smoking?  Should we screen for lung cancer?  How can we improve early referral for suspected lung cancer?  How can we improve referral for surgery – hence improve curative rates?

Smoking Cessation Stop children/teenagers from starting to smoke: how? Stop children/teenagers from starting to smoke: how? Stop current smokers Stop current smokers Education Education Political willingness: smoking ban Political willingness: smoking ban Resources: smoking cessation clinics Resources: smoking cessation clinics Doctors: Advise strongly, refer to smoking cessation clinic, prescribe NRT Doctors: Advise strongly, refer to smoking cessation clinic, prescribe NRT

Screening For Lung Cancer How? CXR, CT thorax ? Mobile units How? CXR, CT thorax ? Mobile units How Often? yearly? How Often? yearly? In what population? Smokers? Family history? In what population? Smokers? Family history? False positives and false negatives False positives and false negatives Cost effective? Cost effective?

Case 1 50 year old Asian man 50 year old Asian man 30 pack year history of smoking 30 pack year history of smoking Strong family history of malignancy Strong family history of malignancy Persistent cough for > 6 months Persistent cough for > 6 months Frequent visits to GP: several course of antibiotics Frequent visits to GP: several course of antibiotics Admitted to St. Helier Hospital with haemoptysis and weight loss Admitted to St. Helier Hospital with haemoptysis and weight loss Cervical lymphadenopathy, clubbed Cervical lymphadenopathy, clubbed

Case 1 Tumour seen right upper lobe and right intermediate bronchus as Bronchoscopy Tumour seen right upper lobe and right intermediate bronchus as Bronchoscopy Poorly differentiated adenocarcinoma Poorly differentiated adenocarcinoma Referred to RMH: Stage 4 disease, so palliative chemotherapy only Referred to RMH: Stage 4 disease, so palliative chemotherapy only Early chest X-ray and referral after onset of symptoms may have made a difference ! Early chest X-ray and referral after onset of symptoms may have made a difference !

Case 2 40 year old woman, non smoker 40 year old woman, non smoker Persistent productive cough despite several courses of antibiotics Persistent productive cough despite several courses of antibiotics CXR abnormality: not resolving after several weeks CXR abnormality: not resolving after several weeks Admitted to hospital with severe SOB and chest pain Admitted to hospital with severe SOB and chest pain Found to have extensive CXR changes and pericardial effusion Found to have extensive CXR changes and pericardial effusion

Case 2 Pericardial effusion drained (pericardial window) Pericardial effusion drained (pericardial window) Bronchoscopy and BAL: bronchoalveolar cell carcinoma Bronchoscopy and BAL: bronchoalveolar cell carcinoma Stage 4 disease Stage 4 disease Referred for palliative chemotherapy Referred for palliative chemotherapy

Case 3 56 year old woman, ex smoker, large goitre 56 year old woman, ex smoker, large goitre Found to have a Nodule (Solitary pulmonary nodule) on CT scan = incidental Found to have a Nodule (Solitary pulmonary nodule) on CT scan = incidental Interval scan if nodule < 1 cm or looks benign for up to 2 years Interval scan if nodule < 1 cm or looks benign for up to 2 years PET scan +/ CT guided biopsy if > 1 cm PET scan +/ CT guided biopsy if > 1 cm If suspicious, then can consider wedge resection or lobectomy If suspicious, then can consider wedge resection or lobectomy

Reasons for Late Presentation Patient unaware of importance of symptoms: presents late to GP Patient unaware of importance of symptoms: presents late to GP Doctors unaware of early symptoms and signs of lung cancer: delayed referral to specialist Doctors unaware of early symptoms and signs of lung cancer: delayed referral to specialist Many symptoms non-specific and common in smokers Many symptoms non-specific and common in smokers Delayed investigations: lack of resources Delayed investigations: lack of resources Two week Rule referral New Initiative: Fast Track of Two Week Rule

Who needs CXR and referral? Smoking history Smoking history Strong family history Strong family history Symptoms not resolving (eg persistent cough) Symptoms not resolving (eg persistent cough) Haemoptysis Haemoptysis Systemic symptoms Systemic symptoms

