The Evidence for Lung Cancer Screening

Why Screen for Lung Cancer?

The purpose of screening is to prevent or delay, by means of earlier detection, the development of advanced disease and its adverse effects. Approximately 35,000 new cases of lung cancer are diagnosed in the United Kingdom each year. Approximately 90% of these patients will die as a result of the disease over the course of the next year.

Lung cancer is the most common cause of cancer death in men and women both in the United Kingdom and worldwide. In the UK:

lung cancer accounts for over 30% of cancer deaths in men and 25% of cancer deaths in women
more women die as a result of lung cancer than breast cancer
the number of deaths from lung cancer exceeds the total number of deaths from breast, colon, prostate, and cervical cancer put together

Overall survival for lung cancer is very poor- over the past 20 years five-year survival has remained static at around 7%. This compares poorly with the rest of the developed World and is largely because most patients present with advanced disease at the time of presentation.

Although most lung cancer occurs in ex and current smokers, approximately 15% occur in individuals who have never smoked. Lung cancer continues to be underfunded for research and early detection, primarily because it is viewed as a “self-inflicted” disease that could be virtually eliminated if no one smoked. While tobacco cessation is critical to reducing lung cancer incidence and this strategy is strongly supported by Lifescan, stopping smoking alone cannot effect either the prevalence of lung cancer among former and never smokers or the very high mortality rate of newly diagnosed lung cancer patients whether they smoked or not.

The limited number of survivors, coupled with the stigmatization of smokers and the vast size of the at-risk population undermines efforts to support a change in public health policy, which could lead to substantive improvements in lung cancer outcomes.

Screening is a method of detecting a disease such as cancer before clinical signs or symptoms become evident. Early stage cancers can be more easily treated with a curative outcome than later stage cancers. Once a cancer has spread to other organs (metastasized) that cancer is rarely cured

CT lung scanning is highly cost effective for high-risk individuals

Treatment for stage 1 cancer is less than half the cost of late-stage treatment. If treating cancer early is cheaper than treating it later, it stands to reason that the more sensitive and accurate the screening tool, the more cost effective it will be.
This position has been confirmed by the ELCAP study which found “CT screening for lung cancer to be highly cost effective.” The authors also reported that other estimates of the cost-effectiveness of CT scanning for lung cancer for various risk profiles are similar or better than that for mammography- a screening system already in use.
Other studies have reached similar conclusions. For example, Wisnifesky et al evaluated the cost-effectiveness of a single baseline CT for lung cancer scanning in high-risk individuals by incorporating ELCAP data into a decision analysis model, comparing it to observation without scanning. The study concluded that “a baseline low-dose CT scan for lung cancer is potentially highly cost-effective and compares favourably to the cost-effectiveness in other screening programs.”
In support of the available evidence-base, Lifescan believes that targeting groups most at risk of lung cancer will yield the maximum clinical and cost benefits.
Eighty-five per cent of lung cancer occurs as a result of smoking and its incidence rises steeply in those aged over 40. For this reason we offer CT scans to individuals over the age of 40 with a family history, occupational exposure or a significant smoking history. We define a ‘significant smoking history’ as smokers or ex-smokers (who have smoked the equivalent of one pack a day for ten years) and passive smokers. Individuals who have been exposed to asbestos or who have suffered some other known occupational exposure are also considered to be at risk.
For those over the age of 40 with a history of smoking or occupational exposure, Lifescan recommends annual examination until the individual’s risk of lung cancer is reduced to the equivalent of a non-smoker. This risk reduction occurs when no nodules have been detected by the time the individual reaches 75 years of age, or 20 years after giving up smoking. Annual screening is recommended until this point, because a cancerous nodule can develop within twelve months.

Lung cancer screening studies

On November 4, 2010, the National Cancer Institute (NCI) in the US announced that its eight year trial of CT screening for lung cancer indicated that CT screening for lung cancer does reduce the number of lung cancer deaths in a high risk population.

The National Lung Screening Trial (NLST) launched by the National Cancer Institute in 2002 recruited 53,000 people, 55 or older, who were at high risk for lung cancer because of their smoking history, and who were otherwise healthy and had no symptoms of lung cancer to receive a chest x-ray or a CT scan. The trial was terminated early when the collected data indicated that those receiving the CT scan had 20% fewer deaths from lung cancer than those receiving a chest x-ray. Deaths from all other causes were also 7% lower in the CT arm, indicating that CT scans may also be of benefit in the early detection of other diseases as well. The full results from this – the largest and most rigorous trial to date are expected to be published later this year. The results from this trial will add to the case already well made by previous non randomized studies (below) for lung cancer screening of at risk individuals.

