Broad Categories of Lung Cancer ClassificationsNSCLC (Non-Small Cell Lung Cancer) (80%) most common histologic subtypes

adenocarcinoma and squamous cell

adenocarcinoma is most common overall, and in nonsmokers squamous cell is usually more central (closer proximity to lung hilum) and in smokers other histologic

subtypes are ; large cell and Bronchoalveolar carcinoma (BAC)

SCLC (Small Cell Lung Cancer) SCLC divided into;

limited stage (LS) (in chest only) and extensive stage (ES) (when there are contralateral supraclavicular nodes or distant disease).

characterized by rapid growth and frequent extrathoracic metastasis microscopically cells contain neurosecretory granules almost all cases in patients with smoking history

Low grade tumors Carcinoid tumors,‘typical’(or ‘mature’) Mucoepidermoid tumors Adenoid cystic tumors all arise in tracheobronchial tree (except occasionally typical carcinoid)

Other unusual tumors Bronchioalveolar carcinoma (BAC)

palisading cells that spread along alveolar membrane better prognosis than NSCLC recur within lung parenchyma, less frequent lymph node involvemt or distant metastasis

Atypical carcinoids worse prognosis than typical carcinoid tumors (more freq +LN, distant mets) but better

than NSCLC behave almost as aggressively as SCLC

Clinical Presentation: median age NSCLC presentation 65-70 90% are symptomatic 60-80% of patients with NSCLC have stage III or IV disease at presentation 2/3 of NSCLC are in the upper lobes equally distributed central and peripheral, regardless of histology

Evaluation/Diagnosis:

Patients evaluated by a surgeon in the MTOP clinic are often referred with a chest xray or CT finding suspicious for lung CA.

The general algorithm for evaluation of these patients is as follows: 1) Begin with talking to the patient.

Assess risk factors for lung CA and symptoms. Evaluate for both organ-specific lung symptoms as well as neurologic findings or bone pain, as well as constitutional symptoms – fever, fatigue, anorexia, weight loss, night sweats. The time period over which symptoms have developed is important, and examine the patient.

2) Review available films. Assess the interval change in the lesion (if previous films are available), and radiographic features of the abnormality- smooth borders, spiculated lesion, indistinct borders, size, location, presence of abnormal (>1cm) mediastinal lymph nodes (N2, N3).A spiculated lesion has an approximate 80% chance of being CA, lobulated lesion 60%, and indistinct borders usually indicate an inflammatory process.

→With all of the above information, you should be able to have some idea of the following three things which influence significantly the plans for the rest of the workup and treatment:

whether the patient likely has lung cancer a leaning toward NSCLC vs. SCLC (time period and aggressiveness indicate this) whether the patient likely has early stage or advanced stage lung CA

3) If you think the patient has early stage (I or II) NSCLC, then he/she may be a candidate for an

operation. In stage I and II patients, the clinical evaluation is pretty good for ruling out systemic disease (false negative rate 5%). So these patients usually need intrathoracic staging only, by either CT scan, PET scan and/or mediastinoscopy (or a combination, depending on the overall clinical scenario), to rule out mediastinal disease (N2 nodes) which would make them stage III.

CT guides suspicion of mediastinal adenopathy (where >1cm=abnormal LN) but: CT carries a 40% false positive rate for mediastinal lymphadenopathy for central tumors, there is a 20-25% false negative rate CT lymph node findings should be pathologically confirmed by mediastinoscopy, CT-FNA, bronch-

guided Wang needle, EUS-FNA

Whether the lesion is‘central’ or ‘peripheral’ on CT scan plays a role in intrathoracic staging. For peripheral tumors, the FN rate of CT is low enough that if the CT does not show mediastinal

nodes >1cm, this does not need to be confirmed by mediastinal lymph node biopsy. For central tumors, CT scan may have a FN rate as high as 25% for mediastinal lymph node

involvement, requiring confirmation by mediastinoscopy, or needle aspiration by EUS or bronchoscopy.

