10 MDCT Screening for Lung Cancer:
Current Controversies
F. L. Jacobson
F. L. Jacobson, MD, MPH
Department of Radiology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA
CONTENTS
10.1 Lung Cancer: The Opportunity for Screening 145 10.2 Prevention of Lung Cancer 145
10.3 Criticisms of Lung Cancer Screening 146 10.4 MDCT and Lung Cancer Screening 147 10.5 Low-Dose CT Screening Program 147 10.6 CT Scanning Parameters 147 10.7 MDCT Imaging Findings 148 10.8 Interpretation of Screening CT 150 10.9 Algorithms for Follow-up 151 10.10 Patient Expectations 151 10.11 Current Status 151 10.12 Current Controversies 152 10.13 Conclusion 153
References 153
10.1 Lung Cancer:
The Opportunity for Screening
Lung cancer is currently the most common cause of cancer death in men and women in the United States (Travis et al. 1996). Approximately 171,900 new cases of lung cancer will be diagnosed in the United States in 2003 and 157,200 individuals are expected to die of the disease (American Cancer Society 2003).Despite the development of effective multimodality treatments, mortality from primary lung cancer has continued to rise over the past three decades; approximately 85%
of those who develop lung cancer die from it (Fry et al. 1996). More Americans die from lung cancer than colon, breast, and prostate cancers combined.
Small-cell lung cancer accounts for approximately 25% of lung cancers. Small-cell lung cancer is usually a systemic disease at initial presentation due to its aggressive nature with early dissemination through- out the body. Outcome is not improved by screening.
Non-small cell lung cancer (NSCLC) accounts for approximately 75% of all lung cancers. The progno- sis in patients with NSCLC follows surgical stage at the time of diagnosis. Overall 5-year survival from lung cancer remains less than 15% (Fry et al. 1996);
however, patients with surgically resected early stage NSCLC have 5-year survival rates of up to 70% or more (Martini et al. 1995). Five-year survival in a cohort of 598 patients with surgically resected stage I tumors was recently reported as 75%; however, when stratifi ed by TNM tumor classifi cation, patients with T1 tumors fared better than those with T2 tumors, with 5-year survival rates of 82% and 68%, respectively (Martini et al. 1995; Flehinger et al. 1992).Small tumor size at time of diagnosis and treatment is associated with longer survival, particularly when tumors are less than 1 cm in diameter. This improvement in survival forms the primary rationale for the early detection of lung cancer using multi-detector CT (MDCT) screening.
10.2 Prevention of Lung Cancer
Cigarette smoking is associated with 85% of lung cancers and is the single most important risk factor for lung cancer (Doll and Peto 1981; US Depart- ment Of Health, Education And Welfare 1979;
Burns 1994; Strauss et al. 1995; Reizenstein et al. 1994). Although the prevalence of smoking has decreased in the 30 years since the fi rst report by the United States Surgeon General on the causal relationship between smoking and lung cancer in men, the annual cancer statistics of the American Cancer Society have only recently begun to show any decrease in lung cancer incidence in men and, in fact, continue to demonstrate increasing incidence of lung cancer in women. Women are entering a period of increased risk based on the 20 to 30 year latency period measured from the introduction of fi ltered cigarettes marketed specifi cally to women (Ameri- can Cancer Society 2003).
More than 50% of lung cancers are now diagnosed in former smokers. For this population, primary prevention, in the form of smoking cessation, is not adequate to prevent deaths due to lung cancer.
The selection of criteria for screening is based upon the relative risk of lung cancer as infl uenced by duration of smoking, intensity of exposure, and duration of smoking cessation in ex-smokers. Risk increases in rough proportion to the number of cigarettes smoked per day (Hammond 1966; Rogot and Murray 1980). Duration-specifi c risks increase steadily, but are most signifi cant beyond 20 years of smoking duration. Cancer risk remains elevated in former cigarette smokers, declining signifi cantly beyond 5 years from cessation. Lung cancer occurs primarily in patients between ages 50 and 80 years.
