Expect 'Stage Shift' in Lung Cancer After Trial Results

Zosia Chustecka

July 06, 2011

July 6, 2011 (Amsterdam, the Netherlands) — Lung cancer experts heaped praise on the the National Lung Cancer Screening Trial (NLST), which has shown a reduction in mortality with early detection.

The results, published online June 29 in the New England Journal of Medicine and reported at the time by Medscape Medical News, show that screening with low-dose spiral computed tomography (CT) reduced mortality from lung cancer by 20%. CT screening was compared with chest x-rays, which have not shown any mortality reduction in previous trials.

Discussing the results at the opening press conference here at the 14th World Conference on Lung Cancer, experts praised this "enormous achievement."

Dr. John Field

"This is the most important publication in lung cancer in a decade," said John Field, MD, from the University of Liverpool Cancer Research Center in the United Kingdom, and chair of the International Association of Study on Lung Cancer (IASLC) CT Screening Task Force, which held a workshop prior to the conference.

Early diagnosis is more important for lung cancer than for any other cancer.

Lung cancer is often diagnosed at an advanced stage. When it reaches stage 4 and has metastasized, there is really no hope of curative therapy and all treatment is palliative, he explained. "So early diagnosis is more important for lung cancer than for any other cancer," he said.

On the basis of what transpired in the breast cancer field after mammography was found to be effective, "we can now expect to see a stage shift in lung cancer, with changes in management that hail a new era in lung cancer treatment," he said.

"We are on the crest of a wave of an enormous change in lung cancer," Dr. Field told journalists.

The NLST is the first randomized trial to show a significant reduction in mortality, but several others are ongoing. One of the largest is the Dutch–Belgian NELSON trial, expected to report final results in 2015. This has a slightly different design, in that it is comparing 1 CT scan with usual care, whereas the NSLT compared 3 years of annual CT scans with annual chest x-rays.

In addition, there are ongoing CT screening trials in Italy and Germany, and a trial has just been started in the United Kingdom. "We are hoping to bring all of those data together," he said, so there should be more answers over the next 3 to 4 years.

The details of exactly how lung cancer screening should be implemented and incorporated in public health initiatives still need to be worked out, and the IASLC CT Screening Task Force is working on guidelines.

Discussion is "Appropriate"

In the meantime, the IASLC has released a consensus statement, which states that it "is appropriate" for physicians to be discussing these results with individuals who are at high risk for lung cancer, and to discuss with such individuals screening with spiral CT. The statement stipulates that these individuals should be heavy smokers who are 55 to 74 years of age, like the participants in the NSLT.

Dr. Denise Aberle

Spiral CT is readily available globally, said Denise Aberle, MD, from the University of California in Los Angeles, but the implementation of CT screening for lung cancer needs to be carefully controlled to preserve the benefits and minimize the risks.

Dr. David Baldwin

For high-risk individuals, such as participants in the NSLT, there is a good benefit/risk ratio, but for people who are at low risk, the potential harm could outweigh any potential benefit, said David Baldwin, MD, from the Nottingham Lung Cancer Center in the United Kingdom.

"There is great concern that screening needs to be offered to the correct individuals," he said. In addition, the discussion needs to be detailed, so that people are informed of all the consequences of screening in a way that they understand, Dr. Baldwin noted.

One of the negative findings from the NSLT is the very high rate of false positives — 95% of the findings on both CT and chest x-rays turned out not to be lung cancer.

The clinical work-up of indeterminate findings — such as nodules that do not appear to be cancer but are too large and suspicious to dismiss — varies from country to country and from institution to institution, but it can include fine-needle aspiration biopsy, bronchial washings, and surgery.

These investigations can involve both physical and mental harm, explained Dr. Baldwin. "There is a delicate balance between benefits and risks," he added, and that balance changes in different individuals.

CT screening is not just about taking the picture.

CT screening is "not just about taking the picture; it is this whole process," noted James Mulshine, MD, a medical oncologist from Rush University Medical Center in Chicago, Illinois. "We need refinement of this going forward," he continued.

Dr. Mulshine noted that the ongoing NELSON trial, in which only 1 CT scan is taken, reported a much lower false-positive rate — around 15% — when an interim analysis was published in 2009.

Echoing the sentiment that the screening involves more than just the scan, Dr. Field said that the screening and the follow-up need to involve a multidisciplinary team, and should only be carried out at centers where such a team is in place. "There needs to be good radiology, good pathology, good surgery," he said.

"It takes a team to treat lung cancer, and it will take a team to screen and diagnose it," agreed Roy Herbst, MD, from the Yale Cancer Center in New Haven, Connecticut, which is one of the first centers in the United States to offer CT screening for lung cancer.

"We have made the decision to offer such screening," he said, and so have several other centers, including the University of Texas M.D. Anderson Cancer Center in Houston, he added.

Whether screening will be covered by medical insurance is "unclear" at present, Dr. Herbst said. But he suggested that it should be covered because it has been shown to be effective — the clinical trial did meet its primary end point. In fact, the trial was stopped a year earlier than planned because the significant reduction in mortality provided an answer to the study's main question, according to an IASLC statement.

Dr. Richard Gralla

"We do see effectiveness," said Richard Gralla, MD, from the Hofstra North Shore-Long Island Jewish School School of Medicine Health System in New York, and he predicted that future analyses will also show cost effectiveness.

"If we do also show cost effectiveness, then this is evidence-based medicine, and it behooves all insurance companies and health authorities to cover it worldwide," he said.

Linked to Smoking Cessation Efforts

Another point emphasized by all of the experts is that screening must be linked to counseling on smoking cessation. This must be in place so that a high-risk individual who has a normal scan does not think that it is okay to carry on smoking, said Dr. Gralla. "We must emphasize that this is not the case," he added.

Individuals who have a normal scan should be told what symptoms of lung cancer to look for, be reminded that they remain at high risk, and be "strongly counseled" to give up smoking, noted Dr. Baldwin.

"We must integrate smoking cessation" into the screening paradigm, agreed Dr. Field. While heavy smokers are the initial target population, the next major challenge is people who smoked heavily in the past but who have since stopped, he said.

Dr. Field is chair of the IASLC CT Screening Task Force; Dr. Baldwin and Dr. Mulshine are members of this group. Dr. Field reports being a consultant for Epigenomics Berlin. Dr. Baldwin reports serving on the speakers bureau for Pierre Fabre. Dr. Herbst reports serving on the advisory committee for Amgen, Biothera, Genetics Squared, Med Trust, N of One, SynDevRx, Targeted Molecular Diagnostics, and Diatech.