Lung Cancer

Introduction

• Leading cause of cancer deaths in men and women
• Incidence peaks at 55 to 65yo
• Adenocarcinoma has become the most common and incidence of small cell lung cancer is on the decline

Frequency and survival

Small cell vs. NSLCL

• Small cell shows neuroendocrine properties absent in NSCLC
  • Production of ACTH, vasopressin, atrial natriuretic factor, gastrin-releasing peptide
• Small cell have RB mutations in >90% and never KRAS or EGFR mutations
• Both have high rates of p53 mutations
• SCLC’s are initially very responsive to chemotherapy and radiotherapy but ultimately relapse
• NSCLC have objective tumor shrinkage from radiotherapy 30-50% of the time and response to chemo in 20-35% of cases
• SCLC usually spread before diagnosis and not amenable to surgery
• NSCLC are usually localised at diagnosis and may be cured with surgery and/or radiotherapy

Smoking and anatomical site

• 85% of lung cancers occur in people who have smoked
• The most common lung cancer in non-smokers, in women and in young patients is adenocarcinoma
• Squamous and small cell lung cancers usually present as central masses with endobronchial growth
• Adenocarcinomas and large cell cancers tend to be peripheral with pleural involvement
• Squamous and large cell cancers cavitate in 10-20%
• Bronchioloalveolar carcinoma is a subtype of adenocarcinoma that spreads along alveoli without invasion and may appear as a distinct mass, diffuse multinodular lesion, a fluffy infiltrate or as ground glass opacification on CT

Smoking

• Relative risk is 13 fold by active smoking and 1.5 x for passive exposure
• COPD further increases the risk of lung cancer
• Women have a higher risk per given exposure than men (1.5x)
• Risk directly related to pack years

Clinical manifestations

• 5-15% identified while asymptomatic
• Central or endobronchial tumor growth
  • Cough, haemoptysis, wheeze, stridor, dyspnoea and post-obstructive pneumonitis
• Peripheral growth
  • Pleurisy, dyspnoea on a restrictive basis and lung abscess symptoms with cavitation
• Regional spread of tumor in the thorax
  • Tracheal obstruction, oesophageal compression with dysphagia, recurrent laryngeal nerve palsy, phrenic nerve paralysis, Horner’s syndrome
• Malignant pleural effusion may present with dyspnoea
• Pancoast’s syndrome
  • Results from local extension into lung apex with involvement of the 8^th cervical and 1^st/2^nd thoracic nerves, with shoulder pain radiating down ulnar distribution often with radiological destruction of 1^st and 2^nd ribs
• Often Horner’s and Pancoast’s co-exist
• SVC syndrome from vascular obstruction

Clinical manifestations

• Extrathoracic metastasis
  • Found in >50% of patients at autopsy with squamous cell carcinoma, 80% of patients with adenocarcinoma and >95% of patients with small cell carcinoma
  • Common clinical presentations are:
    • Brain mets – Headache, nausea, focal neurology
    • Bony mets – Pain, pathological fractures
    • Bone marrow – Pancytopaenia, leukoerythroblastosis
    • Liver mets – Liver dysfunction, biliary obstruction, anorexia and pain
    • Lymph node mets – Supraclavicular, axilla and groin
    • Spinal cord compression from epidural or bone metastases
    • Adrenal metastases are common but rarely present clinically

Clinical manifestations

• Paraneoplastic syndromes
  • Anorexia, cachexia, weight loss, fever and immunosupression occur with unknown cause
  • Endocrine syndromes (12% of patients)
    • PTH or PTHrP from squamous cell carcinomas leading to hypercalcaemia, hypophosphataemia
    • SIADH from small cell lung cancer with hyponatraemia
    • ACTH from small cell cancer with resultant hypokalaemia (rather than Cushing’s)
  • Skeletal-connective tissue syndromes
    • Clubbing in 30% of cases (usually NSCLC)
    • Hypertrophic pulmonary osteoarthropathy in 1-10% of cases (usually adenocarcinoma)
      • Periostitis and clubbing causing pain, tenderness and swelling
  • Neurologic-myopathic syndromes (1%)
    • Eaton-Lambert syndrome
    • Retinal blindness in small cell cancer
    • Peripheral neuropathy, subacute cerebellar degeneration, cortical degeneration and polymyositis in all cancer subtypes
  • Haematological manifestations in 1-8%
    • Migratory venous thrombophlebitis (Trousseau’s syndrome)
    • Non-bacterial thrombotic (marantic) endocarditis with arterial emboli
    • DIC