The relative risk of lung cancer is also infl uenced by family history, occupational exposures, and the pres- ence of airfl ow obstruction (Tockman et al. 1987;
Nomura et al. 1991). Lung cancer prevalence is high among individuals with minimum 30–40 pack year histories of smoking and airfl ow obstruction, defi ned by FEV1/FVC less than 70% of predicted value and FEV1 less than 70% of predicted value (Kennedy et al. 1996).Airfl ow obstruction is associated with a 4–5-fold increase in lung cancer (Tockman et al.
1987; Nomura et al. 1991). Cancer risk is presumably increased by poor clearance of carcinogens. The cor- relation between small size of tumor and localized disease may not be as simple as selecting early stage disease however (Patz et al. 2000).
Individuals with previously resected stage I NSCLC are at the highest risk for the development of primary bronchogenic carcinoma (Flehinger et al. 1992; Jones et al. 1995; Marcus et al. 2000). The second lung cancer may be of the same or a different histology; the latter case increasing confi dence that the tumor is indeed due to a metachronous primary and not a metastasis of the original primary.
10.3 Criticisms of Lung Cancer Screening
Lung cancer screening is criticized in different ways by ethicists, epidemiologists, and cancer biologists.
The ethical question of whether it should be per- formed outside of a clinical trial is subject to change.
The position of epidemiologists can be presented with the history of screening studies. The biases with which they are concerned are of importance also to individual patients and do warrant attention as pre-
sented in the following paragraphs. Tumor biology is incompletely understood and far more complex than previously thought. The possibility of preclinical dis- ease in an asymptomatic individual already having metastasized challenges the basic assumptions made when screening. It may not be easy or straightforward to determine who will benefi t from MDCT screening for lung cancer, at least until we have complementary biomarker screening tests.
Lung cancer screening with chest radiographs has been studied fairly extensively, beginning with stud- ies in the 1950 s and including mass screening stud- ies in the 1970 s. The Mayo Lung Project (MLP) has now followed every participant to a mortality specifi c outcome (Marcus et al. 2000; Marcus and Prorok 1999). Forty-six excess, largely early stage, lung cancers occurred in the screened group. Late stage cancers were not decreased and nor was lung cancer-specifi c mortality. The excess lung cancers in the screened participants have been explained by: over-diagnosis of lung cancer in the screened group and under-diag- nosis of lung cancer in the control group. This mis- classifi cation of the cause of death is diffi cult to avoid in such a trial when the experimental group receives greater scrutiny than the control group. The conten- tion that the risk profi les of the two groups were not equivalent is not supported by the recent re-analysis of the risk-defi ning features of the two groups (Marcus et al. 2000; Marcus and Prorok 1999).
Despite the historical lung cancer screening trials and the reevaluation of the Mayo Clinic MLP data after the death of all of the subjects in that trial, there is cur- rently no recommendation by any national organiza- tion for lung cancer screening (Marcus et al. 2000).
The National Cancer Institute has initiated a large ran- domized population trial using MDCT and PA chest radiographs for lung cancer screening to determine whether screening can reduce lung cancer-specifi c mortality by at least 20%. The National Lung Screen- ing Trial (NLST) has begun enrolling 50,000 subjects through the American College of Radiology Imaging Network (ACRIN) and the Prostate-Lung-Colon- Ovarian (PLCO) Intramural study groups.
Randomized population trials overcome the biases of lead-time, length-time and over-diagnosis by allo- cating known and unknown factors randomly to both of the groups. Lead-time bias refers to the lengthened survival without alteration in mortality when disease is detected earlier but death is not delayed. Length bias pertains to the tendency of screening to detect slow growing cancers as slow growing cancers have a longer preclinical phase. Such tumors may have more indolent biology and growth potential com-
pared with fast growing tumors that are less likely to be detected by screening. Over-diagnosis bias refers to the detection of a lung cancer that would have remained undetected during the patient’s lifetime, prior to death from other causes. When diagnosed, such tumors are referred to as “pseudo-disease.”
Small studies indicate that individuals with clinical stage I lung cancer who have not been treated by sur- gical resection, experience 80% mortality at 10 years.
