CLINICAL-PRACTICE GUIDELINES FOR THE TREATMENT OF UNRESECTABLE NON-SMALL-CELL LUNG-CANCER

Purpose: The primary objective was to determine clinical practice guid elines for the diagnostic evaluation, treatment, and follow-up care of patients with surgically unresectable stage III and IV non-small-cell lung cancer (NSCLC). These guidelines are intended for use by oncolog ists in the care of patients outside of clinical trials. Methods: An e xpert multidisciplinary Panel reviewed pertinent information from the published literature through April 1997; certain investigators were co ntacted for more recent and, in some cases, unpublished information. A computerized search was performed of MEDLINE data; directed searches based on the bibliographies of primary articles were also performed. V alues for levels/grades of evidence were assigned by expert reviewers and approved by the Panel. Expert consensus was used for issues in whi ch published data were insufficient. The options considered included t he appropriate diagnostic evaluation of patients; the role of chemothe rapy, radiation, and surgery; and strategies for follow-up care and li festyle changes. The significant health outcomes considered in making the clinical practice guidelines included survival (disease-free and o verall), quality of life, toxicity (both short- and long-term), and co st-effectiveness. An intervention or strategy was assigned benefit if it led to favorable changes in the outcomes listed. Harms considered w ere inappropriate disease management and excess cost without definable benefit. Costs were considered but were never the sole determinant fo r a recommendation. The guidelines underwent external review by select ed physicians and a cancer quality-of-life expert, by Health Services Research Committee members, and by the American Society of Clinical On cology (ASCO) Board of Directors. Results and Conclusions: In patients without evidence of extrathoracic cancer, a chest x-ray and chest com puted axial tomography (CAT) scan are recommended to stage locoregiona l disease, with biopsy of mediastinal lymph nodes found on CAT scan to be greater than 1 cm in shortest transverse diameter. Pretreatment bo ne scan and head CAT scan are recommended only when signs or symptoms of disease are present. If a patient is otherwise potentially resectab le, a biopsy should be performed of a radiographically documented isol ated adrenal or hepatic mass to rule out metastatic disease. Chemother apy, ideally a platinum-based regimen, is appropriate for selected pat ients who have a good performance status with both unresectable, local ly advanced, and metastatic NSCLC. A detrimental effect on survival wa s observed with older alkylating agent-based regimens. In patients wit h unresectable stage III NSCLC, two or more cycles of cisplatin-based chemotherapy with or followed by radiation has been proven to enhance survival; ongoing maintenance chemotherapy is of unproven benefit. Che motherapy should be administered for no more than eight cycles in pati ents with stage III or IV NSCLC. Initial treatment with an investigati onal agent is appropriate, provided a standard regimen is then given i f the disease does not respond after two cycles. Delaying chemotherapy until symptoms develop may negate the survival benefits of treatment. There is no current evidence that either confirms or refutes that sec ond-line chemotherapy improves survival in patients with nonresponding or progressive NSCLC. NSCLC histologic type is not an important progn ostic factor in these patients, and the role of newer prognostic facto rs (eg, p53 mutation) in clinical decision-making is investigational. Radiation should be included as part of the standard treatment for sel ected patients with unresectable stage III NSCLC, whose performance st atus and pulmonary function are adequate. Definitive-dose thoracic rad iotherapy should be no less than 60 Gy in 1.8- to 2-Gy fractions. Loca l symptoms from primary or metastatic NSCLC can be relieved by judicio us use of radiotherapy. In appropriately selected patients, hypofracti onated palliative radiotherapy (of one to five fractions instead of 10 ) may provide symptomatic relief with acceptable toxicity in a more ti me-efficient and less costly manner. In patients with controlled disea se except for an isolated cerebral metastasis in a resectable area, re section followed by radiotherapy is superior to radiotherapy alone. Th ere is no role for the routine use of CAT scan of the chest or of othe r sites, bone scan, bronchoscopy, or routine blood studies in asymptom atic patients nor undergoing therapy. Prevention by smoking cessation and avoidance of occupational and environmental exposure to carcinogen ic substances are effective interventions to reduce the risk of second primary NSCLC. The use of antioxidants and/or chemopreventive agents for NSCLC is investigational. New evidence will be evaluated by annual update of these guidelines. (C) 1997 by American Society of Clinical Oncology.