James R. Jett, MD; David E. Midthun, MD
Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-1870.
Requests for Single Reprints: James R. Jett, MD, Department of Medicine, J307a, National Jewish Health, 1400 Jackson Street, Denver, CO 80206; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Jett: Department of Medicine, J307a, National Jewish Health, 1400 Jackson Street, Denver, CO 80206.
Dr. Midthun: Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905.
Author Contributions: Conception and design: J.R. Jett, D.E. Midthun.
Analysis and interpretation of the data: J.R. Jett, D.E. Midthun.
Drafting of the article: J.R. Jett, D.E. Midthun.
Critical revision of the article for important intellectual content: J.R. Jett, D.E. Midthun.
Final approval of the article: J.R. Jett, D.E. Midthun.
Provision of Study materials or patients: J.R. Jett.
Statistical expertise: J.R. Jett.
Obtaining of funding: J.R. Jett.
Administrative, technical, or logistic support: J.R. Jett, D.E. Midthun.
Collection and assembly of data: J.R. Jett, D.E. Midthun.
Jett J., Midthun D.; Screening for Lung Cancer: For Patients at Increased Risk for Lung Cancer, It Works. Ann Intern Med. 2011;155:540-542. doi: 10.7326/0003-4819-155-8-201110180-00367
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Published: Ann Intern Med. 2011;155(8):540-542.
Screening for lung cancer is not currently recommended, even in persons at high risk for this condition. Most patients with lung cancer present with symptomatic disease that is usually at an incurable, advanced stage. The recently reported NLST (National Lung Screening Trial) showed a 20% decrease in deaths from lung cancer in high-risk persons undergoing screening with low-dose computed tomography of the chest compared with chest radiography.
The high-risk group included in the trial comprised asymptomatic persons aged 55 to 74 years, with smoking history of at least 30 pack-years. Screening with low-dose computed tomography detected more cases of early-stage lung cancer and fewer cases of advanced-stage cancer, confirming that screening has shifted the stage of cancer at diagnosis and provides more persons with the opportunity for curative treatment. Although computed tomography screening has risks and limitations, the 20% decrease in deaths is the single most dramatic decrease ever reported for deaths from lung cancer, with the possible exception of smoking cessation. Physicians should offer computed tomography screening for lung cancer to patients who fit the high-risk profile defined in the NLST.
A 62-year-old woman with a history of well-controlled hypertension presents for routine follow-up. She is asymptomatic and feels well. She has jogged 3 miles 3 times weekly for years, with no recent change in exercise tolerance. She has a 30–pack-year history of cigarette smoking but stopped 10 years ago. There is no personal or family history of cancer.
Physical examination is normal. She read a recent study that found a benefit to screening for lung cancer with computed tomography and inquires whether you think screening is appropriate for her. What should you recommend?
Would we recommend that a 62-year-old woman with a 30–pack-year history of smoking undergo screening for lung cancer with low-dose computed tomography (LDCT)? Yes, but we would also discuss the potential risks and limitations as well as the potential benefits of screening before scheduling the test. If the patient currently smoked, we would strongly recommend a smoking cessation consultation and schedule it before or concurrent with LDCT (1). Smoking cessation significantly reduces the risk for lung cancer over time (2).
Most persons with lung cancer present with symptomatic disease at an advanced stage (stage III or IV) and at that point have little chance of curative treatment (3). Only 15% of patients with lung cancer in the United States are diagnosed with early-stage (stage I or II) disease, which is usually discovered incidentally on chest imaging studies done for other reasons (3, 4). Five-year survival with localized (early-stage) disease is 50% but only 4% in those with distant (stage IV) disease (3).
The NLST (National Lung Screening Trial) was a randomized, controlled trial of LDCT versus chest radiography screening in persons at high risk for lung cancer (5). High-risk persons were defined as being 55 to 74 years of age; having a smoking history of at least 30 pack-years; and, in former smokers, having quit smoking in the past 15 years. Participants received baseline and annual screening for 2 additional years and were followed for a median of 6.5 years. The patient framing our discussion meets the eligibility criteria for the NLST.
In the CT group of the NLST, 63% of cases of lung cancer diagnosed from a positive finding on a screening test were stage I and 70% were stage I or II (early stage). In 92.5% of cases, stage I lung cancer was treated with surgery (5). Treatment of stage I lung cancer offers the best chance of cure, with a 5-year survival rate of 70% to 80% (6). In the NLST, the LDCT group had fewer cases of stage IV cancer than did the chest radiography group at the second and third rounds of screening. These data show that, compared with chest radiography, screening with LDCT can shift the diagnosis of cancer from advanced- to early-stage disease and provide a better opportunity for curative treatment.
Screening with LDCT showed a 20% decrease in lung cancer deaths compared with chest radiography. To date, screening with chest radiography has not been shown to be superior to no screening. Patients who choose CT screening must understand that screening will diminish but not eliminate their chance of death due to lung cancer.
