Benefits and harms of CT screening for lung cancer: a systematic review

Abstract

Context: Lung cancer is the leading cause of cancer death. Most patients are diagnosed with advanced disease, resulting in a very low 5-year survival. Screening may reduce the risk of death from lung cancer.

Objective: To conduct a systematic review of the evidence regarding the benefits and harms of lung cancer screening using low-dose computed tomography (LDCT). A multisociety collaborative initiative (involving the American Cancer Society, American College of Chest Physicians, American Society of Clinical Oncology, and National Comprehensive Cancer Network) was undertaken to create the foundation for development of an evidence-based clinical guideline.

Data sources: MEDLINE (Ovid: January 1996 to April 2012), EMBASE (Ovid: January 1996 to April 2012), and the Cochrane Library (April 2012).

Study selection: Of 591 citations identified and reviewed, 8 randomized trials and 13 cohort studies of LDCT screening met criteria for inclusion. Primary outcomes were lung cancer mortality and all-cause mortality, and secondary outcomes included nodule detection, invasive procedures, follow-up tests, and smoking cessation.

Data extraction: Critical appraisal using predefined criteria was conducted on individual studies and the overall body of evidence. Differences in data extracted by reviewers were adjudicated by consensus.

Results: Three randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality, of which the National Lung Screening Trial was the most informative, demonstrating that among 53,454 participants enrolled, screening resulted in significantly fewer lung cancer deaths (356 vs 443 deaths; lung cancer−specific mortality, 274 vs 309 events per 100,000 person-years for LDCT and control groups, respectively; relative risk, 0.80; 95% CI, 0.73-0.93; absolute risk reduction, 0.33%; P = .004). The other 2 smaller studies showed no such benefit. In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20% of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1% had lung cancer. There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions. Major complications in those with benign conditions were rare.

Conclusion: Low-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results.

Conflict of interest statement

Conflicts of Interest:

All authors have completed and submitted the ICJME form for Disclosure of Potential Conflicts of Interest. Dr. Azzoli, Dr. Brawley, Dr. Byers, Dr. Colditz, Mr. Mirkin, Mr. Oliver, Dr. Smith-Bindman and Dr. Qaseem have reported no conflicts. Dr. Bach reported that he has received speaking fees from Genentech. Dr. Detterbeck reported that he was reimbursed for travel costs associated with his work on the Oncimmune advisory board, and has participated without compensation in a symposium on CT screening sponsored by Covidien. Dr.Berry reported that he is co-owner of Berry Consultants LLC which designs adaptive clinical trials for pharmaceutical companies, medical device companies and NIH cooperative groups. To the best of his knowledge none of these parties have any interest in lung cancer screening. Dr. Gould reported that he receives grant support from the National Cancer Institute. Dr. Jett reported that he has grants pending for work related to screening and early detection of lung cancer with Oncimmune and Isense. Dr. Sabichi reported her membership on the National Cancer Institute’s PDQ Prevention and Screening Editorial Board and her possession of a pending patent for a test for the detection of bladder cancer. Dr. Wood reported his participation in the development of the National Comprehensive Cancer Network’s clinical practice guidelines for lung cancer screening in his role as Chair of the NCCN Lung Cancer Screening Panel.