Positive N2 and N3 nodes on CT scan must also be confirmed by biopsy, due to a high false positive rate (40%).

A histologic diagnosis of CA is not always obtained in early stage NSCLC patients until the time of resection, unless it is obtained at the time of mediastinal staging.

Patients who are confirmed to have stage I or II NSCLC will be evaluated for surgical resection. After the determination is made that the tumor is resectable, the patient’s performance status

(PS) (Table 5 below) and pulmonary function tests (PFTs) play a major role in whether the patient undergoes surgery.

Evaluation for surgery: Determination of postoperative FEV1 (ppo FEV1): if <0.8L or <40% predicted there is an

associated increased perioperative mortality (applicable to open lobectomy only, not VATS lobe, segmentectomy)

If you think the patient potentially has advanced stage lung cancer with systemic or distant disease, then they will need further imaging to rule this in or out- good data from multiple sources that clinical evaluation has ~30% false negative rate if the clinical stage is III or greater.

Extrathoracic staging usually involves a bone scan, a CT of the liver and adrenals, and a brain MRI or CT, and or PET scan.

If the patient has presumed small cell lung cancer, or signs and symptoms of advanced stage NSCLC, a tissue confirmation of the diagnosis is obtained prior to initiation of chemotherapy or radiation from the easiest site.

Needle aspiration of a superficial lymph node, or transthoracic FNA or thoracoscopic biopsy of the lesion, cytological analysis of sputum or pleural fluid, or biopsy of a presumed metastasis.

If imaging reveals a possible evidence of metastasis, diagnosis/staging by needle biopsy is done only if there appears to be only a solitary met, or if it has an atypical appearance, or if there is no tissue diagnosis already available.

If it reveals the typical presentation and radiographic appearance of multiple mets then that is accepted by virtually everyone without further testing.

Treatment/Outcomes: SCLC: Primary treatment:

LS= chemoRT (concurrent, early RT) ES=chemotherapy

Untreated median surv: LS=12 wks ES=5-8 wks

Complete tumor response to chemo (CR) seen in 50-75% in pts w/ limited disease, but 5yr overall

survival still 15-20% XRT is done for local tumor control ●Prophylactic Cranial Irradiation (PCI)-

given to pts w/ complete response(CR) to chemo since brain mets known to develop in 80% of SCLC patient.

about 5% survival benefit w/ PCI

NSCLC: If untreated the median survival is 6 months Treatment by stage: Below are generalizations about accepted standard of care for NSCLC patients by stage. However, extent of treatment is influenced a great deal by the patient’s performance status. I and II: -Surgical resection

In summary, this includes patients with T1 or T2 tumors, a negative mediastinum and no known distant disease.

Exception to this is that T3N0 patients, who are node negative but have tumor involving chest wall, are also stage II and often resected.

Adjuvant chemotx has recently become the standard of care for completely resected, selected LN negative pts after resection for NSCLC.

This has been shown to lead to an absolute 5 year survival benefit of 4% over surgery alone.

Surgical resection (Stage I and II disease) pneumonectomy- higher mortality rate 9% -pneumonia/respiratory failure, MI, empyema

most common causes lobectomy- standard cancer resection, mortality rate 3% -‘sleeve’ lobectomies (removal of

a section of airway or artery with reanastomosis of proximal and distal segments) are often done to avoid pneumonectomy

non-anatomic resections (segmentectomy, wedge, lumpectectomy) are associated with increased local recurrence and decreased survival = not standard of care for a lung cancer resection.

5yr survival rates in surgically resected NSCLC pts: stage I 60-70% stage II 40%

This survival data is based on patients who had ‘R0’ (complete) resections Recurrence occurs in 33-50% of resected stage I and II NSCLC patients.

The majority of recurrences are in distant sites.

III and IV: Standard treatment for stage III and stage IV disease=chemotherapy and radiotherapy But, some IIIa patients may undergo surgical resection if they are clinically staged preop as stage II. 5-yr post resection survival for stage IIIa patients who are discovered to have stage IIIa disease at the

time of resection is 25%.