However, high mortality does not imply that all lung cancers are lethal, only that clinically known lesions are lethal (Sobue et al. 1992). Published reports have documented unexpected “surprise” lung cancers at autopsy in individuals who have died from condi- tions such as coronary artery disease. Also, it is well known that small lung lesions less than 2 cm in diameter may be easily overlooked at autopsy due to sampling error. The reported necropsy “surprise”
detection rates suggest that there may be a signifi cant reservoir of asymptomatic lung cancer.
10.4 MDCT and Lung Cancer Screening
MDCT is the catalyst in low dose CT screening for lung cancer. Spiral (helical) CT allowed imaging of the thorax with a single breath using 8–10 mm thick images obtained in a single breath-hold. With repeated hyperventilation, patients with signifi cant pulmonary pathology are able to hold their breath for 30 seconds.
Spiral CT demonstrates smaller and smaller nodules with each incremental improvement in technology.
The threshold of visibility for nodules has decreased to 2–3 mm. Optimum imaging of nodules this small requires scan thickness in the 1–2 mm range, thus the thin section images so readily available with MDCT are a fundamental requirement for lung cancer screening. Overlapping reconstruction of images and review on a workstation, rather than fi lm, are also fi rst principles in the performance of lung cancer screening with MDCT. A bit of math will reveal the order of magnitude increase in the number of images generated by an individual MDCT examination. As this is counterintuitive for a screening examination, the management and effi cient manipulation of large image data sets is the current focus of industrial inter- est, research and development. The near isotropic pixel resolution of even four-row systems allows thin sec- tion overlapping reconstructions necessary for image processing and computer aided detection. Computer- aided detection and more broad applications foster-
ing computer-aided diagnosis will hopefully ease the burdens imposed upon the radiologist in performance of MDCT for lung cancer screening in the future. Even now, we see promise in the use of alternative display strategies such as Maximum Intensity Projections (MIP) with thicker slab presentations from which very small nodules are readily identifi ed.
10.5 Low-Dose CT Screening Program
A successful lung cancer screening program can be modeled from a successful breast cancer screening program. The service is provided to asymptomatic individuals who are at risk of developing a specifi c disease. Just as mammography is performed with risk assessment so should lung cancer screening. The patient also appreciates being given an indication of the preliminary result, when possible, at the conclu- sion of the examination. The involvement of primary care physicians may vary depending on whether referral is required. In any center that accepts self- referral, follow-up responsibilities will remain with the radiology practice. Of course, scanning, any supportive image processing and image interpreta- tion remain at the core of the radiology practice.
Financial arrangements for the examination may be handled differently than for diagnostic radiology services as insurance reimbursement is limited to interested HMOs. Advanced Benefi ciary Notices may be required depending on the institution. A separate brochure that presents an overview of the lung cancer screening, process, risks, and benefi ts can be helpful to patients deciding if they want to have this test. It is important for the physician and patient as well as the radiologist to understand that current knowledge is limited (Berlin 2002). The consensus statement of the Society of Thoracic Radiology provided con- servative criteria by which clinical screening services may be undertaken outside of clinical trials, in the absence of a mandate for mass lung cancer screening (Aberle et al. 2001).
10.6 CT Scanning Parameters
MDCT scanning for lung cancer screening requires consideration of technical scanning parameters (Table 10.1). With hyperventilation, patients hold
their breath in maximal inspiration for 20–30 sec- onds without diffi culty. Dose may be reduced sig- nifi cantly when imaging the lungs, with 120–140 kV and 20–80 mAs resulting in satisfactory studies. Col- limation of 1 mm with fi eld of view limited to the lungs will produce high quality images. Reconstruc- tion kernel should be chosen to minimize artifact- simulating calcifi cation as well as provide the edge enhancement preferred for lung images. Thin sec- tion images should be reconstructed with 20–50%
overlap. It is helpful to also keep standard thickness images for future comparison with diagnostic CT scans, as the best comparison is between images of the same scan thickness.
