1. Early Detection and Screening for Lung Cancer
Josephine Mak
Registrar
Waikato Cardiothoracic Unit

2. Lung Cancer
Lung Ca = one of the leading causes of cancer related deaths
NZ’s biggest cancer killer with more than 1600 deaths each year
In 2013 more than 2000 diagnosed and 1600 deaths (NZ)
Disease of older populations
Most common cause of cancer death for men and women 65-74, and men (NZ)
Worldwide ~1.59million deaths in 2012
85-90% of all lung Ca thought to be caused by smoking / passive smoking
1 in 5 diagnosed thought never smoked
Second hand exposure / environmental smoke attributed to significant amount of lung Ca in non smokers
High percentage of lung Ca occurs in former smokers as risk for Lung Ca does not decline for many years
Lungfoundation.org.nz/lunghealth
New Zealand Ministry of Health website
UptoDate

3. Lung Cancer Small cell carcinomas Non small cell lung carcinoma
20% of primary lung Ca
Highly responsive to chemotherapy
Usually disseminated at presentation
Primarily non operative mx (although relapse generally within 1yr)
Non small cell lung carcinoma
80% of primary lung Ca
Adenocarcinoma, Squamous cell carcinoma, large cell carcinoma
Poorly responsive to Chemo -> Tx locally with surgery/Radiation
Smoking = primary cause of ALL histologies of primary lung cancer

4. To Screen or not to screen?
Currently no routine screening for lung Ca in the world
However not for lack of trying over the years – since 1960s.
Recent developments over past 15 yrs
Early detection / treatment an appealing idea
Identify lung cancers at an early stage, before signs and symptoms develop, to increase the number of patients who are eligible for curative surgical resection, to improve overall survival and resource utilization.

5. Lung Cancer Early stage lung ca is asymptomatic
the majority of patients present with symptoms because of advanced local or metastatic disease when it is unlikely curative
16% localised disease | 5yr survival 49%
37% regional disease | 5yr survival 16%
39% advanced disease | 5yr survival 2% [8% unstaged ]
5-yr survival rates approximately 18% for all individuals with lung Ca
Lungfoundation.org.nz/lunghealth

6. screening
“a public health service in which members of a defined population, who do not necessarily perceive they are at risk of, or are already affected by a disease or its complications, are asked a question or offered a test, to identify those individuals who are more likely to be helped than harmed by further tests or treatment to reduce the risk of a disease or its complications”
(UK National Screening Committee)

7. NOT just the test itself Screening involves a whole programme

8. WHO “Classic” Wilson and JUNGER criteria
The condition sought should be an important health problem
There should be an accepted treatment for patients with recognized disease.
Facilities for diagnosis and treatment should be available.
There should be a recognizable latent or early symptomatic stage.
There should be a suitable test or examination.
The test should be acceptable to the population.
The natural history of the condition, including development from latent to declared disease, should be adequately understood.
There should be an agreed policy on whom to treat as patients.
The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole.
Case-finding should be a continuing process and not a “once and for all” project.

9. WHO “Emerging” Screening Criteria
The screening programme should respond to a recognized need.
The objectives of screening should be defined at the outset. 
There should be a defined target population. 
There should be scientific evidence of screening programme effectiveness. 
The programme should integrate education, testing, clinical services and programme management. 
There should be quality assurance, with mechanisms to minimize potential risks of screening. 
The programme should ensure informed choice, confidentiality and respect for autonomy.
The programme should promote equity and access to screening for the entire target population. 
Programme evaluation should be planned from the outset. 
The overall benefits of screening should outweigh the harm. 

10. To Screen or not to screen?
Lung ca has characteristics which suggest screening should be effective
High morbidity and mortality
Significant prevalence
Long ‘latent’ stage
Treatment more effective in early stage disease
Clinical outcomes (for NSCLC) directly related to stage at diagnosis
Within Stage I NSCLC there is a relationship between tumour size and survival
Aim of screening would be to increase overall cure rate and allow more limited surgical resection
Requires MDT programme to ensure screening properly performed, results properly interpreted and followed up, and detected disease is managed properly

11. To Screen or not to screen?
Need to consider possible harms
Consequences of evaluating abnormal findings
Cost eg. of investigations, treatment, follow up
Associated morbidity eg. with needle biopsy and surgery
National lung screening trial – high risk individuals screened – of abnormal results (24.2% of LDCT and 6.9% CXR), 96% were false positives!
Radiation exposure
Serial imaging independently increasing cancer risk – cumulative radiation dose
Patient distress
Overdiagnosis
Lead time bias

