CT lung ca screening: Is the controversy overblown?

Spiral computed tomography (CT), a highly sensitive technology that finds early lung cancers, has sparked both renewed interest and controversy in lung cancer screening.

According to the American College of Chest Physicians (ACCP) guidelines (Chest 132:1S-19S, 2007), CT screening has not been shown to reduce mortality in high-risk populations and may do more harm than good. However, the new ACCP guidelines, which recommend that screening be offered only in clinical trials, haven't quelled the ardent debate.

Some screening proponents even urge patients to disregard the ACCP guidelines, contending that CT screening should be a personal choice after conferring with a physician. Moreover, the Lung Cancer Alliance, the disease's only national advocacy group, publicly derided the ACCP guideline for flatly opposing CT screening for those individuals at high-risk for lung cancer.

W. Michael Alberts, MD, chair of the ACCP lung cancer guidelines, told Oncology NEWS International, "There have been no studies that have shown a mortality benefit from spiral CT screening. Given the potential risks involved, we couldn't recommend this procedure at this point."

The ACCP guidelines constitute an endorsement of an ongoing randomized NCI-funded study, the National Lung Screening Trial (NLST). "Our guidelines are evidence-based, and if we see evidence of a mortality benefit from the NLST, then our recommendations would potentially change," Dr. Alberts said.

I-ELCAP study

Proponents of CT screening generally argue that the controversy has been resolved, pointing to the International Early Lung Cancer Action Program (I-ELCAP), a large collaborative study led by Claudia I. Henschke, MD, PhD, of Weill Medical College of Cornell University.

I-ELCAP investigators concluded that annual spiral CT can detect clinical stage I lung cancer in a high proportion of persons when it is curable by surgery (N Engl J Med 355:1763-1771, 2006). Among patients diagnosed at baseline CT scan with stage I cancer and who received treatment, 92% were alive at 10 years.

According to Dr. Alberts, the I-ELCAP study showed a survival benefit, which is different from a mortality benefit. Survival data can be affected by three early detection biases: lead-time bias, length bias, and overdiagnosis.

"CT screening may have increased the rate of detection in the I-ELCAP study, but because of the indolent nature of the cancers it found, there may be no significant mortality benefit," Dr. Alberts said.

Dr. Henschke and her colleagues have countered that long follow-up is needed to show a mortality benefit for CT screening, and she fears the NLST's planned 3 to 6 years of follow-up after three rounds of screening will not be sufficient to show such a benefit.

Bach paper supports ACCP

A study published in JAMA (297:953-961, 2007) that analyzed three single-arm CT screening trials found no evidence that scanning reduced lung cancer deaths. Lead author Peter B. Bach, MD, MAPP, said in an interview, "Even though we had excellent cancer-specific survival, similar to I-ELCAP, survival of a few individuals does not equate to an overall benefit."

Dr. Bach said that although CT screening's high resolution may be able to intercept very small nodules, it also finds more naturally occurring benign lesions that pose little threat. He cautioned that at the guideline level, there must be solid evidence of mortality benefit that outweighs the potential for harms associated with unnecessary biopsies and invasive treatments for low-risk cancers.

His study found a 10-fold increase in lung cancer surgeries resulting from CT screening. "If the majority of excess early cancers are unlikely to progress to clinically significant disease, then the surgeries used to remove them may not justify the resulting morbidities," Dr. Bach said.

He emphasized that the notion that CT screening is embroiled in controversy is overblown. "There might be a single vocal advocacy group shooting out press releases, but there is no professional organization that recommends CT screening for lung cancer," he said.

Experts challenge ACCP

Even in the absence of guideline recommendations, many experts believe that individuals at high-risk should have the option of participating in ongoing protocol-driven programs for early detection.

James L. Mulshine, MD, an internationally recognized lung cancer expert who has served as head of the Center for Cancer Research at the National Cancer Institute, spoke to ONI about the controversy. "We have strong evidence that CT screening can detect more frequent stage I lung cancers, and it is essential that early trials show these trends if we are ultimately going to find a mortality reduction," he said.

Dr. Mulshine explained that over the past 5 to 8 years, a body of credible research has shown that if managed by skilled doctors in centers of excellence, morbidity related to screened cancers can be very modest.

While acknowledging that CT screening is undergoing flux with new data emerging, Dr. Mulshine stressed that outcomes are significantly better in patients diagnosed at earlier, resectable stages. "If curative resections are made possible, mortality rates from lung cancer would decrease," he said.

Lung cancer bias?

Advocates contend that a societal bias against lung cancer patients has left the disease overlooked and underfunded. They point out that scientific debate still swirls around other screening methods, such as mammography and PSA testing, but these tools are still routinely employed.

"It's interesting to contrast the circumstances in lung and prostate cancer screening," Dr. Mulshine said. "The US Preventive Services Task Force concluded that lung cancer and prostate cancer screening are essentially in the same category. In both diseases, the screening evidence for benefit and harm is inconclusive."

Dr. Mulshine said that Medicare reimburses for prostate cancer screening, and with such support PSA tesing has gained broad implementation in advance of validated mortality reduction, especially from randomized, controlled trials.

"But in lung cancer we have this firestorm," Dr. Mulshine said. "Prostate cancer has a 99% 5-year survival, compared with 15% in lung cancer. So, theoretically, the potential benefit for lung cancer screening may be far greater than in prostate cancer."

He added that the ACCP guidelines overlooked the deliberations of the US Preventive Services Task Force, which suggested that on the strength of case-controlled trials from Japan, and other evidence, the Task Force could not determine the balance between the benefits and harms of lung cancer screening. Therefore, according to the American Cancer Society, among others, it is appropriate for individuals at high-risk for lung cancer to make an educated informed decision with their physician about spiral CT screening.

"The ACCP is at odds with some respected sources of reliable screening information," Dr. Mulshine said.

Early detection, more research

If the maxim "early detection leads to better outcomes" has reduced the mortality rate in other cancers, why not lung cancer?

Dr. Mulshine said we need to embrace a sensibility in public health, which includes smoking cessation programs and harnessing the power of CT screening in a carefully validated approach.

"We're working to improve screening services in breast and colon cancer. Shouldn't we have the same dedication to lung cancer screening?" he asked.