Screening for Lung Cancer

should people who smoke get regular chest  X-rays, CT scans or PET scans? Would this lower the mortality rates for lung cancer, which is the leading cause of cancer death?

7mm lung cancer, invisible on chest X-ray but seen only on CT scan
See the results of the new screening trials here , here, here and here and IELCAP site here

Currently, the ACS does not recommend testing for early lung cancer detection in asymptomatic individuals at risk for lung cancer. The ACS historically has maintained that patients at high risk of lung cancer because of significant exposure to tobacco smoke or occupational exposures and their physicians may decide to undergo testing for early lung cancer detection on an individual basis. Favorable findings from investigations using low-dose helical CT for testing for early lung cancer detection, have led to a large, prospective trial evaluating the relative efficacy of low-dose spiral CT versus chest radiography for the early detection of lung cancer in current and former smokers as well as direct promotion to the public of spiral CT for early lung cancer detection.

In its narrative, the ACS emphasized the importance of informed decision making for individuals who elect to be tested for early lung cancer detection and recommend that, ideally, testing should be done only in experienced centers that also are linked to multidisciplinary specialty groups for diagnosis and follow-up. Current smokers should be informed that the more immediate preventive health priority is the elimination of tobacco use altogether, because smoking cessation offers the surest route at this time to reducing the risk of premature mortality from lung cancer as well as cancers of other organs and a variety of nonneoplastic diseases.

In 2011 the National Lung Screen Trial (NLST) (go here) was published showing that low dose CT lung scans yearly for three years in high risk people (30 pack-year smoking history) will lower the risk of dying from lung cancer by 20%. And so in late 2011 the NCCN issued screening guidelines for high risk patients (go here)

 
What the Current Data Tell Us About Lung Cancer Screening
The data currently being reported from the single arm observational trials using chest x-ray or spiral CT underscore some of the challenges of both technologies. The first report was issued from the Early Lung Cancer Action Project (ELCAP) and compared the use of spiral CT and chest x-ray in a screened cohort of 1,000 individuals at risk of lung cancer. In this study, all subjects received both imaging tests. The authors reported that low-dose CT significantly outperformed conventional chest x-ray in the detection of small pulmonary nodules. Low-dose CT identified 233 participants with noncalcified nodules. Of these, there were 27 lung cancers; 23 cancers were Stage I at diagnosis. In contrast, conventional chest x-ray identified 68 noncalcified nodules, of which seven were malignant and four were Stage I. The diagnostic work-up of positive CT screens was based on initial nodule size or change in size on repeat imaging. Based on the average tumor size in the ELCAP study, the authors project a five-year survival of 80 percent for cases diagnosed using low-dose CT.

The Mayo Lung Trial has also published its results in an initial cohort of 1,520 participants who have undergone baseline and annual incidence screening with spiral CT. They have observed that 51 percent or more of baseline screens and up to 14 percent of annual incidence screens are positive for lung nodules, of which over 98 percent represent benign nodules. Among 40 lung cancers diagnosed thus far, 21 (60 percent) have been Stage I at diagnosis. Thus far, eight participants have undergone surgery for the resection of benign disease.

These studies highlight some of the issues surrounding evaluating a screening test. First, albeit more sensitive than chest x-ray, spiral CT is nonspecific. The high false positive rate imposes the potential for psychological, economic, and medical hardship on individuals who must undergo additional diagnostic tests based upon the finding of a nonspecific lung nodule on CT, and the challenge to identify best practices for minimizing adverse effects should not be neglected. Secondly, although lung cancers detected by CT are earlier stage than those detected with chest x-ray, it is not yet certain whether this apparent stage shift will result in a reduction in lung cancer mortality. We do not know, with measurable confidence, whether the detection of small lung cancers is tantamount to the detection of "early" curable cancers.

CT Screening for Lung Cancer: Past and Ongoing Studies.

Henschke CI,  Semin Thorac Cardiovasc Surg. 2005 Summer;17(2):99-106.

Department of Radiology, Weill Medical College of Cornell University, New York, New York.

