See also "Pulmonary Nodules"

I. Histologic subtypes

  1. Squamous cell (epidermoid)
  1. 30-35% of lung Ca's; most common type in men; incidence is decreasing
  2. Us. centrally located
  3. Best prognosis (35-50% 5yr survival)
  1. Adenocarcinoma
  1. 40% of cases; most common type in women
  2. Us. peripherally located
  3. Worst prognosis: slow growing (6mo doubling time) but metastasizes early
  4. Most common lung cancer in nonsmokers
  1. Small Cell ("Oat Cell")
  1. 25% of cases
  2. Rapid growth
  3. 3 cell types: lymphocyte-like, spindle cell, and polysomal cell
  4. Followup surveillance for small-cell lung Ca: one f/u study of 115 pts who had small-cell and achieved initial remission but subsequently had recurrence found that most common site of recurrence was lung or pleura (44%), followed by lymph nodes (30%), liver (26%), and brain (22%). 18% of these pts had no abnormalities on Hx or Px at time of recurrence; recurrence was identified by CXR and blood studies in these pts.
  1. Undifferentiated (large cell)
  1. 10% of cases
  2. Two types: "giant cell" and "clear cell"

II. Screening

  1. Screening trials using CXR have failed to show a significant mortality reduction (Lancet 354:86, 1999 cited in Med. Lett. 43:61, 2001)
  2. Screening with CT
    1. 1000 asymptomatic but "high-risk" pts (> 60yo, fit to undergo thoracic surgery, no previou sCa hx, at least 10 pack-year smoking hx) underwent low-dose chest CT and CXR; CT identified 27 cases of lung Ca; only 7 of these were detected by CXR ("Early Lung Cancer Action Project," Lancet 354:99, 1999--JW)
    2. 1611 asymptomatic smokers underwent spiral CT, CXR, and sputum cytology; CT's were repeated Q6mos if abnormal.  Overall, 36 pts were dx'd with lung Ca; 32 of these by CT (J. Clin. Oncol. 20:911, 2002--JW)
    3. 1520 smokers received spiral CT + sputum cytology Q1y x 2; 25 lung Ca's were dx'd, 23 by CT; 7 pts underwent lung resections for benign lesions (Am. J. Resp. Crit. Care Med. 165:508, 2002--JW)
    4. In an uncontrolled study of annual spiral CT for lung Ca screening in pts with h/o smoking or occupational exposure to lung carcinogens, over median 40mo f/u, 85% of detected cancers were stage I.  ("International Early Lung Cancer Action Program" ("I-ELCAP"); NEJM 355:1763, 2006--JW)
  3. 9211 male smokers randomized to CXR + sputum cytology Q4mo x 6y vs. no screening; over median f/u of 20.5y; no sig. diff. in lung Ca deaths between the groups (J. Nat. Cancer Inst. 92:1308, 2000--JW)

III. Staging

  1. Of great importance in many cases of non-small-cell lung Ca, since more accurate staging reduces risk of unnecessary surgical resection (i.e. can increase the detection rate of metastatic disease
  2. Modalities
    1. Standard imaging procedures (CT, MR, etc.)
    2. PET imaging
      1. PET scanning to select pts for surgery (among patient suspected of having non-small-cell lung Ca) was associated with lower risk of futile surgery (where ultimately dx'd with unresectable Ca or benign disease) in one randomized trial (Lancet 359:1388, 2002--JW)
    3. Mediastinoscopy (for tissue sampling of mediastinal lymph nodes)
    4. Transbronchial fine-needle aspiration (via bronchoscopy)
    5. Transesophageal ultrasound-guided fine-needle aspiration (for tissue sampling of paraesophageal lymph nodes (see JAMA 294:931, 2005--abst)

IV. Treatment

  1. For purposes of treatment, usually divided into small cell and "non small cell" (squamous cell and adenocarcinoma)
  2. Small cell usually treated with chemo and radiation; responds in 75-90% of cases; surgical treatment may increase survival in stage I pts, but few are diagnosed at stage I
  3. Inoperable lung Ca (primary or metastatic) can be palliated with radiation; can be delivered from outside ("external-beam") or via bronchoscopy (endobronchial brachytherapy), the latter to address obstruction of the central airways (trachea or bronchi).  Endobronchial brachytherapy and/or ablative procedures can be followed by stenting to maintain airway patency.
  4. Non-small-cell lung Ca
  1. Surgical resection
    1. How much to take out (wedge resection vs. lobectomy vs. pneumonectomy) based on assessment of pulmonary reserve (the more there is, the more they take out) and on extent of tumor
  2. Radiation (XRT) sometimes used preoperatively or as palliation
    1. Radiation postoperatively after complete resection ass'd with RR of death of 1.21 (worse in stage I or II than in stage III disease) in a meta-analysis involving 2,128 pts from 9 trials (Lancet 352:257, 1998--JW)
    2. In a randomized trial in 230 pts with unresectable non-small-cell lung Ca but no chest-related sx randomized to immediate XRT vs. XRT if/when sx attributable to Ca occurred, symptoms-free survival at 6mos was no different in the two groups (28% vs. 26%, respectively) (BMJ 325:465, 2002--JW)
  3. Chemotherapy for non-small-cell lung Ca
    1. One randomized study of 488 pts with stage II or IIIa non-small-cell lung Ca randomized to XRT + chemo (cisplatin + etoposide) vs. XRT + placebo showed no diff. in survival over median 44mo f/u (NEJM 343:1217, 2000--JW)
    2. 1900 pts with non-small-cell lung Ca stage I-III s/p complete surgical resection randomized to post-op chemotherapy (cisplatin + one other drug, usually etoposide or vinorelbine) vs. no chemo. Chemo recipients had sig. higher 5y survival (44.5% vs. 40.4%) and 5y disease-free survival (39.4% vs. 34.3%) (NEJM 350:351, 2004--JW)
    3. In a study of 979 pts with stage I adenocarcinoma of the lung s/p complete surgical resection randomized to Uracil-Tegafur (an oral chemotherapeutic agent) vs. placebo x 2y, active-tx group had sig. higher 5y survival (88% vs. 85%); on subgroup analysis, survival advantage was limited to pts with T2 disease (NEJM 350:1713, 2004--AFP)
    4. In a study of 482 with completely resected stage IB or II non-small-cell lung Ca randomized to chemo (vinorelbine + cisplatin) vs. observation; over median 5y f/u, chemo group had sig. greater 5y survival (69% vs. 54%) (NEJM 352:2589, 2005--JW)
  4. In a study of 458 pts with unresectable non-small-cell lung Ca but w/o mets randomized to standard XRT, chemo (cisplatin + vinblastine) + XRT, or hyperfractionated (BID) XRT, 5y survival was sig. higher in the combined group (8% vs. 5% and 6%, respectively); for pts > 70yo, standard XRT was ass'd with the highest survival (Chest 117:374, 2000--JW)
  5. Epidermal growth factor inhibitors
    1. Erlotinib, an EGF inhibitor, was shown to sig. increase survival c/w placebo in a study of 731 pts with stage IIIB or IV non-small-cell lung Ca unresponsive to prior chemotherapy (NEJM 353:123, 2005--JW) 

(Source: Mont Reid Surgical Handbook, 2nd ed., 1990 and other sources as noted)