Non-Small Cell Lung Cancer Professional Information

STAGE I NON-SMALL CELL LUNG CANCER

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, N0, M0 or T2, N0, M0

Surgery is the treatment of choice for patients with stage I non-small cell lung cancer (NSCLC). Careful preoperative assessment of the patient's overall medical condition, especially the patient's pulmonary reserve, is critical in considering the benefits of surgery. The immediate postoperative mortality rate is age-related, but 3% to 5% with lobectomy can be expected.[1] Patients with impaired pulmonary function may be considered for segmental or wedge resection of the primary tumor; the Lung Cancer Study Group has conducted a randomized study (LCSG-821) to compare lobectomy with limited resection for patients with stage I cancer of the lung. The results of this study show a reduction in local recurrence for patients treated with lobectomy compared with those treated with limited excision but no significant difference in overall survival.[2] Similar results have been reported from a nonrandomized comparison of anatomic segmentectomy and lobectomy.[3] A survival advantage was noted with lobectomy for patients with tumors greater than 3 centimeters, but not for those with tumors smaller than 3 centimeters. However, the rate of local/regional recurrence was significantly less after lobectomy, regardless of primary tumor size. Another study of stage I patients showed that those treated with wedge or segment resections had a local recurrence rate of 50% (31 of 62) despite having undergone complete resections.[4] Exercise testing may aid in the selection of patients with impaired pulmonary function who can tolerate lung resection.[5] The availability of video-assisted thoracoscopic wedge resection permits limited resections in patients with poor pulmonary function who are not usually considered candidates for lobectomy.[6]

Inoperable patients with stage I disease and with sufficient pulmonary reserve may be considered for radiation therapy with curative intent. In a single report of patients older than 70 years of age who had resectable lesions smaller than 4 centimeters but who were medically inoperable or who refused surgery, survival at 5 years following radiation therapy with curative intent was comparable to a historical control group of patients of similar age resected with curative intent.[7] In the 2 largest retrospective radiation therapy series, inoperable patients treated with definitive radiation therapy achieved 5-year survival rates of 10% and 27%. Both series found that patients with T1, N0 tumors had better outcomes, with 5-year survival rates of 60% and 32% in this subgroup.[8,9]

Primary radiation therapy should consist of approximately 6,000 cGy delivered with megavoltage equipment to the midplane of the known tumor volume using conventional fractionation. A boost to the cone-down field of the primary tumor is frequently used to further enhance local control. Careful treatment planning with precise definition of target volume and avoidance of critical normal structures to the extent possible is needed for optimal results and requires the use of a simulator.

Many patients treated surgically subsequently develop regional or distant metastases.[10] Therefore, patients should be considered for entry into clinical trials evaluating adjuvant treatment with chemotherapy or radiation therapy following surgery. A meta-analysis of 9 randomized trials evaluating postoperative radiation versus surgery alone showed a 7% reduction in overall survival with adjuvant radiation in patients with stage I or II disease.[11][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. Trials of adjuvant chemotherapy regimens have failed to demonstrate a consistent benefit. Smokers who undergo complete resection of stage I NSCLC are also at risk for second malignant tumors. In the Lung Cancer Study Group trial of 907 stage T1, N0 resected patients, the rate of nonpulmonary second cancers was 1.8% per year and 1.6% per year for new lung cancers.[12] Others have reported even higher risks of second tumors in long-term survivors, including rates of 10% for second lung cancers and 20% for all second cancers.[4] A randomized trial of vitamin A versus observation in resected stage I patients showed a trend toward decreased second primary cancers in the vitamin A arm with no difference in overall survival rates.[13] An ongoing intergroup clinical trial will evaluate the role of isotretinoin in the chemoprevention of second cancers in patients resected for stage I NSCLC.[14]

Treatment options:

1. Lobectomy or segmental, wedge, or sleeve resection as appropriate.

2. Radiation therapy with curative intent (for potentially resectable patients who have medical contraindications to surgery).

