Does CT Beat the Odds?

30 March 2008 (Last Updated March 30th, 2008 18:30)

Lung cancer is a deadly disease, but the benefits of lung cancer screening are hotly debated. Nic Paton sounds out the opposing views of Professor W Michael Alberts and Laurie Fenton Ambrose.

Currently, the only widespread screening available to patients at a high risk of developing lung cancer are chest X-rays. Unfortunately, such X-rays tend not to detect lung cancers at very early stages, when they are most curable.

So it is perhaps not surprising that research suggesting that advances in computed tomography (CT) scanning might be able to reduce mortality among some individuals has led to fierce debate among professionals and advocates in this field.

The key study in the debate was published in The New England Journal of Medicine in 2006. It argued that annual screening with spiral CT might reduce lung cancer death rates among individuals at high risk of developing the disease. While results from previous studies had indicated that annual screening with spiral CT tended to detect lung cancer at an early stage, the potential overall survival benefit for such patients following treatment had not been established until the 2006 study.

Then late in 2007 the journal Lung Cancer argued that low-dose CT screening substantially improved ten-year survival for lung cancer with the minimal use of invasive treatment procedures. Compared with the usual long-term survival rates among patients with lung cancer, the survival rates for these patients were "extremely encouraging", it concluded.

"CT scans are so sensitive now that they pick up everything. This is good, but it can also lead to false positives."

In this context it is little wonder that the move in September last year by the American College of Chest Physicians (ACCP) – which represents 16,600 members who provide clinical respiratory care, sleep medicine, critical care and cardiothoracic patient care in the US and elsewhere – to issue guidance recommending against the use of low-dose computed tomography (LDCT) for the general screening of lung cancer has proved controversial.

AMERICAN COLLEGE OF CHEST PHYSICIANS GUIDELINES

The guidelines provided in September 2007 include:

Screening

Because of the lack of supporting evidence, the guidelines recommend against the use of LDCT, chest radiographs or single or serial sputum cytologic evaluation for lung cancer screening in the general population, which includes smokers and others at high risk, except in the context of a well-designed clinical trial.

Bronchioalveolar carcinoma

For the first time, the American College of Chest Physicians (ACCP) has made recommendations on the diagnosis, prognosis and treatment of bronchioalveolar carcinoma (BAC), a type of lung cancer often seen in non-smokers or those with minimal smoking history. It suggests that, although staging, diagnosis and treatment are the same for BAC as for other histological subtypes of non-small cell lung cancer (NSCLC), additional treatment options exist that may prove as, if not more, effective for patients with BAC. These include sub-lobar resection and the use of epidermal growth factor receptor targeted agents.

Adjuvant chemotherapy

Previous ACCP recommendations did not support postoperative chemotherapy for either stage I or stage II NSCLC. The new guidelines now support the use of platinum-based adjuvant chemotherapy for patients with completely resected Stage II NSCLC who have good performance status. The change in the recommendation was prompted by new research showing that adjuvant therapy significantly reduced the risk of death in patients with Stage II NSCLC.

Solitary pulmonary nodules

The guidelines include recommendations on the management of solitary pulmonary nodules (SPN), rounded opacities commonly noted on chest radiographs or CT scans. The new recommendations outline a specific algorithm for the evaluation and management of SPNs and stress the value of risk factor assessment, the utility of imaging tests, the need to weigh the risks and benefits of different management strategies and the importance of obtaining patient preferences.

THE CASE AGAINST LDCT

Professor W Michael Alberts, supports the ACCP recommendations and rejects the use of LDCT. Professor Alberts is immediate past-president of the American College of Chest Physicians. He is professor of oncology and medicine in the department of interdisciplinary oncology at the University of South Florida College of Medicine in Tampa, and chief medical officer at the H Lee Moffitt Cancer Center and Research Institute. He is the editor of the ACCP's Evidence-Based Guidelines on the Diagnosis and
Management of Lung Cancer.

What's important to stress, argues Professor Alberts, is that September's guidance was not new, but a reiteration of existing guidance. Essentially the recent research has not yet altered the landscape around the use of CT scanning, and in particular low-dose CT scanning, to screen for lung cancer.

"We do not recommend that low-dose CT scanning is used to screen for lung cancer except in the context of a clinical trial," he says. "Our guidance is evidence based, and we review the literature. At the moment no mortality benefit, other than just a survival benefit, has been proven. Since there is no mortality benefit, and some real risks, we do not recommend it for the wider population. We have to make sure we are not doing more harm than good.