In the CT screening group, 356 deaths from lung cancer occurred (247 per 100 000 person-years) compared with 443 deaths (309 per 100 000 person-years) in the chest radiography group. This 20% decrease in lung cancer deaths is arguably the single greatest advance in decreasing lung cancer deaths ever reported, with the possible exception of smoking cessation (2).
The NLST also demonstrated an all-cause mortality reduction of 6.7%, although this predominantly resulted from reducing deaths from lung cancer. Lung cancer caused 60% of the 121 excess deaths in the chest radiography group (5).
Screening for lung cancer has been shown to be a “teachable moment” for smoking cessation. Quit rates of smokers participating in screening trials have exceeded the 4% background quit rate per year in smokers. The 1-year quit rate for smokers in CT screening trials varies from 12% to 20% (7–9). To date, studies have not shown an increased smoking rate in persons with negative screening results and indicate that participants are not using negative findings to rationalize continuing or resuming smoking.
The lay media and opponents of screening have emphasized the risk for cancer from medical imaging studies but have routinely failed to quantify real risk. The radiation dose associated with CT screening of the chest is generally less than 2 mSv, whereas the dose of standard non–contrast-enhanced chest CT is 7 mSv (10).
Investigations of the NLST have estimated that the risk for radiation exposure from LDCT screening in 55-year-old smokers is 1 to 3 deaths from lung cancer per 10 000 persons screened and 0.3 new cases of breast cancer per 10 000 women screened. The cumulative mortality reduction in the NLST was 30 cases of lung cancer per 10 000 persons screened. The benefit–risk ratio clearly demonstrates benefit (5, 11, 12). The American College of Radiology and the Radiological Society of North America have rated the additional lifetime risk for fatal cancer from LDCT as “very low” (1 per 10 000 to 1 per 100 000 persons) (www.radiologyinfo.org).
If results from the initial LDCT are negative, should this 63-year-old former smoker have additional yearly LDCT screening, and if so, for how long? The NLST participants underwent 3 yearly CTs. The 3 rounds of screening did not demonstrate a substantial decrease in the cases of lung cancer per year (270, 168, and 211, respectively). An additional 367 cases of lung cancer were detected in the CT group in the 5-year follow-up after the initial 3 years of screening. The cumulative rate of new cases of and deaths from lung cancer did not decrease during the 8 years of observation after participants were randomly assigned to the CT or chest radiography screening group (5). Therefore, the NLST data support yearly screening for at least 3 to 5 years; perhaps by that time, new information will be available to guide decisions on the length and frequency of screening.
We recommend LDCT screening for this high-risk patient on the basis of age and smoking history alone. In the future, we are likely to use a risk prediction algorithm to better assess individual likelihood of developing lung cancer.
Persons at higher risk are more likely to benefit from screening. Current risk prediction models are approximately 70% accurate (13–15). A risk model recently developed on the basis of the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) accounts for the age, education level, body mass index, family history of lung cancer in first-degree relatives, history of chronic obstructive pulmonary disease, recent history of chest radiography, smoking status (current or former), pack-years smoked, and smoking duration (16, 17).
Each component contributed to the accuracy of the model. The risk model had good accuracy with an area under the receiver-operating characteristic curve for predicting lung cancer of 0.805. When the model was used in an external validation sample, the area under the receiver-operating characteristic curve was 0.784 for predicting the 9-year risk for lung cancer. This model does not work well for predicting risk in never-smokers.
Refinement of future models may include the presence or absence of genetic susceptibility variants for lung cancer (18–22). Extensive investigation is under way for serum biomarkers associated with lung cancer that are also likely to improve risk models (23–26). Measured pulmonary function data compared with a history of chronic obstructive pulmonary disease also will further augment risk prediction models (27–29).
In summary, we recommend LDCT screening for this patient at high risk for lung cancer to decrease her risk for death from this condition. Medicare and insurance companies presently do not reimburse patients for LDCT screening, but this decision is likely to change on the basis of the NLST results. The positive trial results strongly advocate that physicians discuss CT screening with patients who fit the risk profile of those in the NLST.
Screening should be done when desired by an informed patient only in a center with expertise in interpreting imaging studies, evaluating lung nodules, and diagnosing and treating lung cancer. We do not recommend that CT screening be done at the neighborhood shopping mall or medical facility without the appropriate expertise to pursue the results and maximize the benefits of this testing (30, 31).
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Steven, Walerstein, MD, President of the New York chapter of the American College of Physicians, Dr. Alan Multz, Dr. Vladimir Gotlieb, Nassau University Medical Center, Department of Medicine, Division of Hematology and Oncology.
October 25, 2011
Financial Logistics Still Loom Large
Articles "Screening for Lung cancer: for patients at increased risk for lung cancer, it works" and Screening for lung cancer: it works, but does it really work?" published in the journal recently 4,5 , is a commendable effort, though the question about financial logistics still looms large pending "official" recommendations. Financial consequences of such screening modality would stimulate extensive debates within medical and non-medical communities, before it becomes a standard of care.
We at Nassau University Medical Center conducted a study which found that hospitals with poor catchment areas diagnose significantly more people with Stage 4 lung cancer and less people in Stage 1 as compared to national average and to the hospitals with richer catchment areas 1 ,2 .
