SAN DIEGO—If a surgeon can perform an R0 wedge resection of a non-small-cell lung cancer, the distance to the negative margin does not appear to make a difference in long-term outcome, researchers reported here at the Society of Thoracic Surgeons Annual Meeting.
After patients were followed for a mean of 31 months, locoregional recurrence occurred in 26.4 percent of the patients undergoing the wedge resection, said Giulio Maurizi, MD, a thoracic surgeon at S. Andrea Hospital Sapienza at the University of Rome.
But it didn't seem to matter how wide the cancer-free margins were.
He said that about 26.7 percent of the patients who had a cancer-free margin of one centimeter or less developed locoregional recurrence, compared with 27.5 percent of patients who had a margin of one to two centimeters and 25 percent of those with a margin of two or more centimeters.
Twenty patients—11 percent of the total—developed distant metastases—four who had less than a centimeter margin; 11 who had a margin of one to two centimeters, and five with a margin of more than two centimeters.
Maurizi said that even when logistic regression analyses were performed taking into consideration the health status of the patients, the researchers were unable to see any advantage in outcome that could be attributed to the width of the cancer-free margin.
“There is general agreement within the surgical community that lobectomy offers better chances for a cure than wedge or segment resection in Stage 1 non-small-cell lung cancer. However, sublobar resections are a viable option for the treatment of small stage I non-small-cell lung cancer when lobectomy is contraindicated,” Maurizi said in his oral presentation.
“In this analysis, the distance between the tumor and the parenchymal suture margin does not influence recurrence and the survival rate when R0-resection is achieved,” he said.
Ideal Remains Controversial
He said that the ideal cancer-free margin for a wedge resection in these patients with severe underlying comorbidities remains controversial—“prospective trials and larger investigations are required.”
His conclusions, however, were challenged by several audience members, who cited previous work indicating that margin was indeed meaningful in outcomes. The co-moderator of the session, Jules Lin, MD, Assistant Professor of Surgery at the University of Michigan, Ann Arbor, noted that studies conducted at Brigham & Women's Hospital found that the greater the margin difference, the better the outcome.
Other members of the audience sought explanation about the methodology of the study and the makeup of the tumors.
Maurizi acknowledged that his study's conclusions were limited by the retrospective nature of the work; by the relatively limited number of patients; and by the significant comorbidities of the patient population that contraindicated lobectomy and with that potential impact on long-term outcome.
However, he said that his findings were based on a “homogeneous sample of patients, undergoing the same operation, by the same technique, with a complete pathological staging. This is a very important aspect of our trial.”
He said that all the patients had solid tumors. Patients with so-called ground glass tumors were excluded from the study, he said in respionse to one queston.
Leah Backhus, MD, Assistant Professor of Surgery at the University of Washington in Seattle, said in an interview: “I don't think it makes a difference how big the margin is if you achieve an R0-resection. I don't obsess over how wide the margin is. What these researchers have found makes sense to me.
“I don't try for a close margin,” she explained. “I take as generous a margin as is reasonably feasible to do. Whatever that gives you, it gives you, and provided it is negative, you take it.”
She said controversy arises from what people write in papers and in textbooks, but “in practice I don't think the width of the negative margin is controversial at all. You would never go back and reoperate to get more margin, so if it is negative, that is what we aim to get. This study simply validates what is done in current practice patterns.”
In his retrospective analysis of these high-risk patients who were treated with wedge resection and lymph node dissection from 2003 to 2013, Maurizi and his colleagues identified 243 patients who had undergone the wedge resection, 182 of whom had achieved an R0 resection of the lung cancer.
At presentation, about 76 percent of the patients were diagnosed with Stage T1a NSCLC; 16.5 percent were diagnosed with T1b disease and about eight percent were diagnosed with T2a disease. About 61.5 percent of the patients were determined to have adenocarcinoma; 16.5 percent were diagnosed with squamous cell carcinoma; and the remaining 22 percent were diagnosed with other histologies.
The T1 tumors ranged in diameter from 3.1 to 3.4 centimeters.
Patients who had cancer-free margins by pathology following surgery were stratified into three groups, based on margin distance. Overall, the patients' mean age was 70.9 years and they had a 55.17 percent of predicted FEV1 (forced expiratory volume in 1 second), a measure of lung function.
A total of 30 patients had a wedge resection that had a cancer-free margin of less than one centimeter. Twenty were men; more than half of this group was smokers; 40 percent had cardiovascular disease; 20 percent were diabetic; and 30 percent had severe chronic obstructive pulmonary disease.
There were 80 patients in the group who underwent wedge resection and had cancer-free margins of one to two centimeters. About 73 percent of patients in this group were men; 60 percent were smokers; 76.5 percent had cardiovascular disease; 12.5 percent had diabetes; and 36.3 percent had severe chronic obstructive pulmonary disease.
The remaining 72 patients in the study had wedge resections in which the cancer-free margin was greater than two centimeters. About 71 percent of this group was men; 60 percent were smokers; 67 percent had documented cardiovascular disease; 15 percent were diabetic and 31 percent had chronic obstructive pulmonary disease.
Overall survival in the patients in the study was 75.5 percent at three years; 70.4 percent at five years, Maurizi reported. Overall disease-free survival was about 65 percent at three years and 52 percent at five years.
He noted that overall survival based on the size of the margin failed to achieve statistical significance, and neither was overall disease-free survival based on the size of the cancer-free margin.
The researchers also looked at the cancer-free margin size for the patients with the most favorable diagnosis—the T1a patients. Locoregional recurrence occurred among 25 percent of the patients with a margin or less than one centimeter; among 25.5 percent of patients with a margin of one to two centimeters and among 23.5 percent of patients with a margin more than two centimeters. The respective rates for distant recurrences were 12.5, 12.7, and 5.9 percent.
Two patients in the study died during the perioperative period—one from a heart attack and one due to pneumonia.
About 34 patients (about 19%) of the group undergoing the wedge resections had post-surgical complications, including 11 patients who developed air leaks and eight who developed atrial fibrillation.