Surveillance for the detection of early lung cancer in patients with bronchial dysplasia

Abstract

Background: The natural history of bronchial preinvasive lesions and the risk of developing lung cancer in patients with these lesions are not clear. Previous studies have treated severe dysplasia and carcinoma in situ (CIS) on the assumption that most will progress to invasive carcinoma. Aims: To define the natural history of preinvasive lesions and assess lung cancer risk in patients with these lesions. Hypothesis: Most preinvasive lesions will not progress to invasive carcinoma but patients with these lesions will be at high risk. Methods: A cohort of patients with preinvasive lesions underwent fluorescence bronchoscopy every 4-12 months and computed tomography of the chest annually. The main end point was the development of invasive carcinoma.Results: 22 patients with 53 lesions were followed up for 12-85 months. 11 cancers were diagnosed in 9 patients. Of the 36 high-grade lesions (severe dysplasia and CIS), 6 progressed to invasive cancers. 5 separate cancers developed at remote sites in patients with high-grade lesions. All cancers were N0M0 and curative treatment was given to 8 of the 9 patients. The cumulative risk of developing lung cancer in a patient with a high-grade lesion was 33% and 54% at 1 and 2 years, respectively. Of the 17 low-grade lesions, none progressed to invasive carcinoma. Conclusions: Although the risk of malignant progression of individual preinvasive lesions is relatively small, patients with high-grade lesions are at high risk of lung cancer. Surveillance facilitated early detection and treatment with curative intent in most patients.

SOX2 and PI3K Cooperate to Induce and Stabilize a Squamous-Committed Stem Cell Injury State during Lung Squamous Cell Carcinoma Pathogenesis

“…It is the earliest stage when common focal genetic changes are detected [36], and it is less prone to regression than earlier stages [28,33,34]. During this stage, we find that SOX2 and P-S6 are highly expressed in most cells.…”

“…The high expression levels could signify a largely stem cell-like population with strong commitment to the squamous fate. Because some high-grade dysplasias regress [29,32,33,105], the dysplastic phenotype is not likely to be strictly dependent on genetic alterations. We propose, however, that in order to regress, SOX2 and PI3K signaling levels must decline (Fig 13).…”

Indeterminate Pulmonary Nodules: Risk for Having or for Developing Lung Cancer?

“…If this assumption is correct, and if some NCNs represent precursor lesions, a successful therapeutic intervention would prevent these lesions from developing into cancer. In fact, the majority of lung nodules do not represent precursor lesions, few of the premalignant lesions progress (40, 45–47), and it is unclear whether chemoprevention strategies do prevent lung cancer development or allow regression of preinvasive lesions. Moreover, most of these lesions are not biopsied so it remains quite challenging to work with the lack of proven, histologic diagnosis for these lesions.…”

Natural history of bronchial preinvasive lesions

“…A significant proportion of the subjects were patients with previous lung or head and neck cancer. Some of the studies combined severe dysplasia with CIS [43] making it difficult to determine the natural history of these lesions separately. The study by Satoh et al illustrates the importance of long-term follow-up [44].…”