Imaging for the Pretreatment Staging of Small cell Lung Cancer

Background

Small cell lung cancer (SCLC) is an aggressive form of lung cancer. Accurate staging is essential to select the optimal treatment plan to maximize survival. No consensus exists on standard imaging modalities for pretreatment staging of SCLC.

Materials and Methods

We conducted a systematic review of the literature on imaging modalities in the pretreatment staging of SCLC. A systematic search of multiple databases identified relevant studies published from 2000 through June 2015. Outcomes of interest included test concordance, staging accuracy (sensitivity and specificity), choice of treatment, timeliness of treatment, and patient outcomes.

Results

The search identified 2880 citations; 7 studies met inclusion criteria, n = 408 patients. Six of the seven studies were deemed to have moderate risk of bias, and one was deemed to have high risk of bias. One of the studies reported test concordance, three studies reported comparative accuracy of testing strategies, and four studies reported the accuracy of a single imaging modality. Analysis from these studies revealed that fluorodeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) is more sensitive than multidetector CT for detecting osseous metastases, more sensitive than bone scintigraphy for detecting osseous metastases, and more sensitive for detecting any distant metastases.

Conclusions

Evidence is sparse on the use of imaging in the pretreatment staging of SCLC. There is a lack of evidence on patient-oriented outcomes and a lack of evidence on whether comparative accuracy or effectiveness is associated with patient factors. We found low-strength evidence suggesting that FDG-PET/CT is more sensitive than CT and bone scintigraphy for detecting osseous metastases.

Introduction

Lung cancer is the leading cause of cancer-related mortality, accounting for about 27% of cancer deaths in the United States in 2014 (1). Small cell lung cancer (SCLC) is an aggressive form of lung cancer characterized by rapid doubling time, high-growth fraction, and early development of metastatic disease. This histological subset of lung cancer is primarily seen in smokers (2) and accounts for approximately 15% of all lung cancers (1). Despite advances in diagnosis, treatment, and management of lung cancer, the 5-year survival rate for SCLC remains dismal at about 6% (1).

Staging involves determining the extent of disease and deciding on the treatment choice. SCLC is often staged using the Veterans Administration Lung Study Group system 3, 4, 5, which classifies SCLC as either limited stage disease (LD), wherein cancer is confined to one hemithorax, all of which can be encompassed in a safe radiotherapy field, or extensive stage disease (ED), which does not meet the criteria for LD. At diagnosis, the vast majority of patients with SCLC have ED, with overall long-term survival of only 1% 6, 7. Chemotherapy remains the standard of care for this stage of disease and is associated with improved overall survival and quality of life. LD is treated more aggressively, with a curative intent, with chemoradiation (7).

Because of SCLC's rapid progression, timely diagnosis and accurate staging are important (8). Performing potentially unnecessary tests during the diagnostic and staging process could delay treatment initiation, compromising treatment efficacy.

Various imaging modalities are currently in use for the pretreatment workup of patients with SCLC, including multidetector computed tomography (MDCT), positron emission tomography (PET) 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, magnetic resonance imaging (MRI) (21), and bone scintigraphy (21). Although not an imaging modality, endobronchial ultrasonography (EBUS) (22) is often used for initial diagnosis with the help of EBUS-guided transbronchial needle aspiration (22) and for mediastinal staging.

The performance of various imaging modalities may be affected by comorbidities such as renal insufficiency, which potentially limits the use of intravenous contrast material for MDCT or MRI. Generally, body habitus may limit the diagnostic quality and accuracy for any imaging modality. Many scanners are unable to safely accommodate patients above a particular weight. Tumor characteristics may also be associated with comparative accuracy and effectiveness.

A 2013 guideline from the American College of Chest Physicians (ACCP) recommended that patients with either proven or suspected SCLC undergo CT of the chest and abdomen or CT of the chest extending through the liver and adrenal glands, as well as MRI of the brain and bone scintigraphy (7). In 2014, the American College of Radiology (ACR) appropriateness criteria review gave the highest rating of “usually appropriate” (for staging SCLC) to the following specific modalities: CT of the chest and abdomen with contrast, MRI of the head with and without contrast, and FDG-PET/CT from skull base to mid-thigh. ACR rated bone scintigraphy as “may be appropriate” and considered unnecessary if PET/CT had been performed (21).

Our aim for this review was to synthesize the literature on whether some imaging modalities are better than others for the pretreatment staging of SCLC. We searched for evidence on comparative accuracy (sensitivity, specificity) as well as subsequent clinical outcomes (choice of treatment, survival, and quality of life).