"Having said that, we hope that the studies currently going on, which are expected to report over the next year or so, will show a mortality benefit, in which case we would gladly change our recommendations."

While such screening could be costly, this is not, and should not be, the key issue, he says. The key issue is the risk involved. The risk is twofold: first there is the danger from repeated exposure to low-dosage radiation. Secondly, and more importantly, there is the risk of false positive conclusions.

"CTs are so sensitive now that they pick up everything," he explains. "This is good, but it can also lead to false positives. Whatever you identify, and whether or not it turns out to be a benign nodule or not, you are obliged to continue to observe it, which increases the radiation risk. And it may even be necessary to test further using surgery.

"There is also the issue of the psychological risk to the patient. It may be nothing, it probably is nothing, but for the next year or two, the patient is going to be pretty stressed psychologically.

"If, however, lung cancer screening is shown to provide a mortality benefit," he adds, "then we would probably make a recommendation to carry out screening. If it was proved that there was a sizeable mortality benefit, screening would probably be in the same category as smoking cessation."

What you might be looking at in those circumstances is probably not so much wholesale screening of certain sections of the population as the screening of the sections or sub-sections considered most at risk, such as, say, heavy smokers, he says.

"If it is shown to provide a mortality benefit and not just a survival benefit then we would definitely reassess our guidelines."

THE CASE FOR LDCT

Laurie Fenton Ambrose of the Lung Cancer Alliance advocates the selective use of LDCT. Fenton Ambrose is president and chief executive of the Lung Cancer Alliance and oversees the creation and implementation of its public policy agenda and national grassroots network. She joined the alliance after serving as chief of staff for the Secretary of State for the Department of Commerce and has served as chief of staff for various other senators and representatives.

Fenton Ambrose argues that The New England Journal of Medicine research, as well as other findings, have changed nothing. She believes the ACCP is completely missing the point and doing patients, particularly patients at high risk, a disservice.

"The ACCP has made a recommendation that is not a recommendation at all," she says. "The profile of this disease is, sadly, so poor because there is so much stigma and there are so few survivors. It is like Aids or HIV 25 years ago. There is a similar stigma and a perception that it is all down to behavioural choice.

"Because of this, we do not have a lot of research, and there are few treatment options, unlike in breast cancer. Some 70% of diagnoses are late and there is still very little chance of surviving," she says.

"So if we can improve this situation through earlier intervention, that gives us an additional weapon. Given that the vast majority of people are diagnosed at a late stage, it is so exciting that there is now robust data that shows the benefits of CT in detecting lung cancer early."

But Fenton Ambrose concedes it is not the time to rush in and put in place some vast and hugely expensive national screening programme.

"The issue is not so much about CT finding lung cancer; it is really about CT finding suspicious nodules or calcification. Screening is not about the procedure but about the processing and managing of what you find," she says.

"We do not advocate a population-based strategy. We do not have the public health infrastructure for that. Our position is that for individuals who are at high risk of lung cancer – those with a history of smoking, for example, or a family history of the disease, or those who have been in an environment where they might have been exposed to certain particulates – the recommendation should be that they talk to their doctor about the risks and benefits of CT and then determine a course of action that is appropriate."

"There is now robust data that shows the benefits of CT in detecting lung cancer early."

Fenton Ambrose's response to the argument that there is as yet no evidence to recommend a shift of this nature is scathing. Randomised trials being carried out by the National Cancer Institute are some five years from concluding, she argues, and five years waiting doing nothing is simply not the answer.

"We really do need to push this rather than wait for the results before doing anything," she says. "There has never been a completely randomised trial for colonoscopy, while there have been eight for mammography and they have not completely resolved anything.

"The Lung Cancer Alliance would like the US Preventative Services Taskforce, which systematically reviews the evidence of effectiveness and develops recommendations for clinical preventive services, to say, in the light of the robust data in The New England Journal of Medicine, that it should be recommended that patients at high risk talk to their doctor about CT screening. The practical reality is that it is already happening. People are already having these conversations."

This may even be a moment for the US Congress to step in, she argues, as it did over mammography with the Mammography Quality Standards Act of 1992, which regulated the quality of care in mammography. "We would argue that Congress needs to be looking at this," she says.