3. Clinical trials of adjuvant chemotherapy following resection.[15,16]

4. Adjuvant chemoprevention trials.[13,14]

5. Endoscopic photodynamic therapy (under clinical evaluation in highly selected T1, N0, M0 patients).[17]

1. Ginsberg RJ, Hill LD, Eagan RT, et al.: Modern thirty-day operative mortality for surgical resections in lung cancer. Journal of Thoracic and Cardiovascular Surgery 86(5): 654-658, 1983.
2. Ginsberg RJ, Rubinstein LV: Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Annals of Thoracic Surgery 60(5): 615-623, 1995.
3. Warren WH, Faber LP: Segmentectomy versus lobectomy in patients with stage I pulmonary carcinoma. Journal of Thoracic and Cardiovascular Surgery 107(4): 1087-1094, 1994.
4. Martini N, Bains MS, Burt ME, et al.: Incidence of local recurrence and second primary tumors in resected stage I lung cancer. Journal of Thoracic and Cardiovascular Surgery 109(1): 120-129, 1995.
5. Morice RC, Peters EJ, Ryan MB, et al.: Exercise testing in the evaluation of patients at high risk for complications from lung resection. Chest 101(2): 356-361, 1992.
6. Shennib HA, Landreneau R, Mulder DS, et al.: Video-assisted thoracoscopic wedge resection of T1 lung cancer in high-risk patients. Annals of Surgery 218(4): 555-560, 1993.
7. Noordijk EM, Clement EP, Hermans J, et al.: Radiotherapy as an alternative to surgery in elderly patients with resectable lung cancer. Radiotherapy and Oncology 13(2): 83-89, 1988.
8. Dosoretz DE, Katin MJ, Blitzer PH, et al.: Radiation therapy in the management of medically inoperable carcinoma of the lung: results and implications for future treatment strategies. International Journal of Radiation Oncology, Biology, Physics 24(1): 3-9, 1992.
9. Gauden S, Ramsay J, Tripcony L: The curative treatment by radiotherapy alone of stage I non-small cell carcinoma of the lung. Chest 108(5): 1278-1282, 1995.
10. Martini N, Bains MS, Burt ME, et al.: Incidence of local recurrence and second primary tumors in resected stage I lung cancer. Journal of Thoracic and Cardiovascular Surgery 109(1): 120-129, 1995.
11. PORT Meta-analysis Trialists Group: Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. Lancet 352(9124): 257-263, 1998.
12. Thomas P, Rubinstein L: Cancer recurrence after resection: T1 N0 non-small cell lung cancer: Lung Cancer Study Group. Annals of Thoracic Surgery 49(2): 242-246, 1990.
13. Pastorino U, Infante M, Maioli M, et al.: Adjuvant treatment of stage I lung cancer with high-dose vitamin A. Journal of Clinical Oncology 11(7): 1216-1222, 1993.
14. Lippman SM, University of Texas - MD Anderson Cancer Center: Phase III, Double-Blind, Randomized Trial of 13-CRA vs Placebo to Prevent Second Primary Tumors in Patients with Totally Resected Stage I non-Small Cell Lung Cancer (Summary Last Modified 07/97), MDA-ID-91025, clinical trial, closed, 04/09/1997.
15. Feld R, Rubinstein L, Thomas PA, et al.: Adjuvant chemotherapy with cyclophosphamide, doxorubicin, and cisplatin in patients with completely resected stage I non-small-cell lung cancer. Journal of the National Cancer Institute 85(4): 299-306, 1993.
16. Niiranen A, Niitamo-Korhonen S, Kouri M, et al.: Adjuvant chemotherapy after radical surgery for non-small-cell lung cancer: a randomized study. Journal of Clinical Oncology 10(12): 1927-1932, 1992.
17. Furuse K, Fukuoka M, Kato H, et al.: A prospective phase II study on photodynamic therapy with photofrin II for centrally located early-stage lung cancer. Journal of Clinical Oncology 11(10): 1852-1857, 1993.

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