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Non-small cell lung cancer

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    Lung Cancer

Surgery is indicated for clinically staged IA, IB, IIA, and IIB NSCLC. A multimodality
approach is recommended for stage IIIA and IIIB disease, while systemic and palliative therapy is indicated in stage IV disease.

Stages I and II

Surgery is indicated for clinically staged IA, IB, IIA, and IIB NSCLC. Preoperative assessment should include histologic evaluation of mediastinal disease. These patients should not be treated surgically.

1. Surgery

Procedures include:

  • Resection of the lobe containing the tumor.
  • Bilobectomy or pneumonectomy may be required.
  • A wedge or segmental resection for has a 3-5 times higher incidence of local recurrence and a lower 5-year.

Traditionally, lung cancers have been resected through a posterolateral thoracotomy incision. Many surgeons have switched to a muscle-sparing incision, because studies have shown that this approach reduces pain. Currently, the trend is toward an even less invasive approach: lobectomy and lymph node dissection with Video assisted thoracoscopic surgery (VATS). It appears that this approach offers the same cancer operation and survival is reported to have lower morbidity and mortality.

The standard lung cancer operation should include sampling or dissection of mediastinal lymph nodes. The presence of metastases in any of the mediastinal lymph nodes (N2 disease) has prognostic significance.

Mortality: Mortality following lobectomy and pneumonectomy approximates 3% and 7%, respectively.

Benefits: Patients with pathologic stage IA disease have an 80% 5-year survival rate after resection, whereas 5-year survival rates are 60% in those with stage IB disease and 40%-50% in those with stage IIA/IIB disease. Patients found to have N2 (stage IIIA) disease located at a single nodal level have a 25%-30% 5-year survival rate.

2. Adjuvant radiation therapy


The role of postoperative radiation therapy remains controversial. However, it should be seriously considered in patients at high risk for locoregional relapse:

  • Squamous pathology

  • Patients with N2 disease

  • Multiple positive lymph nodes

  • Extracapsular extension

  • Close or microscopically positive margins


  • In patients with resected N1/N2 disease postoperative radiation reduced the risk of recurrence in the chest from 20% to 1%.

  • There was significant improvement in disease-free survival but no improvement in overall survival in these patients.

3. Adjuvant chemotherapy

The value of adjuvant chemotherapy for resectable NSCLC has been debated.

Main trials

  • The ALPI (Adjuvant Lung Project Italy) study of 1,209 patients also showed no survival benefit.
  • The International Adjuvant Lung Cancer Trial cisplatin-based adjuvant chemotherapy had a survival advantage of 4.1% at 5 years (P = .003).

  • The adjuvant UFT trial in patients with stage Ib NSCLC showed a survival advantage.

There is less evidence to date supporting carboplatin-based adjuvant therapy than cisplatin-based adjuvant therapy. The choice of the second agent with cisplatin remains open to debate.

4. Radiation therapy


Some patients with resectable stage I or II NSCLC are high-risk operative candidates because of poor cardiopulmonary function, other medical problems, or advanced age. Other patients refuse to undergo surgery despite the recommendation of their treating physicians. In such patients, an attempt should be made to optimize pulmonary function by encouraging smoking cessation and initiating vigorous treatment with bronchodilators, corticosteroids, and antibiotics.

Although the results are not as good as those reported in patients selected for surgery (possibly due to differences in patient selection and between clinical vs pathologic staging), patients with medically inoperable early-stage NSCLC clearly should be offered radiation therapy, with reasonable expectation of cure. Timmerman et al reported the results of a phase I study of extracranial stereotactic radioablation (ESR) in patients with medically inoperable stage I NSCLC. ESR was delivered in 3 fractions over 2 weeks, with a starting dose of 800 cGy per fraction. The dose was escalated to 2,000 cGy per fraction for 3 fractions (6,000 cGy total). Of 36 patients, 1 developed grade 3 hypoxemia and another symptomatic radiation pneumonitis. The maximum tolerated dose was not reached.

Radiofrequency ablation

Patients who are not operative candidates can also be treated with radiofrequency ablation (RFA). There is considerable experience with RFA for cancer in other organs, and its use for lung cancer is growing. It can be performed either intraoperatively or percutaneously with CT guidance. The preliminary findings show these radiologic results: complete response (0%), partial response (50%), stable disease (30%), and disease progression (20%).

Stage III



The greater effectiveness of current chemotherapeutic regimens in settings of reduced disease bulk suggested that their use prior to surgery, either alone or in combination with radiation therapy, might increase both resectability and survival in patients with stage IIIA or IIIB NSCLC.

Recently, an intergroup trial demonstrated an impressive 50% pathologic complete response rate and a 50% 3-year survival rate with preoperative chemotherapy (cisplatin/etoposide) administered concurrently with irradiation (45 Gy) to patients with T3-T4 N0 M0 Pancoast tumors.

treatment-associated mortality in the range of 5%-12%,



At present, it is reasonable to consider concurrent chemoradiation therapy (with once- daily radiation therapy) as a new treatment paradigm in stage III (inoperable) lung cancer patients with an ECOG performance status of 0/1 who have not lost more than 5% of their usual body weight.


  • Daily cisplatin/radiotherapy had a 16% 3-year survival rate vs 2% for radiotherapy alone while weekly cisplatin/radiotherapy produced 13% 3-year survival (EORTC - trial 08844).
  • Weekly carboplatin-etoposide combined with hyper-fractionated radiotherapy produced a 23% 3-year survival vs. 7% for hyper-fractionated radiotherapy alone and  16% 3-year survival for those who received hyper-fractionated radiotherapy with carboplatin-etoposide given every other week (P = 0.003).

Stage IV

1st generation cisplatin-containing regimens

Older regimens such as cisplatin/etoposide showed only a modest effect on survival, improving median survival by approximately 6 weeks, according to a meta-analysis, and yielding a 1-year survival rate of approximately 20% (as compared with a rate of approximately 10% for supportive care).

New regimens

However, several new chemotherapeutic agents have produced response rates in excess of 20% in NSCLC. The potentially useful new agents include the taxanes (paclitaxel and docetaxel), vinorelbine, gemcitabine, and irinotecan.

Furthermore, randomized trials demonstrated that a new agent plus cisplatin combination significantly improves the response rate over cisplatin monotherapy (historically considered the most active agent for NSCLC). This increase in response rates translates into significant, although modest, improvement in survival outcome for patients receiving vinorelbine, gemcitabine.

There is no survival advantage for one regimen over another or standard regimen vs regimens containing newer agents.

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