NUMC vs. NSR
NUMC vs. LIJ
NUMC vs. US
NUMC- Nassau University Medical center, NSR- North Shore University Hospital, Long Island
Numbers in parenthesis are the number patients in the series.
We are currently looking into how to address this disparity.
The National Lung Screening Trial 3 as well as the articles published in Annals 4 ,5 are interesting because of what we found. If there is a question about making this screening into a universal recommendation due to financial reasons, it would be prudent to include hospitals caring for a larger percentage of lower socioeconomic patients as well as those of a more "insured" payer mix.
There are currently about 150,000 deaths recorded in the United States related to Lung cancer. High proportion of them are diagnosed in advanced stages and started on the treatment with knowingly low expected survival at 5 year mark. These numbers have been unchanged for the last 10 years. Advances in chemotherapy for lung cancer have lead to very small survival benefits. These facts clearly justify more aggressive approach to screening for this deadly condition with the goal of detecting it in the lower stages especially in the higher risk categories.
We think this would go a long way in mitigating the disparity in the stages of lung cancer found in our study.
Dr. Steven Walerstein, President of the New York chapter of the American College of Physicians
Dr. Alan Multz, Dr. Vladimir Gotlieb, Nassau University Medical Center, Department of Medicine, Division of Hematology and Oncology.
1. Gotlieb V., Verma V, Fogel J., Multz A, Gralla R. Poster presentation. Abstract #6037 2011 Annual ASCO meeting. Comparative analysis of lung cancer in a public hospital versus private hospitals in New York City metropolitan area.
2. The International Early Cancer Action Program Investigators: Survival of Patients with Stage I Lung Cancer Detected on CT Screening. N Eng J Med 2006; 355(17):1763-1771
3. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. NEJM, June 29, 2011.
4. Jett J and Midthun D. Screening for Lung Cancer: For Patients at increased Risk for Lung Cancer, It Works. Annals of Internal Medicine, October 18, 2011:540-542. 5. Silvestri G. Screening for Lung Cancer: it works, but does it really work? Annals of Internal Medicine, October 18, 2011:537-540. Conflict of Interest:
Frederic W., Grannis, Jr., MD
October 28, 2011
Disagree With Author's Advice
The pro/con debate in the pages of the Annals of Internal Medicine between Gerard Silvestri and James Jett on whether an otherwise healthy, high-risk individual should be offered computerized tomographic screening for lung cancer (LCS) is of particular interest because both individuals were authors on the Second American College of Chest Physicians (ACCP) Guideline which recommended against such screening. I have commented elsewhere on what I perceived as major problems with this guideline.
Dr. Jett has now revised his stance on LCS and answers "Yes" that he would recommend screening, with appropriate discussion of potential benefits and risks. This change is presumably in response to his analysis of the randomized controlled trial evidence of a minimum 20% mortality reduction in the National Lung Screen Trial as well as the estimated 28% reduction in mortality in his own Mayo LCS study.
Dr. Silvestri, however, has not altered his "No" recommendation, despite the availability of a wealth of data published since release of the ACCP guideline. He appears to base his advice partly upon risks of needle biopsies recently published by the White River Junction VA Hospital epidemiologists, in which multiple deaths were reported following SEER registry transthoracic needle biopsies. What Silvestri fails to inform his readers is that none of these needle biopsy deaths were in the context of LCS and that most deaths were in patients who were already sufficiently ill to be hospitalized before diagnostic biopsies had been performed. To the best of my knowledge, there is not a single published report of a fatal complication following a needle biopsy of a benign nodule found in LCS studies reporting on more than one hundred thousand individuals.
With the understanding that there are approximately 500,000 individuals with lung cancers 2 mm. and larger, detectable by CT scan in the U.S. at this moment in time, that a minimum of 85% will die in the absence of screening that a minimum of 20% of these deaths would be prevented following CT detection, and that the NLST study found no unanticipated risks, I disagree with Silvestri's advice that the patient to "run as far and as fast away from a CT scanner as she can get". It was irresponsible for the editors of the Annals to have published this recommendation.
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5. Jett JR, Midthun DE, Swensen SJ. Screening for lung cancer with low-dose spiral CT scan of the chest and sputum cytology. Pulm Perspect 1999;16:1-3.
6. McMahon PM, Kong CY, Johnson BE, Weinstein MC, Weeks JC, Kuntz KM, et al. Estimating long-term effectiveness of lung cancer screening in the Mayo CT screening study. Radiology. 2008;248:278-87. [PMID: 18458247]
7. McMahon PM, Kong CY, Weinstein MC, Tramontano AC, Cipriano LE, Johnson BE, et al. Adopting helical CT screening for lung cancer: potential health consequences during a 15-year period. Cancer. 2008;113:3440-9. [PMID: 18988293]
8.Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann Intern Med. 2011;155:137-44. [PMID: 21810706]
9. Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin. 2001;51:15-36. [PMID: 11577478]
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