Danielle Press,MD

Epidemiology

• Decreasing incidence in men, stable incidence in women

• Men – 83.5 in 100,000• Women – 49.2 in 100,000• Decline likely due to public health

initiatives to stop smoking • Death rates decrease to that of

nonsmokers 10yrs after cessation

Tumor Biology

• Many mechanisms • Chromosomal loss of heterzygosity or

allelic gain • K-ras, myc, p53 mutations• Inactivation of tumor suppressor

p16INK4a (p16)• EGF receptor mutations possibly

important to response to chemotherapy

Non-Small Cell Lung Cancer (NSCLC)

• Evaluate for distant mets• Brain, contralateral lung, supraclavicular

nodes, bone, liver, adrenals • Labs: CBC, BMP, Ca, alk phos, LDH• CT or PET

• CT chest/upper abd to evaluate tumor & lymph node status

• Mediastinoscopy – gold standard fro tissue diagnosis of mediastinal lymphadenopathy

TNM Staging Non & Small Cell Lung Cancer

T1 <3cm, surround by lung or visceral pleura, no invasion of main bronchus

T2 >3cm, involves main bronchus but >2cm distal to carina; invades visercal pleura; atelectasis or obstructive pneumonitis that extends to hilar region but does not involve entire lung

T3 Any size that directly invades any of these: chest wall, diaphragm, mediastinal pleura, parietal pericardium; tumor in main bronchus <2cm from carina but no involvement of carina; atelectasis or obstructive pneumonitis of entire lung

T4 Any size that involves any of these: mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina; malignant pleural or pericardial effusion; satellite tumor nodule with ipsilateral primary tumor lobe

TNM Staging

N0 No regional lymph node mets

N1 Mets to ipsilateral peribronchial and/or ipsilateral hilar lyph nodes and involvement in intrapulmonary nodes by direct extension of primary tumor

N2 Mets to ipsilateral mediastinal and/or subcarinal lymph nodes

N3 Mets to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or suprclavicular lymph nodes

M0 No distant mets

M1 Distant mets present (including metastatic tumor nodule in ipsilateral non-primary tumor lobe of the lung)

TNM Staging

Grouping TNM stagingStage 0 Tis N0 M0Stage IA T1 N0 M0Stage IB T2 N0 M0Stage IIA T1 N1 M0Stage IIB T2 N1 M0

T3 N0 M0Stage IIIA T1 N2 M0

T2 N2 M0T3 N1 M0T3 N2 M0

Stage IIIB Any T N3 M0T4 Any N M0

Stage IV Any T Any N M1

N2 nodes:

1-4

Regional nodes:

5-9

N1 nodes:

10-14

Risk Assessment

• Comorbidities might prohibit surgical resection

• Age alone is not a contraindication to surgery

• Preop cardiovascular risk assessment is needed

• Preop spirometry, FEV1, DLCO, ABG, quantitative perfusion scanning, formal or informal exercise testing

Treatment of NSCLC

• Stages I/II – definitive staging & pulmonary resection with negative margins

• Enbloc resection is adjacent structures are involved • Peripheral tumors can be taken with non-anatomic

wedge resection – higher risk for locoregional recurrence (25-50%)

• Central tumors should be treated with sleeve lobectomy rather than pneumonectomy when possible

• Nodal status should be confirmed – systematic sampling vs nodal dissection

Survival Rates of NSCLC

• Staging• Histology – needs to

be further defined • Squamous has

better survival than non-squamous cancer

• Does not seem to influence survival in late stage tumors

5-Yr Survival

Stage I – 60-70%

Stage II – 40-50%

Stage IIIA – 15-30%

Patterns of Recurrence

• Predominant sites of relapse for all stages after resection are distant mets

• For all stages, brain is single most common site of relapse

• Other common metastatic sites• Bone • Ipsilateral or contralateral lung • Liver • Adrenal glands

• 60% recurrences in 1st 2yrs after resection

• Virtually of recurrences related to primary tumor occur within 5yrs of resection

