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The five-year survival for all stages of lung cancer combined is only about 15%, and the death rates in women have actually increased in the last decade as a result of changing trends in smoking habits between the sexes.
Cigarette smoking is by far the most important risk factor for the development of lung cancer, and the risk increases proportionately to both the duration and intensity of smoking exposure. Although smoking cessation is associated with a decrease in the risk for developing lung cancer, it never reaches baseline levels. Other risk factors include environmental exposure to carcinogens such as uranium, asbestos, silica, radiation.
Since all lung cancers are putatively derived from the bronchial epithelium lining the airways, they are also known as bronchogenic carcinomas. From a therapeutic point of view, lung cancers are conventionally divided into two broad histologic categories: small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). The reason for this dichotomy is that most SCLCs are widely metastatic by the time they are detected, and hence curative surgery is of little benefit; instead these patients are treated with systemic chemotherapy to which the neoplastic cells are fairly responsive, although the disease inevitably recurs. On the other hand, NSCLCs, when localized to the lung, have a possibility of surgical cure, with or without adjuvant therapy. The histologic subtypes that are included within the ambit of NSCLCs are squamous cell carcinomas, adenocarcinomas, and large cell carcinomas ("spindle and giant cell" carcinoma). For inexplicable reasons, adenocarcinomas have replaced squamous carcinomas as the most common histologic subtype of lung cancer. They are also the most frequent type of lung cancer seen in women, as well as in non-smokers.
Adenocarcinomas are gland-forming cancers, and are often more peripherally located than SCLCs or squamous cell cancers. The putative precursor lesion of adenocarcinoma is atypical adenomatous hyperplasia, characterized by a well-circumscribed focus of alveolar spaces lined by atypical "hob-nailed" epithelium. Atypical adenomatous hyperplasias share some of the genetic features associated with invasive adenocarcinomas, and are often present in the lung parenchyma adjacent to resected tumors. Bronchioloalveolar carcinoma is a special subtype of adenocarcinoma, which is characterized by growth along prexisting alveolar structures and absence of stromal invasion or parenchymal destruction. These have a better prognosis than invasive adenocarcinomas. Squamous cell carcinomas are distinguished by their ability to produce keratin and the absence of glandular differentiation. The development of invasive squamous cancers is often preceded for several decades by a variety of preneoplastic lesions in the bronchial epithelium such as squamous metaplasia, squamous dysplasia, and carcinoma in situ. There is progressive accumulation of genetic abnormalities in the histologic progression from metaplasia through carcinoma in situ to invasive cancer. Unlike squamous or adenocarcinomas, there is no identifiable precursor lesion for SCLCs, although it is postulated that they are derived from neoplastic transformation of the basally located pulmonary neuroendocrine cells within the bronchial epithelium.
Stage is a critical determinant of prognosis in lung cancers, and it drops from 48% for 5-year survival in localized disease to 18% in those with regional lymph node involvement. Histology is another determinant of prognosis. For example, adenocarcinomas have a better prognosis than small cell carcinomas. Several adjunct prognostic factors have been identified, including aneuploidy, telomerase dysregulation, activating mutations of ras oncogene, amplification of the c-myc oncogene, loss of Fhit and p16INK4a expression, and p53 inactivation, that are associated with adverse prognostic factors such as advanced stage and shortened survival. |