The Patient Pathway for suspected lung cancer Patient referred as 2 week rule Patient referred as 2 week rule Seen by specialist within 14 days of receiving referral Seen by specialist within 14 days of receiving referral Investigations within 28 days of referral Investigations within 28 days of referral Treatment within 62 days of referral Treatment within 62 days of referral All patients discussed at weekly lung cancer MDT All patients discussed at weekly lung cancer MDT Breaches counted Breaches counted Tumour working group meet 3 monthly Tumour working group meet 3 monthly

Reasons for poor surgical rates in UK Late presentation Late presentation Co-morbidity: IHD, COPD Co-morbidity: IHD, COPD

Clinical Presentation of Lung Cancer What is the commonest symptom? What is the commonest symptom? What sort of patients should you be worried about? What sort of patients should you be worried about? Is there a problem with you getting CXR? Is there a problem with you getting CXR? Do you have a problem referring patients to a respiratory consultant? Do you have a problem referring patients to a respiratory consultant?

Clinical Presentation of Lung Cancer Lung symptoms: Lung symptoms:  Persistent cough (80%)  Dyspnoea (60%)  Haemoptysis  Chest pain  Wheeze (monophonic wheeze)  Stridor (large airway obstruction)  Non-resolving pneumonia

Clinical Presentation of Lung Cancer Other Symptoms of concern: Other Symptoms of concern:  Hoarse voice  Lymphadenopathy  Hyponatraemia: inappropriate ADH  Hypercalcaemia Systemic Symptoms Systemic Symptoms  weight loss  fever  lethargy

Clinical Examination Weight and height (BMI): weight loss Weight and height (BMI): weight loss Hoarse voice Hoarse voice Clubbing and HPOA Clubbing and HPOA Horner’s syndrome Horner’s syndrome Lymphadenopathy Lymphadenopathy Tracheal deviation Tracheal deviation SVC obstruction SVC obstruction Pleural effusion Pleural effusion Lungs: monophonic wheeze Lungs: monophonic wheeze Liver: hepatomegaly, jaundice Liver: hepatomegaly, jaundice Neurological examination Neurological examination

Performance Status WHO (Zubrod) scale 0Asymptomatic 1 Symptomatic but ambulatory (able to carry out light work) 2 In bed< 50% of day (unable to work but able to live at home with some assistance) 3 In bed > 50% of day (unable to care for self) 4 Bedridden

Referring patients according to 2 week rule pathway MORE LIKELY LESS LIKELY Significant smoking history Non smoker Older patient Younger patient Prolonged history of symptoms Short history of symptoms Non-infective symptoms Infective symptoms Radiology: tumour Radiology: infection

Malignant Lung Cancers Primary: Primary:  Bronchogenic: from epithelium of bronchial mucosa (95%)  Bronchoalveolar: from alveolar cells  Mesothelioma: from pleura Secondary (Metastases): Secondary (Metastases):  PulmonaryColon  BreastKidney  ThyroidProstate

Pathophysiology of lung cancer Progressive changes in bronchial mucosa Progressive changes in bronchial mucosa Squamous metaplasia of bronchial epithelium Squamous metaplasia of bronchial epithelium Dysplasia Dysplasia Malignant cells Malignant cells Local invasion: Local invasion:  adjacent lungpericardium  pleuraribs and muscle Distant metastases (lymphatics and blood) Distant metastases (lymphatics and blood)  lymph node adrenals  liverbone brain

Effects of Local Spread Pleural involvement: chest pain, pleural effusion Pleural involvement: chest pain, pleural effusion Rib erosion: bony pain Rib erosion: bony pain Lymphadenopathy: intrathoracic, supraclavicular Lymphadenopathy: intrathoracic, supraclavicular Pancoast’s tumour: apical, involves brachial plexus Pancoast’s tumour: apical, involves brachial plexus Horner’s syndrome: involvement of lower cervical sympathetic ganglion (ptosis, miosis, enopthalmos, anhidrosis) Horner’s syndrome: involvement of lower cervical sympathetic ganglion (ptosis, miosis, enopthalmos, anhidrosis)

