Annals of Oncology 17 (Supplement 2): ii17–ii21, 2006 doi:10.1093/annonc/mdj913 symposium article Non-small cell lung cancer: early stages E. Bria 1 *, A. Ceribelli 1 , M. G. Trovo ` 2 , A. Gelibter 1 , M. Gigante 3 , E. Calabro ` 3 , F. Cuppone 1 , F. Cognetti 1 , E. Terzoli 1 & U. Pastorino 3 1 Department of Medical Oncology, Regina Elena National Cancer Institute, Roma; 2 Department of Radiation Oncology, C.R.O., National Cancer Institute, Aviano; 3 Thoracic Surgery, National Cancer Institute, Milan, Italy introduction More than 170 000 new cases and 150 000 deaths have occurred in 2003 in US owing to lung cancer, which is the leading cancer death reason for men in US. Non-small cell lung cancer (NSCLC) accounts for about 80% of all lung cancers [1, 2]. Despite the progress in imaging and diagnostic procedures, non-small cell lung cancer (NSCLC) usually presents as advanced (locally or more frequently disseminated), and a small part (around 30%) has to be considered early stage [1]. For early stage disease, surgery still remains the treatment choice, even if the majority of patients will undergo progression after complete tumor resection. In order to increase curable rate us such social disease, progresses in diagnosis technique and treatment approaches have been recently developed. diagnosis and screening Non small cell lung cancer cure rate is significantly increased when the patient undergoes surgery; this scenario strongly stresses the crucial role of early diagnosis and screening too [3]. Recent advances in imaging techniques, such as spiral computed tomography (CT) improved the early diagnosis rate while new issues have been opened owing to charming and promising results coming from screening trials [4] In this direction, the treatment strategy to apply in patients with lung cancer discovered into a screening plan, needs to be explored in a randomized fashion. In 2000, the National Cancer Institute in Milan launched a pilot trial to investigate the efficacy of yearly spiral CT and positron emission tomography (PET), combined with blood and sputum biomarkers, in a large cohort of high-risk volunteers [5]. This study enrolled 1035 heavy smokers (20 pack/years) aged 50+ to undergo annual low-dose CT±PET for 5 years. Lesions up to 5 mm were deemed non-suspicious and sent to repeat low-dose CT after 12 months, while PET was applied to lesions greater than 7 mm, after HRCT. At the end of 5th year, the final compliance rate was 85%, the cumulative recall rate for HRCT 17% and PET rate only 1.4% (69/4818 low-dose CTs). A total of 38 primary lung cancers were diagnosed, with complete resection in 33 (87%) and 24 (63%) pathological stage I. There were no pneumonectomies or perioperative deaths, and 63% of patients were alive and disease-free (96% of stage I). The innovative design of this pilot study, combining spiral CT and selective PET with a conservative approach to smaller lesions, proved to be safe and effective. Based on these results, a new multicentric prospective randomized trial was launched in Northern Italy. The new study, named Multicentric Italian Lung Detection trial (MILD), is expected to recruit 10 000 individuals (50+ heavy smokers), with a total intervention period of 10 years, randomized in 2 groups: a control group undergoes to a program of primary prevention with pulmonary function test evaluation and a group to periodic spiral CT associated with primary prevention and pulmonary function test evaluation. The last one is randomized in two arms: yearly low-dose CT vs. CT every 2 years. Primary end-point of the study is the assessment of smoking cessation percentage and ultimate impact of early lung cancer detection on mortality. Last generation CT (16sl) and CT/PET is combined with genomic and proteomic analysis on plasma samples. adjuvant chemotherapy In order to improve survival of patients affected by early stage NSCLC, randomized phase III trials have been conducted to look if complementary radiotherapy and/or chemotherapy add any benefit over exclusive surgery. A meta-analysis of more than 2000 patients showed that radiotherapy doesn’t add any benefit over surgery alone in overall survival, while a recurrence reduction is provided, and should not be considered as standard treatment [6]. Extra-thoracic relapse can explain this effect and suggests the adjunction of adjuvant chemotherapy. To date, although for advanced disease the benefit of chemotherapy over best supportive care is worldwide well- defined [7, 8], and for locally advanced is promising when combined with radiotherapy, its role in adjuvant setting is still controversial. Furthermore, the historical meta-analysis conducted by the NSCLC Collaborative Group showed that chemotherapy yielded a not significant benefit in survival over surgery alone [7], although a positive trend was seen. Nine randomized clinical trials (RCTs) have been recently completed and published with conflicting results. Two symposium article *Correspondence to: Dr. Emilio Bria, Department of Medical Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Roma, Italy. Tel: +390652666222; Fax: +390652666219; E-mail: emiliobria@yahoo.it ª 2006 European Society for Medical Oncology by guest on April 26, 2016 http://annonc.oxfordjournals.org/ Downloaded from