VIEWS: 11 PAGES: 9 CATEGORY: Medicine POSTED ON: 7/14/2010
CONTEXT: Recent advances in human imaging technologies reawakened interest in lung cancer screening. Although historic and current preliminary and noncontrolled studies have not shown a decrease in lung cancer mortality in screened populations, many explanations have been proffered while the lung cancer community awaits the results of several large controlled population studies. OBJECTIVE: To critically review the current model of adenocarcinoma development against the background of lung cancer screening results combined with observational pathologic and radiographic studies. DATA SOURCES: Published articles pertaining to lung cancer screening, lung adenocarcinoma pathology, and radiology accessible through PubMed form the basis for this review. CONCLUSIONS: The current adenocarcinogenesis model is probably valid for many but not all lung adenocarcinomas. Screening data combined with radiographic and pathologic studies suggest that not all lung adenocarcinomas are clinically aggressive, and it is uncertain whether all aggressive adenocarcinomas arise from identified precursors.
High-Resolution Computed Tomography Screening for Lung Cancer Unexpected Findings and New Controversies Regarding Adenocarcinogenesis Lucian R. Chirieac, MD; Douglas B. Flieder, MD ● Context.—Recent advances in human imaging technol- Data Sources.—Published articles pertaining to lung ogies reawakened interest in lung cancer screening. Al- cancer screening, lung adenocarcinoma pathology, and ra- though historic and current preliminary and noncontrolled diology accessible through PubMed form the basis for this studies have not shown a decrease in lung cancer mortality review. in screened populations, many explanations have been Conclusions.—The current adenocarcinogenesis model is probably valid for many but not all lung adenocarcino- proffered while the lung cancer community awaits the re- mas. Screening data combined with radiographic and path- sults of several large controlled population studies. ologic studies suggest that not all lung adenocarcinomas Objective.—To critically review the current model of ad- are clinically aggressive, and it is uncertain whether all enocarcinoma development against the background of lung aggressive adenocarcinomas arise from identiﬁed precur- cancer screening results combined with observational sors. pathologic and radiographic studies. (Arch Pathol Lab Med. 2010;134:41–48) G iven the aggressive nature of lung cancer and the gen- eral inability of the world to curtail the abuse of tobacco products, we now must confront the bitter truth dividuals continues—and its future as a public health pol- icy is unknown—the dialectic has produced an original and thoughtful reexamination of our most basic accepted that lung cancer is the deadliest human cancer worldwide notions regarding lung adenocarcinoma. This review aims and that current treatment options are just not adequate. to present our evolving understanding or lack of under- Recent medical advances in lung cancer care include standing of lung adenocarcinoma within the context of noninvasive and minimally invasive methods of diagnos- lung cancer screening. ing and treating lung cancer and pharmacogenetic ap- proaches to chemotherapy selection. However, technologic ADENOCARCINOMA OF THE LUNG AND advances have truly reinvigorated lung cancer clinicians LUNG CANCER SCREENING FINDINGS and researchers alike. Although chest x-ray screening for Not unlike cancer models employed in other organ sys- lung cancer was left for dead following the disappointing tems, the current lung adenocarcinoma model assumes a results of the Mayo Clinic (Rochester, Minnesota), Johns progression from a few malignant cells to a group of cells Hopkins (Baltimore, Maryland), and Memorial Sloan-Ket- to a small ‘‘early-stage’’ carcinoma, leading to ‘‘advanced- tering (New York, New York) studies from the 1970s, high- stage’’ carcinoma and death. This model suggests that all resolution computed tomography (HRCT) screening has lung adenocarcinomas are stage I before progressing to forced lung cancer specialists to reconsider their long-held higher stages and causing death.1,2 Thus, early-stage and assumptions about the disease. The past 10 years have wit- nessed an accelerated pace in the radiologic characteriza- late-stage carcinomas are separated only by time and the tion of lung lesions and the histologic classiﬁcation of lung molecular events that occur during this time. This long- adenocarcinoma. accepted scheme appears reasonable and provides the Although the ﬁerce and often acrimonious debate re- framework for much research; however, lung cancer garding the efﬁcacy of HRCT screening of high-risk in- screening data do not convincingly support this general view.3 Lung cancer screening with early detection should lead to an increase in early-stage cancers, a decrease in Accepted for publication February 12, 2009. late-stage cancers, and lower lung cancer mortality. Yet, From the Department of Pathology, Brigham and Women’s Hospital published data do not show these results and suggest that and Harvard Medical School, Boston, Massachusetts (Dr Chirieac); and perhaps not all clinically early lung adenocarcinomas pro- the Department of Pathology, Fox Chase Cancer Center, Philadelphia, gress to advanced lung cancers. Pennsylvania (Dr Flieder). Randomized trials of chest radiography with or without The authors have no relevant ﬁnancial interest in the products or sputum cytology performed in the 1970s noted a large companies described in this article. Reprints: Douglas B. Flieder, MD, Department of Pathology, Fox increase in early-stage cancers in the screened populations Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111 but not a meaningful decrease in the number of advanced (e-mail: Douglas.Flieder@fccc.edu). cancers.4–8 The Mayo Lung Project, London and Czecho- Arch Pathol Lab Med—Vol 134, January 2010 HRCT Screening for Lung Cancer—Chirieac & Flieder 41 slovakian studies, demonstrated a near doubling of the tically altered our
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