1. Early Lung Cancer Action Project (ELCAP)

Early lung cancer action project: overall design and findings from baseline screening.
Henschke CI, et al.
Lancet 1999. 354: 99-105:

2. Survival of Patients with Stage I Lung Cancer Detected on CT Screening

The International Early Lung Cancer Action Program Investigators*
N Engl J Med 2006;355:1763-71.

Results:
Screening resulted in a diagnosis of lung cancer in 484 participants. Of these participants,
412 (85%) had clinical stage I lung cancer, and the estimated 10-year survival
rate was 88% in this subgroup (95% confidence interval [CI], 84 to 91). Among
the 302 participants with clinical stage I cancer who underwent surgical resection
within 1 month after diagnosis, the survival rate was 92% (95% CI, 88 to 95). The
8 participants with clinical stage I cancer who did not receive treatment died within 5 years after diagnosis.

3. Anti-lung Cancer Association Study (ALCA)

Computed tomography screening for lung carcinoma in Japan.
Kanedo M, et al
Cancer 2000; 89 (11 Suppl):2485-8

ALCA is a Japanese for-profit organization established in 1975 for screening lung cancer. Ninety-two percent of members enrolled in the service are heavy smokers with a mean age of about 60 years. In September 1993, ALCA introduced low-dose spiral CT screening to detect lung cancer in its early stages. As part of their evaluation, patients underwent low dose CT screening. 22 Patients out of a population of 1,443 persons who underwent screening were diagnosed with lung cancer. CXR failed to detect 73% of cancers detected on low dose helical CT.

4. Association Between Lung Cancer Incidence and Family History of Lung Cancer.

Data From a Large-Scale Population-Based Cohort Study, the JPHC Study

Jun-ichi Nitadori, MD, Manami Inoue, MD, PhD, Motoki Iwasaki, MD, PhD, Tetsuya Otani, MD, PhD, Shizuka Sasazuki, MD, PhD, Kanji Nagai, MD, PhD, Shoichiro Tsugane, MD, PhD and the JPHC Study Group †

Conclusions:
These results suggest that those with a family history of lung cancer are more likely to acquire lung cancer themselves.

5. Lung Cancer Screening With Low-Dose Computed Tomography: Canadian Experience

Heidi C Roberts, MD; Demetris Patsios,MD; Narinder S Paul, MD; Maureen McGregor;
Gordon Weisbrod, MD; TaeBong Chung, MD; Steven Herman, MD; Scott Boerner, MD;
Thomas Waddell, MD; Shafique Keshavjee, MD; Gail Darling, MD; Andre Pereira, MD;
Ashwini Kale, MD; Hamid Bayanati, MD; Igor Sitartchouk, PhD; Ming Tsao, MD;
Frances A Shepherd, MD
Can Assoc Radiol J 2007;58(4):225–235.

Conclusion:
Our results confirm that LDCT identifies small, early-stage, resectable lung cancer
in a high-risk population.

6. The Danish Randomized Lung Cancer CT Screening Trial -Overall Design and Results of the Prevalence Round

Journal of Thoracic Oncology • Volume 4, Number 5, May 2009

Introduction:
Lung cancer screening with low dose computed tomography (CT) has not yet been evaluated in randomized clinical trials, although several are underway.

Methods:
In The Danish Lung Cancer Screening Trial, 4104 smokers and previous smokers from 2004 to 2006 were randomized to either screening with annual low dose CT scans for 5 years or no screening. A history of cigarette smoking of at least 20 pack years was required. All participants have annual lung function tests, and questionnaires regarding health status, psychosocial consequences of screening, smoking habits, and smoking cessation.
Baseline CT scans were performed in 2052 participants.
Pulmonary nodules were classified according to size and morphology:
(1) Nodules smaller than 5 mm and calcified (benign) nodules
were tabulated, (2) Noncalcified nodules between 5 and 15 mm were rescanned after 3 months. If the nodule increased in size or was larger than 15 mm the participant was referred for diagnostic
workup.

Results:
At baseline 179 persons showed noncalcified nodules larger than 5 mm, and most were rescanned after 3 months: The rate of false-positive diagnoses was 7.9%, and 17 individuals (0.8%) turned out to have lung cancer. Ten of these had stage I disease.
Eleven of 17 lung cancers at baseline were treated surgically, eight of these by video assisted thoracic surgery resection.

