1. General Internal Medicine Grand Rounds Dave Tanaka October 30, 2012
Should we recommend low dose computerized tomography of the chest to screen for lung cancer
General Internal Medicine Grand Rounds
Dave Tanaka
October 30, 2012

2. Objectives Review previous data on lung cancer screening
Review the National Lung Screening Trial
Review current recommendations for lung cancer screening
Each clinician should have “Talking points” for patient discussions

3. Lung Cancer Facts
Lung cancer is the leading cause of cancer death in US (worldwide)
The American Cancer society estimates that there will be 226,160 new cases of lung cancer and 160,340 deaths in US is 2012
Most lung cancer is diagnosed at advanced stage (40% stage IV, 30% III)
5 year survival 16%

4. Questions How many have had patients request lung cancer screening?
How many have offered chest xrays as lung cancer screening?
How many have offered chest CT scanning for lung cancer screening?

5. Lung Cancer screening practices of primary care physicians: results form a national survey
national survey, 962 responses, 38% no lung cancer screening, 55% had ordered CXR, 22% LDCT and <5% cytology
25% believed an expert group recommends lung cancer screening
The factors that predict ordering of lung cancer screening: belief that experts recommend it or that screening tests are effective, if they would recommend screening for asymptomatic, non-smokers and if their patients had asked them about screening.

9. Chest xrays 4 RTC 6,300-11,000 patients, 1970-1980’s
No difference in lung cancer mortality in the screening groups vs controls (this compared more frequent CXR’s because CXR was often used on regular basis for smokers)
There were increased numbers of lung cancers found in the screened group (over diagnosis)

10. PLCO study
RTC 154, age 55-74
CXR at baseline then 3 annual screens vs usual care
F/U to max 13 years
10% current smokers, 42% previous smokers, 11% with 1st degree relative with lung cancer
CXR screened lung cancer mortality 0.99 ( ) vs usual care

11. PLCO study (NLST eligible)
CXR 15,183 vs usual care 15,138
CXR 60.9% male vs usual care 60.2%
CXR 52.0 pack yrs vs usual care 52.5 pack yrs
Lung cancer incidence (per 100,000 person-yrs) CXR 606 vs usual care 608 (RR )
Lung cancer mortality CXR 361 vs usual care 383 (RR )

12. PLCO study conclusions
No benefit from CXR screening in lung cancer mortality vs usual care
Subanalysis (NLST eligible) – no benefit from CXR screening in lung cancer mortality at 6 years (no difference at 13 years)

13. National Lung Screening Trial
RTC 53,434 8/2002-4/ US MedCen
Age 55-74, smoked > 30 pack-yrs, quit within past 15 years
Exclusions: previous diagnosis of lung cancer, hemoptysis or unexplained weight loss > 6.8 kg (15 lbs) in preceding year

14. NLST Randomized to LDCT scan (26,722) vs CXR (26,732)
3 screening studies, T0, T1, T2 done at 1 year intervals
Positive result defined as > 4mm non-calcified nodule

15. Results T0 T1 T2 Total Positive False Positive CT scan 27.3% 27.9%
16.8%
39.1%
96.4%
CXR
9.2%
6.2%
5.0%
16.0%
94.5%

16. Adverse Events
Complications after diagnostic evaluation procedure after positive screening test CT scan 1.4% CXR 1.6% Major complications after diagnostic evaluation CT scan lung cancer % % CXR lung cancer + 8.2% %
There were 16 deaths (10 with lung cancer) in CT scan group within 60 days of diagnostic procedure
There were 10 deaths (10 with lung cancer) in the CXR group within 60 days of diagnostic procedure

17. Lung Cancer CT scan 1060 645 / 100,000 CXR 941 572 / 100,000
Ave NLST participant had 2% risk of lung cancer per year

18. Lung Cancer Mortality
CT scan / 100, % CXR / 100, % Absolute difference of 0.3% For every 1,000 screened there will be 14 lung cancer deaths after 3 yearly CT scans and total time of 6.5 years, 3 lung cancer deaths will be averted.

20. The Role of Computed Tomography (CT) Screening for Lung Cancer
Recommendations from the American College of Chest Physicians and the American Society of Clinical Oncology

21. Recommendations
Note: Grade of recommendations based on modified GRADE approach (

22. Recommendation 1
For smokers and former smokers who are age 55 to 74 and who have smoked for 30 pack years or more and either continue to smoke or have quit within the past 15 years, we suggest that annual screening with low-dose CT should be offered over both annual screening with chest radiograph or no screening, but only in settings that can deliver the comprehensive care provided to NLST participants.
Grade of recommendation: 2B
Note: Pack year = the number of packs of cigarettes smoked per day multiplied by the number of years a person has smoked

23. Remarks for Recommendation 1
Remark 1: Counseling should include a complete description of potential benefits and harms, as outlined the guideline (online), so the individual can decide whether or not to undergo LDCT screening.
Remark 2: Screening should be conducted in a center similar to those where the NLST was conducted, with multi-disciplinary coordinated care and a comprehensive process for screening, image interpretation, management of findings, and evaluation and treatment of potential cancers.
Continued on next slide

