Lung cancer overdiagnosis may be overinflated

Volume-doubling time (VDT) estimates could help distinguish aggressive from nonaggressive screen-detected lung cancers, according to a study published Dec. 4 in the Annals of Internal Medicine. Researchers who applied VDT estimates to a high-risk screening population reported that 75 percent of CT-detected cancers were aggressive. However, they noted 25 percent of incident cancers were slow-growing, and many of these may have been overdiagnosed.

As providers deploy CT to screen high-risk patients for lung cancer, overdiagnosis of cancers that will never become symptomatic has emerged as a concern. Some critics of screening charge that it primarily detects indolent early cancers, and that treatment of such cancers may not reduce mortality.

Researchers acknowledged the double-edge sword of screening. “Whatever the size of the overdiagnosis problem, it may be counterbalanced by reduced mortality in screened patients,” wrote Giulia Veronesi, MD, of the European Institute of Oncology and School of Medicine at University of Milan, and colleagues. “Nonetheless, elucidating the characteristics and behavior of overdiagnosed cancer to help reduce overtreatment, patient stress and the costs of screening is important.”

Veronesi and colleagues sought to assess VDT for screening-detected lung cancer as an indicator for overdiagnosis. Between October 2004 and October 2005, the researchers enrolled 5,203 asymptomatic volunteers aged 50 years or older who were current or former heavy smokers to undergo annual screening CT exams for five years.

During the five-year study, 175 cases of primary lung cancer were diagnosed; 55 cases were prevalent and 120 cases were incident during subsequent screening.

The researchers used advanced visualization software to calculate lesion VDT and categorize nodules as fast-growing (less than 400-day VDT), slow-growing (VDT between 400 and 599 days) and indolent (VDT of 600 days or more).

Of the 120 cases of incident cancer, 101 were progressive from year to year, and 70 of these were fast-growing. The remaining 19 cases of incident disease were new and fast-growing cancers.

Median VDT was 52 days in the 19 cases of new cancer, 223 days in fast-growing cancer and 545 days in slow-growing or indolent cancer.

Lung cancer-specific mortality was 9.2 percent in new cancer compared with 0.9 percent in slow-growing or indolent cancer. Thus, “VDT seems to be a plausible indicator of cancer aggressivity in cases of incident cancer,” wrote Veronesi et al.

The researchers observed that most cases of lung cancer were fast-growing; approximately 75 percent of cases had a VDT of less than 400 days. These findings suggest that a reasonable threshold to separate aggressive from nonaggressive lesions is a VDT of 200 days, according to the researchers.

“Another important finding of our study was that early diagnosis and early treatment, even of fast-growing cancer resulted in good long-term survival for our patients, most of whom had stage I disease at diagnosis,” wrote Veronesi. However, the researchers cautioned that these results should be balanced against the number of patients who underwent invasive procedures for benign disease. In this study, 29 patients had invasive procedures for what turned out to be benign disease.

They noted that use of recently identified circulating molecular markers for lung cancers may help reduce the number of patients who undergo unnecessary invasive procedures.

The researchers also suggested that standard resection may be overtreatment for slow-growing disease, and noted that several studies are assessing long-term outcomes of limited resection with lobectomy and lymph node dissection for stage IA cancer with a diameter of 2 cm or less.

Veronesi and colleagues concluded by emphasizing the need for further studies to assess whether VDT can help reduce overdiagnosis in lung cancer screening programs.