• Risk of new second cancer – 2-3% per year

• New, non-pulmonary cancer – breast, colon, prostate

Treatment of Stage III Disease

• Is locoregionally advanced disease • Stage IIIB considered unresectable

• T4 or N3 disease has no role for resection

• Small series have shown resection with invasion of SVC, left atrium, or aorta after induction chemo to downsize has survival benefit

• Stage IIIA treatment is controversial & complex

Treatment of Stage IIIA

Stage IIIA

T1 N2 M0

T2 N2 M0

T3 N1 M0

T3 N2 M0

5yr survival for N2 disease is 0-40%, usually 20-30% Varies with mediastinal

nodal involvement, size of primary tumor, & ability to achieve complete resection

Evidence suggests survival benefit for pts receiving preop chemo

Stage IIIA Neoadjuvant Therapy

• Optimal treatment not yet fully defined • Improved resectability & survival with

induction chemo vs resection or radiation alone

• Higher doses of radiation (>5500 cGy) are associated with postoperative ARDS and bronchial stump leak

Superior Sulcus Tumors

• Pancoast tumors• Previously thought to be uniformly fatal• Frequently involve: brachial plexus,

subclavian vessels, spine • Usually T3 or T4 (Stage IIIA or IIIIB)• Patients without N2 disease should have

induction chemoradiation followed by resection

Neuroendocrine Tumors

• Carcinoid• Atypical carcinoid• Small cell • Large cell

Typical & Atypical Carcinoid Tumors

• Low-grade malignant potential • About 2% of lung cancers• From neuroendocrine stem cells of

bronchial epithelium • Atypical carcinoids

• Increased mitotic activity• Increased nuclear pleomorphism • Areas of disorganization of architecture

& tumor necrosis

Carcinoid Tumors

• Presentation• Hemoptysis• Dyspnea• Recurrent/persistent pneumonitis

• Diagnosis• Bronchoscopy • CXR

• Carcinoid syndrome – only about 2%, usually in pts with liver mets

• Common sites of mets: lung, bone, liver, adrenals, brain

Carcinoid Tumors

• Treatment is surgical resection • Even in presence of nodal involvement • Should include mediastinal lymph node sampling or

dissection • Lobectomy needed in 50% • Endoscopic resection is associated with local

recurrence – should only be palliative • Long term surival >90% after resection in typical

carcinoid, 5yr survival after resection in atypical carcinoid 60%

• Recurrence more frequent in tumors >3cm with lymph node mets

Large Cell Neuroendocrine Carcinoma

• Microscopoicly similar to neuroendocrine tumors

• Tumors are large, have high mitotic rate, frequently have necrosis

• High-grade tumors• Related to smoking • Survival w/resection: 5yr 267%, 10yr 9%• Management similar to NSCLC

Small Cell Lung Cancer

• Most aggressive clinical course• Often widely disseminated at diagnosis• Responsive to chemotherapy • Limited disease = confined to one hemithorax and

regional lymph nodes, ipsilateral pleural effusion (positive or negative cytology)

• Distant mets: bone, liver, bone marrow, CNS• <10% SCLC is referred for surgical evaluation

Small Cell Lung Cancer

• Response to chemoradiation• Limited disease – 85-90%• Extensive disease – 75-85%• Chemo = cisplatin, etoposide

• 2yr survival remains poor• Role for resection in T1-2, N0-1 disease

• Adjuvant chemo usually given• Relapse at primary site uncommon after

resection

Bronchial Gland Carcinomas

• About 1% of all lung neoplasms

• Also called primary salivary gland-type tumors or bronchial adenomas

• Centrally located tumors present with irritation, cough, SOB, hemoptysis, recurrent infection, wheezing, stridor

• Smoking not a risk factor

• Most don’t metastasize

• Treatment is complete excision, preservin as much pulmonary tissue as possible

Adenoid Cystic Carcinoma

• Slow growing malignant tumor arising from submucosal glands of the trachea & main bronchi