7. The Cost-Effectiveness of Low-Dose CT Screening for Lung Cancer Preliminary Results of Baseline Screening.

Wisnifesky et al.
Chest, 2003; 124: 614-621

Conclusions:
A baseline low-dose CT scan for lung cancer screening is potentially highly
cost-effective and compares favorably to the cost-effectiveness ratios of other screening
programs.

Meanwhile in the UK

Stories from BBC NEWS:

Lung cancer screening trial hope - December 2008
http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/7798691.stm

Researchers have taken a step towards starting a national lung cancer screening programme.
The government-backed Liverpool University team want to test using CT scans to detect early disease in those who have not yet developed symptoms.

Professor Mike Richards, National Clinical Director for Cancer welcomed the research.
"Lung cancer remains the leading cause of death from cancer."
"Methods to detect the disease early, at a stage when it is curable, are urgently needed, alongside efforts to prevent the disease by reducing smoking."

Drive to up UK lung cancer survival - November 2007
http://news.bbc.co.uk/1/hi/health/7074870.stm

Leading experts have called for a push to double lung cancer survival rates in the UK over the next decade.
The UK Lung Cancer Coalition has put together a 12-point plan for better detection and treatment as well as more funding for research.

Development of screening programmes, better funding of research, earlier diagnosis and greater equity of access to lung cancer specialists would all improve survival rates, they added.

A Department of Health spokesperson said: "We accept that further improvements in cancer services are needed to continue to reduce the gap between us and the rest of northern and western Europe.

"Poor survival rates in England can be attributed mainly to patients having more advanced disease at diagnosis than patients in other European countries.

Are there any risks from the radiation?

Imaging procedures are useful clinical tools that can help identify and manage disease, but they also carry health risks. It is important for a patient to understand the trade-off between the potential benefits of an imaging procedure and the potential risks and to discuss the balance between potential benefits and risks with their physician. As a general rule, no imaging procedure should be done without good cause or at any higher level of risk than absolutely necessary.

A Computed Tomography (CT) scan provides a wealth of important information on internal anatomy that is often unattainable with other types of imaging procedures. However, CT scans expose a patient to x-ray radiation, which may cause damage to the areas of the body that are exposed. Fortunately, the human body has a natural mechanism for repairing radiation damage. This mechanism is present to repair the body as a result of our continuous and unavoidable exposure to low levels of background radiation. One of the most common ways to express radiation dose is the sievert (Sv), which attempts to quantify the biological effects of radiation. In the United Kingdom, the average background radiation dose is approximately 2.5 milliSieverts (mSv) each year, with a large amount of variation depending on several factors, including higher doses (up to 9mSv per year) for individuals living in parts of Cornwall or Scotland due to local geology.

When the level of radiation exposure is low, such as is the case of performing a mammogram, a chest x-ray, or a low dose CT scan to detect cancer early, the benefits to the individual must once again outweigh the risks.
Men and women have an average lifetime risk of 40% of developing some kind of cancer.

In the case of a typical mammogram, the radiation dose is approximately 0.7 mSv for a single examination. A single 1.0 mSv dose of radiation is estimated to cause 1 cancer in 10,000 individuals. Thus a woman receiving 10 years of annual mammograms would then increase her lifetime risk of developing cancer from approximately 40.0% to 40.07%. Given that nearly 1 in 8 women will develop breast cancer, the benefits of regular mammography have generally been determined to outweigh the increased risk of causing cancer and thus women above the age of 40 are typically encouraged to regularly perform the procedure.

Annual low dose CT lung cancer screening should also be considered in the context of individual benefits and risks. The I-ELCAP and NELSON lung cancer screening trials utilize particularly low dose CT settings and achieve high resolution CT scans of the lungs with a dose of approximately 1.0 mSv. Similar to mammography, a person receiving 10 years of annual low dose CT lung cancer screening would increase their lifetime risk of developing lung cancer by 0.1 %.

On average one in 15 people will be diagnosed with lung cancer in their lifetime, with much higher odds for those with a higher number of risk factors. Although cancer screening is under constant scientific debate, over ten years of study on screening for early lung cancer has shown the potential to detect a significant percentage of lung cancers at an early, curable stage. For individuals with elevated lung cancer risk, such as those that have previously smoked or individuals with a family history of lung cancer, the potential benefits and risks of lung cancer detection with low dose CT are likely to outweigh any risks.

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