24. Remarks for Recommendation 1, cont’d
Remark 3: A number of important questions about screening could be addressed if individuals who are screened for lung cancer are entered into a registry that captures data on follow-up testing, radiation exposure, patient experience, and smoking behavior.
Remark 4: Quality metrics should be developed such as those in use for mammography screening, which could help enhance the benefits and minimize the harm for individuals who undergo screening.
Continued on next slide

25. Remarks for Recommendation 1, cont’d
Remark 5: Screening for lung cancer is not a substitute for stopping smoking. The most important thing patients can do to prevent lung cancer is not smoke.
Remark 6: The most effective duration or frequency of screening is not known.

26. Recommendation 2
For individuals who have accumulated fewer than 30 pack years of smoking or are either younger than age 55 or older than 74, or individuals who quit smoking more than 15 years ago, and for individuals with severe comorbidities that would preclude potentially curative treatment and/or limit life expectancy, we suggest that CT screening should not be performed.
Grade of recommendation: 2C

27. Clinician-Patient Communication
Quantify the potential benefits
Quantify the potential harms
Emphasize smoking cessation
Point to useful tools on smoking cessation, risk of radiation exposure and calculating lung cancer risk

28. Future Directions/Research
Outstanding questions/suggested research
Generalizability of reported findings
Comparison of limited # of annual screenings to potentially higher # of annual screenings
Optimum screening schedule
Cost-effectiveness studies
Randomized trials with participants of different ages and smoking histories than in the NLST and in settings unlike those in previous studies

29. How NLST might apply to a patient
Estimates are based on 2 models, one that predicts the chance of dying from lung cancer in a year and the other that predicts the chance of dying from other causes in a year.
The models considered the person’s age, sex, smoking history and exposure to asbsetos. Both models have been studied the lung cancer (validated) and other (under predicted)

30. Average NLST patient 62 yo male current smoker, 1.5 ppd for 35 years
Deaths from lung cancer (without screening) per 1000 person
Deaths from lung cancer (with screening) per 1000 persons
Deaths averted per
Persons needed to be screened for 3 y to prevent 1 death from lung cancer over 6 years

31. Min eligible NLST participant
55 yo female former smoker 1 ppd for 30 years, who just quit
Deaths from lung cancer (without screening) per 1000 person
Deaths from lung cancer (with screening) per 1000 persons 3.2
Deaths averted per
Persons needed to be screened for 3 y to prevent 1 death from lung cancer over 6 years

32. High-risk NLST participant
70 yo current 2 ppd smoker for 55 years
Deaths from lung cancer (without screening) per 1000 person
Deaths from lung cancer (with screening) per 1000 persons
Deaths averted per
Persons needed to be screened for 3 y to prevent 1 death from lung cancer over 6 years - 82

33. Min eligible participant by NCCN guidelines
50 yo male former smoker 1 ppd for 20 years, who quit 10 years ago with an occupational asbestos exposure history
Deaths from lung cancer (without screening) per 1000 person
Deaths from lung cancer (with screening) per 1000 persons 1.3
Deaths averted per
Persons needed to be screened for 3 y to prevent 1 death from lung cancer over 6 years

34. Low risk eligible participant for Sequoia Hospital lung screening
40 yo female former smoker 1 ppd for 10 years, who quit 15 years ago
Deaths from lung cancer (without screening) per 1000 person
Deaths from lung cancer (with screening) per 1000 persons
Deaths averted per
Persons needed to be screened for 3 y to prevent 1 death from lung cancer over 6 years

35. Harms of LDCT for lung cancer screening
Detection of abnormalities
In review of RTC and cohort studies the average detection of lung nodules was 20%
More than 90% were false positives
In NLST, 1.2% of patients not found to have lung cancer underwent invasive procedure and 0.7% had thoracoscopy, mediatinoscopy or thoracotomy

36. Adverse Events
Complications after diagnostic evaluation procedure after positive screening test CT scan 1.4% CXR 1.6% Major complications after diagnostic evaluation CT scan lung cancer % % CXR lung cancer + 8.2% %
There were 16 deaths (10 with lung cancer) in CT scan group within 60 days of diagnostic procedure
There were 10 deaths (10 with lung cancer) in the CXR group within 60 days of diagnostic procedure

37. Harms of LDCT for lung cancer screening
Overdiagnosis
Previous studies suggest that CXR may have an overdiagnosis rate of 25%
NLST show 120 excess lung cancers in the CT scan group vs CXR but further f/u is necessary

38. Harms of LDCT for lung cancer screening
Radiation exposure
LDCT 1.5 mSv per exam
Diagnostic chest CT 8 mSv, Chest CT/PET 14 mSv
Average NLST patient received 8 mSv over 3 years (screens (3) + diagnostic) and it is estimated that will cause 1 death from cancer per 2500 persons screened
Preliminary modeling potential risks may vastly outweigh benefits for nonsmokers or thos <42 years of age.

