"It is frustrating that the high percentage of stage I cases is not given sufficient recognition in terms of the number of lives that could be saved, because people are dying everyday."

Claudia I. Henschke, Ph.D., M.D.

Lung Cancer Revolution Imminent, Researcher Says

Dr. Henschke, along with colleagues from the International Early Lung Cancer Action Program (I-ELCAP), recently released a study suggesting that early screening may be useful in detecting lung cancers that are still curable. “Why should I take a whole lobe of the lung for something that is 5 or 6 mm?”

Dr. Henschke, of New York Presbyterian Hospital–Weill Cornell Medical Center, and colleagues published their article, “Computed Tomographic Screening for Lung Cancer: The Relationship of Disease Stage to Tumor Size,” in the February 13 issue of the Archives of Internal Medicine. It is well known, Dr. Henschke said, that lung cancers without evidence of lymph node metastases are more curable, with the curability rate being higher with smaller sizes.

The team noted that tumor size has, in the past, been identified as a prognostic indicator for stage I lung cancer as it was used to divide stage I into stages IA and IB. Their study, the authors wrote, provides direct evidence of a stage-size relationship in screening cases.

“The smaller they are, the more likely it is that they’re early and the more likely they can be cured,” added Dr. Henschke.

Screened Population Versus Registry Data

Lung cancer remains a leading cause of cancer death worldwide. In the U.S., it causes more deaths than breast, prostate, cervical and colon cancers combined. In spite of recent advances in surgical techniques, as well as in chemotherapy and radiation therapy, the overall survival rate has not improved appreciably in the past 40 years. The overall 5-year survival rate in the U.S. is only 14 percent and worldwide it is even lower.

In the Archives of Internal Medicine, Dr. Henschke and colleagues reported studying 28,689 asymptomatic men and women who underwent baseline CT screening, with 22,991 receiving repeat screening. The median age of enrollees was 61 and men made up 58 percent of the study participants. The median pack-years of smoking was 30.

A total of 464 lung cancer cases were diagnosed, 376 on initial screening and 88 on repeat screening. Grouping the 436 non-small cell carcinoma cases according to tumor diameter, the team found that 91 percent of tumors 15 mm or less had no metastases. Eighty-three percent of tumors 16 to 25 mm had no metastases, while 68 percent of tumors 26 to 35 mm had no metastases. Of tumors 36 mm or greater, 55 percent had no metastases.

 “The percentages of N0 M0 (no metastases) cases in screen-diagnosed lung cancers are much higher than previously reported in the Surveillance, Epidemiology and End Results (SEER) registry,” the authors wrote. “These results provide direct evidence of a stage-size relationship in a screened population.”

Debate Continues Over Benefit of Early Screening

Dr. Henschke said the results justify the benefit of early screening among populations at risk for developing lung cancer. Early stage I lung cancer has a curability rate of almost 70 percent, she explained, with some studies reporting much higher rates for smaller cancers. However, most cancers are not identified until the disease has progressed and symptoms become more pronounced. Lung cancer has no symptoms in its early stages, she added, which is another argument for the necessity of early screening. A person’s risk, she said, depends on how much he or she smoked, the person’s age and, if the person has quit, how long it has been.

Stephen J. Swensen, M.D., professor of radiology at the Mayo Clinic in Rochester, Minn., disagreed that the study conclusions constitute a call for early screening. The results are interesting, he said, but they won’t change radiologists’ day-to-day practices. “There’s no clear evidence that screening will save lives when you look at all populations with lung cancer,” he said.

The study is another small step in the accumulation of data and opinion regarding the utility and feasibility of lung cancer screening, said Eric J. Stern, M.D., professor of radiology and medicine at the University of Washington Harborview Medical Center in Seattle.

"At this time, I do not think there will be a great immediate clinical impact, as the screening trials are still under way,” said Dr. Stern, a chest radiologist.
“This is not to say the conclusions of the study might not have an impact in the future, as they could lead to continued refinement of the international system for staging lung cancer classification.

Dr. Henschke said she anticipates just such a stage shift, pointing again to recent changes in the staging of breast cancer as an example. However, because staging recommendations are just being considered by the International Association for the Study of Lung Cancer (IASLC) Staging Committee, changes could be three to four years away, she said.

“It is frustrating that the high percentage of stage I cases is not given sufficient recognition in terms of the number of lives that could be saved, because people are dying everyday,” she said.

Other Studies Continue

Dr. Swensen added that while “interesting and worthwhile” lung cancer studies are being conducted, “all will be overshadowed” when results are released from the National Lung Screening Trial (NLST), for which he is a principal investigator at Mayo. The NLST, sponsored by the National Cancer Institute (NCI), is a longitudinal randomized trial of subjects at high risk of developing lung cancer. Results are expected as soon as 2008.

“No one knows right now if we’re doing more harm than good by performing screenings,” Dr. Swensen said.

Dr. Henschke disagreed. She said that by following requisite screening and workup guidelines, radiologists can do more good than harm with early screening of high risk populations. As for NLST, she said a key drawback is that results will not be reported for several years.

“We report semi-annually, and we’re already reporting that if the cancer is found early and it’s small you have a high rate of cure—90 percent or better,” she said.

The effect of early screening will be very slow to show up in national survival rates, Dr. Henschke added, “A majority of people still are not getting screened because they have to pay for it.”

Dr. Henschke said she and her colleagues will publish in the next year a 10-year follow-up of cases in I-ELCAP. Other upcoming studies will look at combination lung/heart scans and the “rational recommendations” for early screening of people who never have smoked, she said. Trials of the treatment of lung cancer with radiofrequency ablation (RFA) and radiosurgery are also planned.

I-ELCAP is an international collaborative group created by a group of lung cancer experts. Screening sites for collaborative I-ELCAP projects are located worldwide.

To read the abstract for “Computed Tomographic Screening for Lung Cancer: The Relationship of Disease Stage to Tumor Size,” go to: archinte.ama-assn.org/cgi/content/abstract/166/3/321.

A small adenocarcinoma presenting as a solid nodule. Just behind the descending thoracic aorta, it would be obscured on the chest x-ray. The radiologic-pathologic correlation is good as it shows the tumor abutting the pleura and the highpowered view shows that it is an denocarcinoma.

Images courtesy of Claudia I. Henschke, Ph.D., M.D.