Effects of Local Spread Recurrent Laryngeal nerve palsy: hoarse voice, bovine cough Recurrent Laryngeal nerve palsy: hoarse voice, bovine cough Phrenic nerve palsy: raised hemi-diaphragm Phrenic nerve palsy: raised hemi-diaphragm SVC obstruction: invasion of superior mediastinum (headache, pain, facial congestion, distended neck veins, upper limb oedema) SVC obstruction: invasion of superior mediastinum (headache, pain, facial congestion, distended neck veins, upper limb oedema) Oesophageal compression: dysphagia Oesophageal compression: dysphagia Pericardial involvement: cardiac arrhythmias Pericardial involvement: cardiac arrhythmias

Distant Metastases Bone: pathological fractures, severe pain, hypercalcaemia, spinal cord compression Bone: pathological fractures, severe pain, hypercalcaemia, spinal cord compression Liver: jaundice, abnormal LFTs Liver: jaundice, abnormal LFTs Brain: convulsions, headaches, confusion, hemiparesis, personality change Brain: convulsions, headaches, confusion, hemiparesis, personality change Lung: Ipsilateral or contralateral lung Lung: Ipsilateral or contralateral lung Adrenal: rarely adrenal insufficiency Adrenal: rarely adrenal insufficiency Skin: nodules Skin: nodules

Bronchogenic Lung Cancer Non small cell lung cancer (NSCLC): Non small cell lung cancer (NSCLC):  Squamous cell carcinoma  Adenocarcinoma  Large cell (undifferentiated) Small cell lung cancer (SCLC) Small cell lung cancer (SCLC)

NSCLC Squamous Cell Carcinoma (30%) Squamous Cell Carcinoma (30%)  develops in large central airways  Cavitating with necrosis and haemorrhage  PTH secreting: hypercalcaemia Adenocarcinoma (30%) Adenocarcinoma (30%)  arise from mucous cells of the epithelium  Less associated with smoking  More peripheral, grow slowly, metastasize late  Bronchoalveolar cell carcinoma Large Cell (15%) Large Cell (15%)  poorly differentiated  highly aggressive, metastasize early

SCLC Also known as “oat cell carcinoma” Also known as “oat cell carcinoma” 25% of all lung cancers 25% of all lung cancers Arise from the Kulchitsky cells (endocrine cells): part of APUD Arise from the Kulchitsky cells (endocrine cells): part of APUD Secrete polypeptide hormones Secrete polypeptide hormones Highly aggressive, grows rapidly and metastasizes early Highly aggressive, grows rapidly and metastasizes early Very poor prognosis Very poor prognosis

Non-metastatic Manifestations SIADH: hyponatraemia (SCLC) SIADH: hyponatraemia (SCLC) ACTH: Cushing’s syndrome (SCLC) ACTH: Cushing’s syndrome (SCLC) PTH: hypercalcaemia (SCC) PTH: hypercalcaemia (SCC) Clubbing Clubbing Hypertrophic pulmonary osteoarthropy (HPOA) Hypertrophic pulmonary osteoarthropy (HPOA) Neurological manifestations: Neurological manifestations:  Cerebellar degeneration  Myopathies  Neuropathies  Myasthenic syndrome (Eaton-Lambert syndrome)  DIC and other haematological abnormalities

Investigations Radiology: Radiology:  CXR  Staging CT scan (thorax and abdomen)  Brain CT scan (neurological symptoms or signs)  MRI scan (nerve/rib involvement, sc compression)  Bone scan (bone pain, hypercalcaemia)  PET scan (staging)

