Surgery is indicated for clinically staged IA, IB, IIA, and IIB
NSCLC. A multimodality
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.
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:
3. Adjuvant chemotherapy
The value of adjuvant chemotherapy for resectable NSCLC has been debated.
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.
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%).
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.
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).
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.