ONCAlert | 2018 ASCO Annual Meeting

Diagnosis, Staging, and Testing for Nonsquamous NSCLC

Published Online: Nov 20,2017
Non–small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 80% to 85% of lung cancer cases, whereas small cell lung cancer (SCLC) comprises approximately 10% to 15% of lung cancer cases.1 NSCLC originates from lung epithelial cells of the central bronchi to terminal alveoli,2 nonsquamous NSCLC will generally originate in peripheral lung tissue, and squamous cell carcinoma (SCC) primarily originates near a central bronchus.

Lung cancer, including both NSCLC and SCLC, contributes to the most cancer-related deaths in the United States, with 155,870 deaths estimated for 2017.2 Molecularly targeted therapies have been developed based on the identification of mutations in lung cancer, a move that has led to improved survival in specific subsets of patients with metastatic disease.3 Unfortunately, patients who do not harbor these mutations do not benefit from these new treatments and continue to experience poor outcomes. Being aware of current approaches to NSCLC diagnosis and assessment of disease criteria, relevant to current treatment selection strategies, is therefore a prerequisite for tailoring treatment for each patient.


Epidemiology and Risk Factors

NSCLC includes non–small cell carcinoma not otherwise specified (<5%), SCC (25%- 30%), and nonsquamous carcinoma (adenocarcinoma, large cell, and undifferentiated carcinoma; 70%-75%) (FIGURE 1).4,5 A recent systematic review reported that the median age at diagnosis of advanced NSCLC ranged between 59 and 68 years.6,7

An estimated 80% of patients with NSCLC receive an initial diagnosis after their cancer has already spread to regional lymph nodes or has metastasized, leading to 5-year survival rates of patients with stage IV cancer of <5%.4,5,7 A recent study’s results revealed that patients with nonsquamous NSCLC without known actionable mutations had a median overall survival (OS) of 10 months (95% CI, 9.4-10.8).8 Also, the results of a prospective cohort study of patients with metastatic NSCLC conducted in Australia revealed that patients with actionable mutations had a significant survival advantage compared with patients without actionable mutations (HR, 0.49; 95% CI, 0.33-0.71; P <.01).9
Smoking is the greatest risk factor for developing lung cancer, contributing to an approximate 10-fold increased risk compared with lifetime nonsmokers.2 The odds ratio estimate of developing lung cancer for patients who currently smoke versus patients who never smoked was 23.9 (95% CI, 19.7-29.0) in men and 8.7 (95% CI, 7.4-10.3) in women.10,11


Patients who have never smoked also develop NSCLC, with studies reporting frequencies up to approximately 30% (Japan).12,13 Although it has been suggested that lung cancer in never-smokers is a separate disease, descriptive studies are lacking, with many not including a comparison group of ever-smokers.14-16 A recent retrospective study reported that 22.4% of patients with newly diagnosed NSCLC were never-smokers and significantly more likely to be female (P <.001), older (P = .019), and have adenocarcinoma (P <.001).17

Other risk factors for lung cancer include secondhand smoke exposure; radiation exposure from radiation therapy to the chest or breast, radon exposure, medical imaging tests (ie, CT scans), or atomic bomb radiation; exposure to asbestos, nickel, chromium, arsenic, beryllium, soot, or tar in the workplace; chronic exposure to air pollution; a family history of lung cancer; HIV infection; and heavy smokers who take beta carotene supplements.2,18

Systemic anticancer therapy recommendations for patients with stage IV NSCLC depend on individual tumor histology, patient performance status, and driver oncogene biomarker status, which are most often anaplastic lymphoma kinase (ALK) translocations and epidermal growth factor receptor (EGFR) mutations (TABLE 1).18-21 Approximately 83% to 85% of patients with stage IV NSCLC do not have activating EGFR mutations or ALK translocations, requiring distinct first-line therapy recommendations.

Common sites of metastasis are other areas of the lung, the adrenal gland, and the brain.22 Of patients with advanced NSCLC, 25% to 44% experience dissemination in the central nervous system, particularly in patients diagnosed with adenocarcinoma.23, 24 Patients with brain metastases have particularly poor prognoses, leading to a median OS of 4 to 11 weeks or 4 to 15 months in untreated and treated patients, respectively.24,25

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Diagnosis, Staging, and Testing for Nonsquamous NSCLC
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