Screening

• National Lung Cancer Screening Trial (NLST)
  • Annual CXR shows no benefit
  • 20% reduction in mortality with annual non-contrast helical CT in high-risk patients (current or previous heavy smokers 55 to 74yo) vs. annual CXR
  • 6.7% reduction in all-cause mortality in CT screened group
  • Recommendation is patients 55-80yo with at least 30 pack year smoking history and have smoked in the past 15 years
  • High false-positive rate (96.4%) leading to high rates of follow-up Ix and potentially harmful invasive tests

Establishing diagnosis

• Tissue diagnosis essential either via bronchial or transbronchial biopsy, node biopsy by mediastinoscopy, operative specimen during surgical resection, percutaneous biopsy, FNA of masses using CT guidance or from pleural effusion cel block

Staging patients

• Anatomic + Physiologic staging (ability to withstand therapy)
• NSCLC
  • TNM anatomical staging with measure of resectability
  • Physiological staging determines operability
• Small cell 
  • Limited-stage (30% of patients) = confined to one hemithorax and regional lymph nodes (mediastinal, contralateral hilar and ipsilateral supraclavicular)
  • Extensive-stage (70% of patients) = disease exceeding this
  • Limited staging partly based on single curative radiotherapy port and thus contralateral supraclavicular/recurrent laryngeal/SVC obstruction may all form part of limited stage disease while cardiac tamponade, pleural effusion and bilateral pulmonary parenchymal involvement are classed as extensive as the organs in question would not safely tolerate curative radiotherapy doses

Management of occult carcinomas

• In the uncommon situation of malignant cells on sputum or bronchial washing cytology
• Lesion must be localised
  • 90% can be localised by bronchoscopy and collection of brushings

Management of solitary pulmonary nodule

• X-ray density surrounded by normal aerated lung, with circumscribed margins, of any shape, 1-6cm in size
• 35% of these are malignant, most being primary lung cancer
• <1% are malignant in non-smoker under 35
• Need full history, smoking history and comparison with old CXR/CT
  • If benign appearance or no change in >2 years – Monitor (see below)
  • If growing or change in shape – resect
  • If malignancy cannot be ruled out – CT
    • If CT appears benign (see below) – Monitor
    • If CT appears suggestive of malignancy – Resect
    • If inconclusive – Consider biopsy or PET scan
      • If benign – Monitor
      • If suggestive of malignancy – Resect
      • If inconclusive – Resect

Management of SPN

• If no clear diagnosis, the following factors would favor resection:
  • Age >= 35
  • Relatively large lesion
  • Lack of calcification
  • Chest symptoms
  • Associated atelectasis, pneumonitis or adenopathy
  • Growth of lesion compared to old scans
  • Positive PET scan

Fleishner guidelines

Low risk = <5% risk of cancer. Younger, less smoking, smaller nodule size, regular margins
and non-upper lobe location

High risk = >5% risk of cancer. Older, heavy smoker, larger nodule size, irregular or spiculated
margins, upper lobe location

Management of SPN

• Only 2 factors are reliable predictors of benign nature
  • Lack of growth over >2 years
  • Calcification patterns
    • Dense central nidus, multiple punctate foci and bull’s eye (granuloma) and popcorn ball (hamartoma) calcifications
• If decision to monitor
  • Non-smoker patients under 35 can be followed with serial CT every 3 months for 1 year and then yearly – if any growth seen need biopsy.
  • If >35 or any smoking history histological diagnosis is required as slow-growing bronchioloalveolar carcinoma can be PET negative
    • Sample may be taken at resection, or if poor operative candidate, via VATS or transthoracic fine needle biopsy

Management of incidental ’ground glass’

• Many are in fact bronchioloalveolar carcinoma
• Require transbronchial biopsy for histological diagnosis

Last Updated on October 28, 2020 by Andrew Crofton