PET scan Essential prior to radical treatment (surgery or radiotherapy) Essential prior to radical treatment (surgery or radiotherapy) May upstage or downstage a tumour May upstage or downstage a tumour Uptake of 2-deoxyglucose labelled with fluorine- 18 by metabolically active tissue Uptake of 2-deoxyglucose labelled with fluorine- 18 by metabolically active tissue Sensitivity for metastases: 95% Sensitivity for metastases: 95% Specificity for metastases: 83% Specificity for metastases: 83% Not good at detecting brain metastases Not good at detecting brain metastases Not good for slowly growing tumours Not good for slowly growing tumours

Investigations Histology / cytology: Histology / cytology:  bronchoscopy: biopsy, brushings, washings  CT / US guided biopsy (lung mass)  pleural fluid  bone biopsy  lymph node biopsy / FNA  mediastinoscopy  liver biopsy

Investigations Lung function tests (to assess severity of COPD) Lung function tests (to assess severity of COPD) ECG ECG ECHO (LV function) ECHO (LV function) BLOODS: BLOODS:  FBC U+Es LFTs  clotting bone profile Ca 2+

Summary Lung cancer is an important cause of morbidity and mortality worldwide Lung cancer is an important cause of morbidity and mortality worldwide Presentation is late, prognosis is poor Presentation is late, prognosis is poor Surgery offers best chance of survival Surgery offers best chance of survival Radical Radiotherapy is an alternative Radical Radiotherapy is an alternative Screening not currently done: ? Should we screen for lung cancer? Screening not currently done: ? Should we screen for lung cancer? How can we improve early referral from primary care? How can we improve early referral from primary care?

Any Questions?

Staging of NSCLC

New Classification T1 a and b (at 2 cm cut point) T1 a and b (at 2 cm cut point) T2a and T2b (at 5 cm cut point) T2a and T2b (at 5 cm cut point) T3 > 7 cm, additional tumour nodules in same lobe as primary lung. T3 > 7 cm, additional tumour nodules in same lobe as primary lung. T4: additional tumour nodules in ipsilateral lobes T4: additional tumour nodules in ipsilateral lobes M1a: tumour nodules in opposite lung and pleural or pericardial involvement M1a: tumour nodules in opposite lung and pleural or pericardial involvement M1b: distant metastases M1b: distant metastases

Staging of SCLC Limited: Limited:  Confined to the thorax Extensive: Extensive:  Distant metastases

Management of lung cancers All patients discussed at lung cancer MDT All patients discussed at lung cancer MDT  respiratory physicianmedical oncologist  radiologistclinical oncologist  histopathologistLung cancer nurse  Thoracic surgeonPalliative physician  MDT Co-ordinator Management depends on: Management depends on:  histologyradiological staging  performance statuslung function

Management of NSCLC Depends on: Depends on:  Radiological Staging  Histology  Performance status  Lung function

Management of NSCLC Curative intent: Curative intent:  Surgery  Radiotherapy  Chemotherapy Palliative: Palliative:  Radiotherapy  Chemotherapy  Other: endobronchial stents, laser, pleurodesis

Management of SCLC Limited: Limited:  Chemotherapy  Occasionally radiotherapy  Palliation Extensive: Extensive:  Chemotherapy  Palliation

Surgery for Lung Cancer Surgical resection best chance of cure: <15% rate Surgical resection best chance of cure: <15% rate Aim: complete resection of all cancer tissue Aim: complete resection of all cancer tissue 5 year survival < 25% 5 year survival < 25% Surgical procedures: Surgical procedures:  Wedge resection: part of lobe removed  Lobectomy: one lobe removed  Pneumonectomy: one lung removed  Morbidity and mortality considerable  Adjuvant chemotherapy + radiotherapy

Chemotherapy for lung cancer Treatment of NSCLC / SCLC: prolongs life, rarely curative Treatment of NSCLC / SCLC: prolongs life, rarely curative Palliative for NSCLC / SCLC: symptom relief Palliative for NSCLC / SCLC: symptom relief Often used together with radiotherapy Often used together with radiotherapy Neo-adjuvant : given prior to surgery to downstage tumour (inoperable to operable) Neo-adjuvant : given prior to surgery to downstage tumour (inoperable to operable) Adjuvant: post surgery to reduce risk of recurrence Adjuvant: post surgery to reduce risk of recurrence