The Early Lung Cancer Action Project (ELCAP), showed that false-positive results can be kept reasonably low and are much less common on repeat screening, and that CT screening can be managed with no notable excess of percutaneous or surgical biopsies when following a well-defined regimen of screening. This regimen details the parameters of the initial CT, the definition of a positive result, and the subsequent work-up of positive results. Following the updated International (I)-ELCAP protocol, it has been further found that (1) the frequency of positive results is low: 15% for the baseline cycle of screening and 6% for the subsequent cycles. (2) The frequency of screen-diagnoses as compared with all diagnoses is 97% or higher. (3) The relative frequency of presurgical Stage I is well over 80%; the median diameter of the screen-diagnosed cases on repeat screening is 8 mm (versus 15 mm at baseline screening). (4) A high percentage of the screen-diagnosed cases were genuine cancers which led to death if not treated. (5) The estimated 8-year cure rate for resected baseline screen-diagnosed lung cancers without evidence of lymph node metastases is 95% and for resected annual repeat cancers is 98%. (6) CT screening appears to be highly cost-effective. These preliminary results of CT screening suggests that the cure rate of screen-diagnosed lung cancer, using the I-ELCAP regimen of screening, may be over 70% as compared with that of usual care of 10% and that of chest radiographic screening of 20%.

Screening for Lung Cancer in High-Risk Groups: Current Status of Low-Dose Spiral CT Scanning and Sputum Markers.

Jett JR.  Semin Respir Crit Care Med. 2000;21(5):385-92.
Pulmonary Medicine and Medical Oncology, Mayo Clinic, Rochester, Minnesota.

Lung cancer is the number one cause of death from cancer in the United States. Currently, there is no official recommendation to screen for lung cancer even in high-risk populations. Accordingly, we wait for patients to present with symptoms. Only 15-20% of patients are stage I lung cancer at diagnosis. Past screening trials with chest roentgenogram and sputum cytology did not show a reduction of lung cancer mortality in the screened population. Since the completion of those trials in the early 1980s we have learned that the chest X ray is not sensitive at detecting lesions <2 cm in size, and patients with chronic obstructive pulmonary disease (COPD) have a 4- to 6-fold increased risk of lung cancer independent of their smoking history. Recent trials with spiral computed tomography (CT) scan screening have detected 80-85% of lung cancers while they are stage I. The problems related to spiral CT screening are the cost and the frequent detection of benign lesions. Algorithms are being developed to try and prevent unnecessary biopsies and/or surgery. Sputum cytology is currently the only clinically approved sputum test for detecting lung cancer. However, in patients with moderate dysplasia of cytology, the LIFE autofluorescence bronchoscopy system may yield an increased sensitivity of detecting precancerous or cancerous lesions. More studies are needed before the LIFE system can be adopted as a standard clinical tool. Currently, investigators are evaluating the sputum for early lung cancer detection markers. The marker that is the most developed is the monoclonal antibody to the heterogeneous nuclear ribonucleoprotein A2/B1 on the sputum epithelial cell surface. Encouraging preliminary results have been reported and trials are ongoing. The future looks bright for the field of lung cancer screening.


 Screening for Lung Cancer with Low-Dose Spiral Computed Tomography

STEPHEN J. SWENSEN, JAMES R. JETT,  Mayo Clinic, Rochester, Minnesota Am. J. Respir. Crit. Care Med., Volume 165, Number 4, February 2002, 508-513
 

we enrolled 1,520 individuals aged 50 yr or older who had smoked 20 pack-years or more in a prospective cohort study. One year after baseline scanning, 2,244 uncalcified lung nodules were identified in 1,000 participants (66%). Twenty-five cases of lung cancer were diagnosed (22 prevalence, 3 incidence). Computed tomography alone detected 23 cases; sputum cytology alone detected 2 cases. Cell types were: squamous cell, 6; adenocarcinoma or bronchioalveolar, 15; large cell, 1; small cell, 3. Twenty-two patients underwent curative surgical resection. Seven benign nodules were resected. The mean size of the non-small cell cancers detected by computed tomography was 17 mm (median, 13 mm). The postsurgical stage was IA, 13; IB, 1; IIA, 5; IIB, 1; IIIA, 2; limited, 3. Twelve (57%) of the 21 non-small cell cancers detected by computed tomography were stage IA at diagnosis. Computed tomography can detect early-stage lung cancers. The rate of benign nodule detection is high.

False-Positive Rates

After 2 yr of study, we have found 2,244 uncalcified lung nodules in 66% of our 1,520 screened participants. We estimate that approximately 98% of these are falsely positive findings. Assuming that our 13% incidence rate of indeterminate lung nodules continues, almost all patients will have at least one false-positive examination result after only a few years of screening. Henschke  found nodules in approximately 25% of screened participants, but they used computed tomography techniques (10-mm-thick sections and film [not workstation] viewing) that should allow detection of fewer small nodules. They also studied a population that may be expected to have a lower prevalence of fungal granulomas. However, none of the 2,244 lung nodules was calcified on 5-mm sections, and we do not have evidence from this study that a large proportion were granulomas. In fact, only two of the eight benign nodules removed were granulomas.