10.7 MDCT Imaging Findings
Many of the fi ndings seen on low dose MDCT refl ect the disease processes seen in individuals who smoke without alteration due to the reduction in dose. Sec- tion thickness affects appearance of images in the same manner as on full dose MDCT. The areas in which the dose reduction is noticeable are the medi- astinum and soft tissues, particularly of the upper abdomen.
Apical scarring frequently has both pleural and parenchymal components. The parenchymal compo- nents frequently include nodular opacities, particularly inferiorly, although these may often be understood in 3D as the inferior aspect of a linear feature. Thin sec- tion examination frequently reveals calcifi cation in an associated granuloma not appreciated on thicker sec- tions. The benign nature of a scar is best confi rmed by documenting stability over time. Conversely, changes in scars can be the primary sign of the development of lung cancer. This can take the form of a convex mass or
thickening of a linear structure in an area of emphy- sema. An additional area in which linear scars or bands or atelectasis are frequently found is the lung bases, particularly in the regions of the costophrenic sulci.
Emphysema and chronic infl ammatory changes are also frequent fi ndings. When studies are per- formed only when patients are in “their best usual state of health,” acute infl ammatory changes are less frequently encountered. Bronchiectasis and bronchial wall thickening without dilatation are often seen and can be complicated by mucous simulating a nodule.
Centrilobular opacities usually have a characteristic appearance with ill-defi ned margins (Fig. 10.1). The nodule will measure less than 4 mm in diameter and may be of soft tissue or, more commonly, ground- glass density. This type of opacity may be visible only on thin section images.
Intrapulmonary lymph nodes are frequently found as non-calcifi ed ovoid soft tissue nodules in subpleural regions. A very characteristic location is along the posterolateral aspect of the lower lobes.
Diagnosis is more diffi cult when the location is less typical or the nodule grows (Fig. 10.2). Remember too that the ovoid characteristic may be expressed in the z-axis direction.
Smoothly marginated nodules are benign by radiographic criterion only when they exhibit the solid or central calcifi cation characteristic of calci- fi ed granulomas (Fig. 10.3). Such nodules do not require further CT follow-up, whether this is deter- mined on an initial or subsequent CT scan, or even if well seen measuring less than 5 mm in diameter on a high kV radiograph. Thinner sections are defi nitely more helpful in this regard as well.
Table 10.1. MDCT Technical Parameters
MDCT parameter Lung cancer screening Detector collimation <or=to 1 mm Gantry rotation time 0.5–0.8 second Table speed (mm/rotation) 12–25 mm
Pitch 1.5 kV 120–140
Effective mA 20–80
Nominal slice width 1.25–2 mm Reconstruction interval <or=to 1 mm Reconstruction algorithm Standard/lung CTDI vol (dose in mGy) 3–4 mGy
Scan time 7–20 seconds
Fig. 10.1. 2 mm CT image demonstrating characteristic small centrilobular ground-glass opacity (GGO) with ill-defi ned margins. Opacity was not visible on 5 mm image
Fig. 10.2. a, 8 mm CT image 2 years prior to screening b, 5 mm image 1 year prior to screening and c is 2 mm CT image from low-dose CT screening. The nodule was resected due to question of growth raised largely due to comparison between images of different scan thick- ness. Nodule proved to be an intrapul- monary lymph node. A lymph node can grow without indicating malignancy
a
c
b
Non-calcifi ed soft tissue nodules are indetermi- nate and can be benign or malignant regardless of margins, although spiculated borders suggesting desmoplasia are clearly more worrisome for tumor.
Evaluation is dependent upon size, appearance of the lesion and the surrounding lung as well as the loca- tion and its accessibility for biopsy.
Ground-glass opacity, on MDCT for lung cancer screening, can be diffi cult to judge when no vessel may be immediately adjacent to the opacity that should not be obscured by it. This is frequently the result of partial volume effect upon a tiny soft tissue, or “solid”
nodule. Transient infl ammatory opacities can have this appearance as can opacities below the level of res- olution by the imaging system, as seen with interstitial lung disease and honeycombing. This designation is also used for opacities that may have structure without mass, making them more worrisome for bronchoal- veolar cell carcinoma (Fig. 10.4). Patients may have multiple lesions, with both adenocarcinomas and bronchoalveolar cell carcinomas. Recent reports in the literature indicate potential for tumor and persistent presence without progression or other evidence of signifi cant abnormality (Kodama et al. 2002).