39. Harms of LDCT for lung cancer screening
Quality of Life
CT scan screening 88-91% reported on discomfort but 46% reported psychological distress while awaiting the results
There may be QOL benefits from lower morbidity from advanced lung cancer but there are also potential harms due to anxiety, cost and harms from diagnostic tests for false positive scans and overdiagnosed cancers

40. Other considerations
The operative mortality for lung cancer surgery in NLST was 1% in CT scan and 0.2% in CXR. This compares to 4% operative mortality seen in general population study.
Cost effective analysis is planned and is pending

41. Other considerations
Will populations with a different risk profile than NLST benefit?
Are less frequent screening regimens effective?
How long should screening continue?
Would a different criteria for a positive scan provide the same benefit but at less risk of false positive / lower cost?

42. Conclusions There is no benefit from CXR screening for lung cancer
The NLST demonstrates a lung cancer mortality benefit with 3 yearly LDCT scans and an average f/u of 6.5 years. The absolute benefit is 0.3% or 1 averted death / 320 screened
The average rate of positive scans is 20% (90+% are false positives)

43. Conclusions
The risk of major complication seen in NLST for patients not diagnosed with lung cancer undergoing diagnostic procedure is 0.06%
The risk from radiation estimated for the average NLST participant (8mSv) is 1 cancer death per 2500 participants

44. My recommendation
If after discussion of risks and benefits, I would only offer LDCT screening for individuals that meet the NLST eligibility criteria – age 55-74, smoking at least 30 pack-years, quit within previous 15 years. I would recommend LDCT for no more than 3 years.

45. Introduction & Context
High mortality associated with lung cancer
Most diagnoses occur at later stages
Prior to screening with low-dose computed tomography (LDCT), no evidence that screening strategies decreased lung cancer mortality risk
National Lung Screening Trial (NLST) – first randomized controlled trial (RCT) to show a screening benefit in people with a history of heavy smoking (e.g. smoking 1 pack a day for 30 years or 2 packs a day for 15 years)
All screening technologies carry potential benefits and potential harms

46. Guideline Methodology: Systematic Review
Guideline based on a systematic review by the American Cancer Society, American College of Chest Physicians, American Society for Clinical Oncology and National Comprehensive Cancer Network
An Expert Panel reviewed relevant medical literature
Databases searched and data parameters
MEDLINE: April 2012
EMBASE: April 2012
Cochrane Collaboration Library: April 2012
Evidence base: Eight RCTs and thirteen cohort studies in which all subjects were screened with LDCT

47. Clinical Questions
Key Question 1: What are the potential benefits of screening individuals at elevated risk of developing lung cancer using LDCT?
Key Question 2: What are the potential harms of screening individuals at elevated risk of developing lung cancer using LDCT?
Key Question 3: Which groups are most likely to benefit or not benefit from screening?
Key Question 4: In what setting is screening likely to be effective?
Abbreviations: LDCT, low-dose computed tomography

48. Summary of the Evidence
1. The National Lung Screening Trial (NLST), a large, high quality randomized controlled study demonstrated that among adults between the ages of who smoked at least 30 pack years, including former smokers who quit within 15 years, annual screening with low-dose CT for 3 consecutive years reduced the absolute risk of lung cancer death by 0.33% when compared to annual screening with chest radiography. (continued on next slide)

49. Summary of the Evidence, cont’d
1 (cont’d). This translates to 3 fewer deaths from lung cancer for every 1,000 high-risk individuals who undergo CT screening rather than screening with chest radiography and a 20% relative risk reduction. This mortality reduction was observed over a median follow up of 78 months. Another smaller randomized controlled trial of CT screening did not find a benefit when compared with no screening.

50. Summary of the Evidence, cont’d
2. Multiple studies have shown that screening with low-dose CT finds lung nodules in about 180 of every 1,000 individuals who undergo screening. While 95% of these nodules ultimately prove not to be cancerous, their evaluation typically involves repeat CT scanning, and sometimes requires the use of invasive procedures, including surgery. Invasive procedures carry risks, including rarely, major complications and even death.

51. Summary of the Evidence, cont’d
3. The reported outcomes for CT screening have been achieved in selected, high-risk, motivated study volunteers who underwent screening at centers with experience in imaging, diagnosis and treatment, using an organized process of scanning, scan interpretation and nodule evaluation. Application of CT screening to lower risk groups or outside of these settings may alter the balance of observed benefits and harms unfavorably.

52. Summary of the Evidence, cont’d
4. The reported benefit of CT screening is primarily from a study that compared LDCT screening to chest x-ray screening rather than no screening. Studies have not found a benefit of chest x-ray screening. 5. Extrapolated estimates suggest that the magnitude of the harm from radiation delivered by low-dose CT screening is smaller than the estimated benefit of screening individuals such as those screened in the NLST for lung cancer.