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Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. Refer to the PDQ levels of evidence summary for more information. T1, N2, M0 or T2, N2, M0 or T3, N1, M0 or T3, N2, M0 Depending on clinical circumstances, the principal forms of treatment that are considered for patients with stage III non-small cell lung cancer (NSCLC) are radiation therapy, chemotherapy, surgery, and combinations of these modalities. Although the majority of these patients do not achieve a complete response to radiation therapy, there is a reproducible long-term survival benefit in 5% to 10% of patients treated with standard fractionation to 6,000 cGy, and significant palliation often results. Patients with excellent performance status and those who require a thoracotomy to prove that surgically unresectable tumor is present are most likely to benefit from radiation therapy.[1] Because of the poor long-term results, these patients should be considered for clinical trials. Trials examining fractionation schedules, endobronchial laser therapy, brachytherapy, and combined modality approaches may lead to improvement in the control of this regional disease.[2] One prospective randomized clinical study showed that radiation therapy given as 3 daily fractions improved overall survival compared to radiation therapy given as 1 daily fraction.[3][Level of evidence: 1iiA] The addition of chemotherapy to radiation therapy has been reported to improve survival in prospective clinical studies that have used modern cisplatin-based chemotherapy regimens.[4-7] A meta-analysis of patient data from 11 randomized clinical trials showed that cisplatin-based combinations plus radiation therapy resulted in 10% reduction in the risk of death compared with radiation therapy alone.[8] The optimal sequencing of modalities and schedule of drug administration remains to be determined and is under study in ongoing clinical trials.[9] Patients with N2 disease apparent on chest radiograph and documented by biopsy or discovered by prethoracotomy exploration have a 5-year survival rate of only about 2%. The use of preoperative (neoadjuvant) chemotherapy has been shown to be effective in these clinical situations in 2 small randomized studies of a total of 120 patients with stage IIIa NSCLC.[10,11] The 58 patients randomized to 3 cycles of cisplatin-based chemotherapy followed by surgery had a median survival more than 3 times as long as patients treated with surgery but no chemotherapy in both these studies. Two additional single-arm studies have evaluated either 2 to 4 cycles of combination chemotherapy or combination chemotherapy plus chest irradiation for 211 patients with histologically confirmed N2 stage IIIa NSCLC.[12] Sixty-five percent to 75% of patients were able to have a resection of their cancer, and 27% to 28% were alive at 3 years. These results are encouraging, and combined-modality therapy with neoadjuvant chemotherapy with surgery and/or chest radiation therapy should be considered for patients with good performance status who have stage IIIa NSCLC. Although most retrospective studies suggest that postoperative radiation therapy can improve local control for node-positive patients whose tumors were resected, it remains controversial whether it can improve survival.[13,14] One controlled trial in patients with completely resected stage II or III squamous cell lung cancer failed to demonstrate a survival benefit for patients who received postoperative irradiation, although local recurrences were significantly reduced.[15] A meta-analysis of 9 randomized trials evaluating postoperative radiation versus surgery alone showed no difference in overall survival with adjuvant radiation in patients with stage III disease.[16][Level of evidence: 1iiA] It will be important to determine whether these outcomes can potentially be modified with technical improvements, better definitions of target volumes, and limitation of cardiac volume in the radiation portals. In 2 controlled trials with carefully staged surgically resected patients, adjuvant combination chemotherapy with cisplatin, doxorubicin, and cyclophosphamide produced modestly increased disease-free survival and a trend toward improved survival, especially in the first year after surgery.[17-19] Based on these data, participation in clinical trials evaluating adjuvant therapy after surgical resection should be encouraged. No consistent benefit from any form of immunotherapy has been demonstrated thus far in the treatment of NSCLC. Treatment options:
Another category that merits a special approach is that of superior sulcus tumors, a locally invasive problem usually with a reduced tendency for distant metastases. Consequently, local therapy has curative potential, especially for T3, N0 disease. Radiation therapy alone, radiation therapy preceded or followed by surgery, or surgery alone (in highly selected cases) may be curative in some patients, with a 5-year survival rate of 20% or more in some studies.[23] Patients with more invasive tumors of this area, or true Pancoast tumors, have a worse prognosis and generally do not benefit from primary surgical management. Follow-up surgery may be used to verify complete response in the radiation therapy field and to resect necrotic tissue. Treatment options:
Selected patients with bulky primary tumors that directly invade the chest wall can obtain long-term survival with surgical management provided that their tumor is completely resected. Treatment options:
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