Fig. 10.3. a and b lung and mediastinal windows of 5 mm images revealing a tiny subpleural nodule in right upper lobe with- out demonstration of calcifi cation. c and d lung and mediastinal windows of 2 mm images at the same table position dem- onstrating calcifi cation in the same tiny subpleural nodule, confi rming it is a calcifi ed granuloma.
When calcifi cation is identifi ed, no further
follow-up is required c
b
d a
The most controversial category of opacities cur- rently recognized in reporting MDCT for lung cancer screening is the part-solid mixed with ground glass opacity (Fig. 10.5). This may be symmetric or asym- metric. The association with cancer is high com- pared with solid only and ground-glass only nodules (Henschke et al. 2002). It too can be infl uenced by slice selection and scan thickness however.
10.8 Interpretation of Screening CT
Technological improvements leading to multi-detec- tor CT and the prevalence of small benign nodules in normal individuals suggest that the use of strict criteria for screening will result in increasing num- bers of patients having positive screening CT studies (Swensen 2002). The concept of choosing criteria by which to focus on a subset of study abnormalities is not a new concept. In the Early Lung Cancer Action Program (ELCAP), the large numbers of nodules, beginning with more the 6, were classifi ed differently, as they were more likely related to a process such as prior granulomatous infection than lung cancer.
The National Lung Screening Trial (NLST) does not catalog, nodules measuring less than 4 mm in diam-
eter that will not undergo interim follow-up imaging between annual screening CT examinations. At this time, these are decisions made for specifi c protocols.
Given the large number of small benign nodules that are found in the periphery of normal lungs, future incorporation of some as yet unspecifi ed minimum size for nodule follow-up in the standard of care would be helpful to radiologists providing lung cancer screening CT.
Measurement remains cumbersome. Automated measurement tools are not yet widely available and do not perform all of the required measurements under all conditions. Opacities that are not composed of solid nodules, whether due to spiculations or com- ponents of ground glass opacities may continue to challenge these tools. The radiologist may be more consistent than an automated measurement tool when measuring ground glass opacities. Adjacent structures ranging from vessels to the mediastinum and the chest wall continue to create ambiguity for measurement although automated measurement will usually more consistently select such a margin than the radiologist.
The overlap between benign and malignant lesions by appearance may be greater in clinical practice than in the early clinical trials such as ELCAP. Reports may seem dated before the next time the patient reports for screening. Many patients choose not to return for screening on a continuing basis, based on current information.
Fig. 10.5. 5 mm image reveals solid opacity and ground-glass opacity. This type of opacity may be associated with benign or malignant disease. This one resolved on a subsequent study Fig. 10.4. 2 mm image reveals a peripheral nodule with air
bronchograms. This proved to be an adenocarcinoma with areas of bronchoalveolar carcinoma
10.9 Algorithms for Follow-up
Follow-up algorithms have been a recent focus of con- troversy and should be expected to continue to change, even perhaps before the fi rst follow-up exam would be scheduled for a patient having a positive screening CT today. The most defi nitive benign fi nding in a very small pulmonary nodule will remain calcifi cation.
Demonstration of characteristic, solid or central, calcifi cation associated with a granuloma, does prove that a nodule is benign. This is true whether this is the fi rst or any subsequent CT. Thinner sections and differences in slice selection result in demonstra- tion of calcifi cation in different nodules on different examinations.
Solid, non-calcifi ed nodules remain indeterminate.
When suspicion for malignancy is low, follow-up to demonstrate 2 years of stability remains the current standard of care. Most conservatively, this results in follow-up CT in 3 months, 6 months, 12 months and 24 months. This is based upon the model used in diagnos- tic examinations. In the case of a patient reporting for screening as an asymptomatic person without known disease, rather than a patient with a known tumor who might have metastases, consideration for follow- up in 6 months, 12 months and 24 months may also be appropriate. The provision of the technological ability to accurately and reproducibly detect small amounts of growth in small nodules in the clinical environment may alter these strategies in the future.