Side Effects of Chemotherapy Bone marrow : Bone marrow :  Neutropeniathrombocytopeniaanaemia Immunosupression: Immunosupression:  Infectionsepsis Other: Other:  Nauseavomitinganorexia  Hair lossskin changes  Other symptoms related to specific agents

Radiotherapy for lung cancer Radical: high dose, curative intent (CHART) Radical: high dose, curative intent (CHART) Palliative: low dose, symptom control Palliative: low dose, symptom control  Pain at tumour siteBony metastases  Spinal cord compression Prior to surgery: de-bulking, down-staging tumour Prior to surgery: de-bulking, down-staging tumour Combined modality: with chemotherapy Combined modality: with chemotherapy Post surgery: improve long term survival (27% 5 year survival) Post surgery: improve long term survival (27% 5 year survival)

Side effects of Radiotherapy Lung: severe SOB Lung: severe SOB  Pneumonitis  fibrosis Heart Heart Oesophagus: Oesophagus:  Dysphagia

Palliative Care Palliative Care Team: Palliative Care Team:  ConsultantNurses  Community nurses Social worker  Occupational therapistPhysiotherapist  Inpatient care Outpatient care  Hospice Home visits

Palliative Care Symptom Control: Symptom Control:  Pain: pain ladder, opiates, syringe driver  Cough: opiates  SOB: O 2, morphine, diazepam  Secretions: hyoscine (pump  Constipation: laxatives  Decreased appetite: steroids  Depression: antidepressants

Palliative Procedures For relief of breathlessness: For relief of breathlessness:  Endobronchial stents  Laser phototherapy  Drainage of pleural fluid  Medical or VATS pleurodesis

Management of SVC Obstruction Severe / urgent: Severe / urgent:  Radiologist to insert SVC stent  Radiotherapy  Dexamethasone  Anticoagulate Non-severe: Non-severe:  Dexamethasone  Anticoagulate  Radiotherapy  SVC stent

Bronchoalveolar cell carcinoma Presents with increasing breathlessness, productive cough Presents with increasing breathlessness, productive cough CXR: pneumonic process (alveolar shadowing) CXR: pneumonic process (alveolar shadowing) Usually peripheral Usually peripheral Chemotherapy Chemotherapy Poor prognosis Poor prognosis

Mesothelioma Malignant tumour of pleura Malignant tumour of pleura Risk factor: asbestos exposure Risk factor: asbestos exposure Lag of 30 – 40 years Lag of 30 – 40 years Incidence rising until 2015 Incidence rising until 2015 Very poor prognosis Very poor prognosis

Clinical presentation and Diagnosis of Mesothelioma Severe chest pain (chest wall) Severe chest pain (chest wall) Anorexia and weight loss Anorexia and weight loss Increasing breathlessness Increasing breathlessness CXR and CT: thickened pleura, contraction of hemithorax CXR and CT: thickened pleura, contraction of hemithorax Pleural Biopsy: Pleural Biopsy:  Abram’s needle  VATS  CT -guided

Histopathology of mesothelioma Epithelioid: better prognosis (18 months) Epithelioid: better prognosis (18 months) Sarcomatous: poor prognosis (6 months) Sarcomatous: poor prognosis (6 months) Mixed: intermediate prognosis (12 months) Mixed: intermediate prognosis (12 months)

Management of mesothelioma Surgery Surgery Radiotherapy Radiotherapy Chemotherapy Chemotherapy Palliation Palliation

Summary Lung cancer is an important cause of morbidity and mortality worldwide Lung cancer is an important cause of morbidity and mortality worldwide Presentation is late, prognosis is poor Presentation is late, prognosis is poor Surgery offers best chance of survival Surgery offers best chance of survival Screening not currently done: ? Should we screen for lung cancer? Screening not currently done: ? Should we screen for lung cancer? How can we improve early referral from primary care? How can we improve early referral from primary care? Multidisciplinary approach essential Multidisciplinary approach essential Palliative care important Palliative care important