Surgery Options Weighed in Early NSCLC

BY JEFF EVANS
Elsevier Global Medical News

Segmentectomy could be the procedure of choice for preserving lung function in patients with peripheral stage IA non-small cell lung cancer if indeed it can provide the same rate of disease-free survival as lobectomy.

A randomized trial currently underway should help to address some of the surgical community's concerns about the size and conduct of the previous randomized trial that made lobectomy the surgical standard of care for most patients with early, node-negative, non-small cell lung cancer (NSCLC), said Dr. Nasser K. Altorki, FCCP, one of the study chairs for the current trial.

The earlier trial of 247 patients by the Lung Cancer Study Group (LCSG) showed that lobectomy resulted in a significantly lower rate of loco-regional recurrence than did segmentectomy or wedge resection. (Locoregional recurrence was a secondary end point.) There also were no significant differences in perioperative morbidity or mortality or late postoperative lung function between the two procedures (Ann. Thorac. Surg. 1995;60:615-22).

Patients in the LCSG trial had tumors with a median size of nearly 3 cm, but in the intervening time since they enrolled, improvements in cancer detection with CT scanning have made it possible to detect tumors smaller than 2 cm.

Furthermore, nearly one-third of the patients who underwent sublobar resection in that trial received a wedge resection, even though it is considered to be a "lesser procedure" than segmentectomy, Dr. Broadus Z. Atkins of the division of thoracic surgery at the Durham (N.C.) Veterans Affairs Medical Center said in an interview.

Subsequent retrospective studies of patients who underwent sublobar resection with segmentectomy or wedge resection for peripheral stage I NSCLC of 2 cm or less in size found survival rates similar to those of patients who underwent lobectomy. Further support for a 2-cm cutoff for performing segmentectomy came from the International Association for the Study of Lung Cancer's decision to subdivide stage T1 NSCLC into T1A (2 cm or less) and T1B (2-3 cm), based on survival differences seen in an analysis of thousands of patients with stage I NSCLC, Dr. Altorki said in an interview.

A switch from lobectomy to lung-sparing surgical techniques such as segmentectomy or wedge resection for tumors less than 2 cm in size on CT is analogous to the evolution of the use of lumpectomy vs. mastectomy for small breast cancers detected by mammography, he said.

"As diagnostic modalities and technologies improve, you find tumors at earlier and earlier stages. Therefore, the treatment options have to keep up with these improvements in technology. You cannot continue to offer the same treatments that were predicated on larger tumors that are more advanced," said Dr. Altorki, professor of cardiothoracic surgery and director of the division of thoracic surgery at New York-Presbyterian Hospital, New York.

To determine if disease-free survival after sublobar resection (segmentectomy or wedge resection) is noninferior to lobectomy, Dr. Altorki and his colleagues are currently enrolling patients at about 120 centers in the United States, Canada, and Australia in a phase III trial (labeled as Cancer and Leukemia Group B 140503). They hope to randomize more than 700 patients with pathologically confirmed, stage IA NSCLC 2 cm or less in size and negative lymph nodes in the hilum and mediastinum to either procedure. They plan to use either open surgery or video-assisted thoracoscopy. Patients will have follow-up visits every 3 months for the first year, then every 6 months in the second year, and annually for up to 5 years. Final outcomes for the trial's primary end point will not be available until 2012.

If the CALGB 140503 trial demonstrates equivalent survival between the two procedures, segmentectomy should preserve lung function in patients who intrinsically have less lung function because of their age and status as current or former smokers. Patients who develop a second primary tumor after being cured of the first one will have more treatment options for the second tumor, he said.

Dr. Altorki noted that a similar, but larger, randomized trial is underway in Japan.

Dr. Atkins said that he and his colleagues at the VA have been performing segmentectomy most often in patients who have undergone a previous lung resection or in those known to have poor lung function without a previous resection. The CALGB 140503 trial should help to determine if segmentectomy can be extended to patients who are otherwise "healthy" who would have previously undergone lobectomy, he said.

The trial is sponsored by the Cancer and Leukemia Group B, the National Cancer Institute, the Radiation Therapy Oncology Group, the American College of Surgeons Oncology Group, and the Southwest Oncology Group. For more information about the CALGB 140503 trial, visit clinicaltrials.gov/ct2/show/NCT00499330.

Dr. Richard Fischel, FCCP, comments: This article accurately and succinctly describes a trial that is critical to the future treatment of lung cancer. We often quote the old data as a reason to resect a quart of lung tissue to remove a pea-sized tumor. The morbidity for older and sicker patients should not be underestimated.