The National Lung Screening Trial will not be doing interim follow-up, at less that 12 months, for most nodules measuring less than 4 mm. While arbitrary, it does eliminate many classes of known benign opacities, including centrilobular opacities, many granulomas, and many micronodules. Lung nodules in this size range that actually represent can- cers that have not yet exhibited malignant features, even if due to the limitations of the imaging system, would of necessity have to have a slow to moderate growth rate in order to benefi t from screening by being found based upon growth a year later. These characteristics would be necessary for the lesion to be one to benefi t from early detection as well.
While tumors can metastasize at any size, it is helpful to review tumor growth in terms of screening and the opportunity to identify preclinical disease.
Part-solid and ground-glass opacities represent more active biological entities that may represent infl ammation, or, as demonstrated in the ELCAP experience, early lung cancer. The signifi cance of can- cers detected by screening is less well understood than
more advanced stage lung cancers that present with clinical signs and symptoms.
For low dose CT to provide successful lung cancer screening, the appropriate individuals will need to be selected. Examinations will need to be performed at specifi cally chosen intervals with carefully designed follow-up protocols. We do not yet have the necessary data to optimize detection while minimizing morbidity and mortality associated with evaluation of false posi- tive nodules identifi ed at screening. Decrease in lung cancer specifi c mortality from early detection through screening could be completely offset by morbidity and mortality associated with workup of false positive nod- ules and “pseudo-disease” that would not have become apparent during the normal lifetime of the patient.
Spiculated lesions and those larger than one cen- timeter require standard clinical investigation. PET- FDG imaging scan, biopsy, and surgical resection have roles in such lesions. The burden of work-up for false positive nodules will vary with location, gener- ally between 25-and 50%. The health care cost and attendant morbidity and mortality require careful consideration and the most conservative management possible. Biomarker assays may contribute more to the decision process in the future.
10.10 Patient Expectations
It is critically important for the radiologist to com- municate with the patient regarding the imperfect state of our knowledge regarding the value of lung cancer screening. It is not a substitute for primary prevention of lung cancer through smoking cessa- tion. It is not known whether earlier identifi cation of lung cancer can reduce the chance of dying from lung cancer. The patient needs to understand the pos- sibility of further tests and even surgery being recom- mended, with attendant complications of morbidity and mortality, as a result of having the test, even if no benefi t is ultimately realized.
10.11 Current Status
Low-dose CT screening is being performed in both clinical and research settings. Targeted populations include heavy smokers and those with occupational exposures to substances such as asbestos.
In baseline and 2 follow-up annual low-dose CT screening examinations of 1520 individuals, the Mayo Clinic has identifi ed 2832 nodules in 1,049 indi- viduals (89%). Forty cases of lung cancer diagnosed included 20 at prevalence screen and 10 at each sub- sequent annual incidence screening CT examination.
Thirty-eight cases were diagnosed by CT alone and 2 were diagnosed by sputum cytology alone. Two inter- val cancers were not detected by the screening exami- nations. The stages included 22 stage IA, 3 stage IB, 5 Stage II, 5 Stage II, and 1 Stage IV. All cell types were represented. Individuals in this trial were at least 50 years of age with a minimum 20 pack-year smoking history (Swensen et al. 2003). The results of this study provide realistic data regarding the confounding fac- tors in populations with signifi cant benign nodule forming exposures such as encountered in areas of endemic granulomatous diseases. Despite the high rate of granulomatous disease in this population, this CT screening project has been successful epidemio- logically with a very low rate of interval cancers. The data regarding sputum cytology suggests we should continue to seek roles for inexpensive screening tests in conjunction with CT.