• Tend to spread in the submucosal plane along the lymphatics

• Treat of choice is total resection • Postoperative radiation is given • Palliative treatment is endoscopic laser

removal & radiation

Mucoepidermoid Carcinoma

• Low or high-grade malignancy

• Have same microscopic appearance as the salivary gland tumor

• Present as submucosal lesions

• Treatment is similar to carcinoid

• High-grade tumors have the same prognosis as bronchogenic carcinoma

• Complete surgical resection is the mainstay of treatment

Mucous Gland Adenoma

• Rare, submucosal tumors arising from mucous glands

• Also known as bronchial cysts or papillary cystadenomas

• Benign tumor behavior

• Treated with endoscopic excision

• Surgical resection if endoscopic excision is contraindicated or incomplete or if distal lung is damaged by chronic infection

Surgical Resection of Pulmonary Metastases

• First reported in 1926• Historically done in pts w/complete resection of

primary tumor, no evidence of recurrence or other metastatic disease, & general good health

• Indications for resection of metastases have become more liberal

Clinical Presentation & Diagnosis

• Asymptomatic in 85%• CXR – well-circumscribed spherical, solid mass with well-

defined borders• Usually arise from parenchyma

• Endobronchial mets from renal cell, colon, breast• Hilar or mediastinal nodal involvement with pulmonary mets

– poor prognostic indicator • Solitary lesion: metastatic or new primary?

• More likely to be metastatic if primary lesion is sarcoma or melanoma

• More likely new primary if original tumor was head & neck or breast

Criteria for Surgical Resection

• Disease-free interval – time from resection of primary tumor to diagnosis of mestastases

• Tumor doubling time – measure of aggressiveness of tumor growth

• Number of metastatic nodules – considered predictive of survival

• Resection should only be undertaken if complete resection is considered feasible

• Not every metastatic lesion should be resected – some nodules indicate disseminated disease even if pulmonary nodule is solitary (breast)

Metastatectomy & Primary Disease/Recurrence

• Metastatic lesion & recurrence at primary site • Resect recurrent primary first

• Primary tumor & metastatic disease diagnosed simultaneously • Resect metastatic disease first if

primary tumor might not be completely resectable

Preoperative Evaluation

• Similar to that for pulmonary resection for primary cancer

• Pulmonary function post-chemotherapy may be substantially reduced • Bleomycin & mitomycin diminish DLCO & cause

ARDS-like picture postop (prevent by using <35% FiO2 intraop)

• Preop cardiac evaluation necessary, especially in pts receiving doxorubicin

• Avoid surgery while pt is neutropenic or thrombocytopenic

Surgical Technique

• Two priniciples:• Complete resection of disease • Maximal sparing of functioning lung tissue

• Anterolateral or posterolateral thoracotomy for unilateral disease

• Bilateral disease should be resected simultaneously if possible • Median sternotomy or clamshell incision

• VATS doesn’t allow palpation of lung – its role is questioned in resection of metastatic disease

• Repeat metastatectomy for recurrent disease is beneficial

Results

Primary Cancer 5-Year Survival

Renal Cell 54%

Head & Neck Cancer• Squamous cell• Glandular tumors• Overall

34%64%50%

Colorectal Cancer 44%

Soft Tissue Sarcoma• Incomplete resection • No resection • Unknown • Overall

46%23%17%25%

Testicular Germ Cell Tumors 68%

Benign Tumors of the Lung

Epithelial Mesen-chymal Muscle Misc Other Inflam-matory

Polyps Sclerosing hemangioma

Leiomyoma Hamartoma Lipoma Plasma cell granuloma

Papilloma Lymphagioma Teratoma Chondroma Pulmonary hyalinizing granuloma

Mucous gland adenoma

Granular cell tumor

Clear cell tumor

Fibroma

Neurilemoma

Neurofibroma

Hamartoma

• Most frequent benign tumor • 75% of benign lesions

• Most frequent component is cartilage• Extremely slow growth • Do not require excision unless centrally

located & cause symptoms of obstruction, etc or carcinoma can’t be ruled out

Other Benign Tumors

• May present as endobronchial lesions• May be removed endoscopically • Surgical excision when diagnosis is in

doubt or when endoscopic excision has been incomplete

• Peripheral tumors are often removed for diagnosis