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Lung Cancer: Update on Diagnosis and Treatment

John Thomas Phelan II, MD

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Epidemiology 1.5 – 2 million new cases / yr

worldwide In US, 164,100 new cases / yr;

156,900 deaths per year

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Epidemiology In US, rising incidence in women In US, lung cancer mortality in

women > breast ca mortality In US, lung cancer = 15% of cancer

in men and women

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Epidemiology

In US, only 1/3 of pts are eligible for surgery w/ curative intent

10% - 20% occur in nonsmokers 25% - 35% of these can be

attributable to secondhand smoke inhalation

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Etiology Tobacco smoke !!!! Increased risk for GU, upper respiratory

tract and upper GI ca Stopping smoking reduces risk, but only

after > 6 yrs Inc’d death rate w/ increased exposure

(ie, more smoked = greater risk of death from lung cancer)

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Classification: Non small cell lung ca vs small cell lung ca

NSCLC = 80% of cases, small cell lung ca = 20% of cases

NSCLC: 4 histologic subtypes: squamous cell, adenocarcinoma, large cell, bronchioloalveolar

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Classification: Non small cell lung ca vs small cell lung ca

Squamous cell: 50% - 60% = proximal / hilar in location. Produce obstruction / pneumonitis / hemoptysis

Adenocarcinoma: More likely peripheral

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Classification: Non small cell lung ca vs small cell lung ca

Bronchioloalveolar: Originates in alveolar cells. Most common lung ca in nonsmokers.

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Classification: Non small cell lung ca vs small cell lung ca

Small cell: Usually proximal / central. Rapidly growing / disseminating. Limited to thorax in only 25% of cases

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Diagnostic / Presenting Features Change in pulmonary habits,

especially in established smoker (ie cough, shortness of breath, shoulder pain, hoarseness)

Extrapulmonary: paraneoplastic syndromes (2% of lung cancer pts), bone pain, CNS sxs, unexplained wt loss

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Diagnosis / Staging

Chest X-ray: Ease. Assess atelectasis, peripheral nodules, rib erosion

Chest CT: Assess mediastinum, vertebral bodies, chest wall.

PET scan: Cases by case basis

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Staging

Stage = anatomic extent of disease (ie, thoracic cavity vs extrathoracic)

AJCC, UICC employ TNM (T (primary tumor), N (nodes), M (mets)) nomenclature

Staging guides treatment, establishes prognostic / outcome groups

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Staging studies Tissue confirmation: sputum

cytology, CT guided needle biopsy, bronchoscopy w / brushing / lavage and biopsy, VATS, open thoracotomy

Abd CT: Eval for liver / adrenal mets Bone scan: Eval for occult bone mets Head MRI: Eval for occult brain mets

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Staging mediastinoscopy

Right sided mediastinal lymph node sampling to carina. Aortic arch limits left sided sampling

Mediastinal LN involvement contraindication for surgical resection

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TNM categories in lung cancer T1-T4: T1: < 3cm, surr by lung T2: > 3cm / main bronchus / visceral pleura T3: any size / invades chest wall / diaph mediast pleura / parietal pericard T4: any size / invades mediastinum /malignant effusion

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TNM categories in lung cancer N1-N3: N1: intrapulm / peribronch / hilar N2: ipsilateral mediastinal / subcarinal N3: ipsilateral or contralateral scalene / supraclavic / contralateral mediastinal / contralateral hilar

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TNM categories in lung cancer

M0 –M1: M0: No distant mets

M1: Distant mets

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Staging in small cell lung cancer

Limited stage: Disease limited to single hemithorax / encompassable by single radiation port

Extensive stage: Extrathoracic disease

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Treatment Principles (NSCLC)

Stage 1 (T1-2N0M0), stage 2 (T1-2N1M0; T3N0M0): Lobectomy, pneumonectomy, segmentectomy

Principle goal: Resect all disease, preserve maximum normal lung function

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Treatment Principles (NSCLC) Stage 3 (T3N0-2M0): Not absolute

contraindication to surgery. Successful outcome dependent on careful pt selection

Stage IIIB/IV (N3 or metastatic disease): usually not surgical candidate

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Treatment Principles (NSCLC) Unresectable stage III disease: radiation therapy

alone or concurrent chemoradiation therapy Stage IV disease: palliative chemotherapy

alone +/- radiation to palliate select sites (ie bone, brain)

Treatment goals in unresectable disease = palliation/symptom control

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Treatment Principles (SCLC)

Considered unresectable, even in seemingly early stage

Limited stage (confined to single hemithorax / radiation port): concurrent chemoradiation therapy with cisplatin /VP-16 / XRT

Prophylactic cranial radiation: Controversial, but more widely accepted

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Treatment Principles (SCLC)

Extensive stage (extrathoracic / not encompassable by single radiation port): palliative chemotherapy alone with palliative radiation to selected sites

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Treatment Facts

1) Stage 1 I NSCLC 5yr survival = 47%; stage III/IV = 2%. 2) Stage 1 SCLC 5 yr survival = 20%; stage III/IV

= 1%3) Take home message: In NSCLC, > 50% of

early stage pts die of lung ca after 5 yrs; even worse for SCLC

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Promising developments

1) Adjuvant chemotherapy improves survival in resected stage I / II pts

2) Small molecules / antibodies targeting EGFR (Epidermal Growth Factor Receptor) effects NSCLC clinical course