These data encourage our screening efforts while we wait for the results of the National Lung Screen- ing Trial, now midway through its baseline, prevalence screen of 50,000 individuals. From this randomized population trial, we expect to fi nally learn whether early detection of lung cancer decreases lung cancer specifi c mortality. This has remained the missing piece of information amid increasing enthusiasm for offering the potential opportunity to escape the very poor prognosis of lung cancer. It is intuitive to think that, as with other forms of cancer, early detection will allow effective treatments to provide long-term control and true cure. We have not yet proved we are not identifying cases of lung cancer that would not otherwise come to clinical attention and limited life, a signifi cant concern incidental lung cancer necropsy rates of 16%. Many of the early trial that have allowed us to reach our current level of enthusiasm are subject to lead-time bias by reporting survival as a surrogate for mortality benefi t. Tumor biology is complex and we have barely scratched the surface in understand- ing the interaction between individual nodules. In any case screening will select for relatively indolent disease as the most aggressive tumors should be expected to present as interval cancers. Determining the true frequency of this event in large populations undergo- ing widespread screening for lung cancer will also be important for providing proper understanding of the limit of what screening can provide to the public.
Finally, our diagnostic methods will have to keep pace with our screening dilemmas. Non-invasive test- ing and more rapid ways of confi rming the benign nature of nodules on baseline screening examina- tions will also allow earlier identifi cation of the few nodules that represent early lung cancers. As we learn to sort nodules more specifi cally new screen- ing, diagnostic and therapeutic strategies will prob- ably emerge. Change is still needed to optimize our efforts using low-dose CT for lung cancer screening.
10.12 Current Controversies
Should we screen for lung cancer? After 50 years, this question has still not been answered. The studies looking at the ability of chest radiographs to decrease lung cancer mortality in the 1970 s, including the one done at The Mayo Clinic that has recently had follow- up mortality data obtained for all participants, failed to fi nd a decrease in mortality. In part, this represents limitations in study design, such as power, and fl aws that allowed the study and control groups to become more similar. Some limitations are simply unavoid- able such as the difference in detailed cause of death information for individuals in the two arms of the study. The depth of information is just not there regarding control subjects.
The urge to screen stems from the continued dismal prognosis of lung cancer, with 15% 5-year survival despite the improvements in treatment over the past 30 years. Lobectomy for Stage 1 A lung cancer pro- vides at least 70% 5-year survival. How to identify the patients who will benefi t from this surgery has been controversial because of the shift in tumor cell type to adenocarcinoma and its ability metastasize before reaching 7 mm in diameter. Surgery is not an adequate treatment for tumor that has already metastasized.
While no patient who has had a Stage 1 A lung cancer removed has ever been willing to have the tumor put back in his body, we have not yet proved that the inci- dentally discovered early tumors are the same tumors that would have gone on to kill the patients. It is for this purpose that we await the primary outcome data of the National Lung Screening Trial designed to determine whether screening with either PA chest radiograph or low-dose multidetector CT scan will decrease lung cancer mortality.
Once the mortality issue is better understood, the accumulating data will also point the next direction in creating an integrated screening program. CT
is expensive for use as a screening test. As such, it would be best if it could be used like colonoscopy, at milestone ages and relatively long intervals. Other tests, based on body fl uids, may well be used for more frequent monitoring and determining when to per- form repeat imaging. In this way, we may ultimately need to deviate from the annual imaging model of Mammography that has served us well in beginning to screen for lung cancer. Molecular imaging is an important horizon that should be incorporated into our screening and evaluation algorithms.
10.13 Conclusion
Lung cancer screening remains controversial because no decrease in lung cancer specifi c mortality has yet been demonstrated through early detection of dis- ease. The National Lung Screening Trial (NLST) has recently begun enrolling 50,000 smokers and former smokers, ages 55–74, in order to answer this impor- tant question. Lung cancer screening CT can be of benefi t to selected patients. Communication between radiologist, patient and physician is critical to suc- cessful low dose CT screening for lung cancer.
Until a standard of care is established, who should be screened, when, and by what modality will remain a subject of debate and variability. CT may ultimately be used in conjunction with an inexpensive screen- ing test performed on urine or blood. Criteria are needed that will maximize the identifi cation of asymptomatic lung cancers and decrease lung cancer deaths with the least burden on radiologists, patients and the health care system.
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