12. Guidelines
Guidelines have only changed within the past 5 years to recommend screening for lung Ca in certain groups of high risk patients
Due to advent of low dose CT
Prior to that:
US Preventative Services Task Force gave ‘D’ recommendations in 1985 and 1996 ie “recommend against routinely providing [the service]. The USPSTF found at least fair evidence that [the service is ineffective] or that harms outweigh benefits”.
This changed in 2004 to ‘I’
Insufficient evidence to recommend for or against routine screening. Evidence that screening is effective is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.”
Changed again in 2013 to ‘B’

13. Guidelines

14. CXR and Sputum
First mass-screening project was conducted in London
No study has ever shown mortality benefit
At least seven large scale controlled clinical trials
Six randomised, one non randomised
Four large scale studies

17. PLCO (Prostate, Lung, Cervical, Ovarian)
US study – 10 centres
154 934 participants - 77 464 in intervention arm
Men and women, ages 55 to 74 years, were randomly assigned to undergo either an annual CXR for 3 years (smokers) or 2 years (nonsmokers) or routine medical care (unscreened group).
The trial was designed to determine whether a smaller mortality benefi t might be found with CXR screening, 89% power to detect a 10% reduction in lung cancer– specific mortality.
Started in 1993, expected to be completed in 2014 but stopped early in 2010
Technology outdated + no benefit

18. Low Dose CT Possible because of improving technologies
Non contrast study obtained using multidetector CT scanner during a single maximal inspiratory breath hold
Scanning time 25 seconds
High resolution (1.0 – 2.5mm interval images)
7 trials – one good, three fair
ONE trial demonstrating mortality benefit
Other trials too small, or still preliminary, or o

19. National Lung Screening Trial
33 US medical centres - 53,454 current or former heavy smokers
High risk patient population
Men and women 55-74yrs with at least 30 packs years of smoking
Included current smokers and those who had discontinued smoking within 15yrs of enrolment
Compared annual screening by LDCT scanning vs CXR for three years
Positive findings
Non calcified nodule >= 4mm on LDCT or any non calcified nodule on CXR

20. National Lung Screening Trial
Trial stopped early after interim analysis showed statistically significant benefit for LDCT scanning
Median follow up of 6.5yrs
645 cases of lung cancer per 100,000 person years (1060 cancers) in the LDCT group and 572 cases per 100,000 person years (941 cancers) in CXR group = incidence rate ratio of 1.13 (95% CI 1.03 – 1.23)
247 lung cancer deaths in CT group and 309 in CXR group per 100,000 person years, giving a relative mortality reduction of 20% and an absolute reduction of 62 lung cancer deaths per 100,000 years
6.7% relative reduction in all cause mortality and absolute reduction of 74 deaths to 100,000 person years

21. National Lung Screening Trial
Over 3 screening rounds, 24.1 of LDT scans and 6.9% of all CXR were abnormal
High cumulative false positive rate
96.4% LDCT
94.5% CXR
Follow up as per each institution
90.4% of LDCT and 92.7% of CXR false-positive screens led to at least one diagnostic procedure – mostly imaging
297 patients in LDCT cohort and 121 who had CXR had surgery

22. Other Trials
Nelson trial – RCT in Netherlands and Belgium. LDCT screening at increasing interval lengths (1, 2, 2.5yrs) compared to no screening in 15,822 current or former smokers.
Dante Trial – RCT in Italy comparing 2472 male smokers aged – designed to assess lung cancer specific mortality over 10 years. Compared 5yrs of annual screening by single slice spiral LDCT scan vs annual clinic follow up. numbers of advanced lung cancer cases and lung cancer mortality the same (543 versus 544 per 100,000 person-years) – small trial size.
DLCST (Danish) RCT – 4104 smokers (at least 20 pack years) aged Long-term results from the DLCST show no difference in lung cancer-specific or overall mortality – although lower risk population
MILD (Multicentric Italian Lung Detection) - compared annual or biennial LDCT screening with no screening in 4099 smokers (>20 pack-years, current or quit within 10 years) age 49 years or older. No difference in lung cancer mortality. Poor trial.

23. Conclusion
Need more evidence but LDCT for a select population seems to how mortality benefit
LDCT is significantly more sensitive than CXR for identifying small asymptomatic lung Ca
CXR does not reduced mortality in lung ca
HIGH RATE of false positives – most common incidental findings being emphysema and coronary artery calcifications
Cost effectiveness – given high false positives
Screening does not replace public health efforts targeted at prevention

24. references Lungfoundation.org.nz/lunghealth
New Zealand Ministry of Health website
UptoDate - cancer?source=search_result&search=screening%20for%20lung%20cancer&selectedTitle=1~150
guidelines/lung-cancer-screening-guidelines.html
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