Kemp Kernstine, MD, PhD

The study’s invited discussant Kemp Kernstine, MD, PhD, the Robert Tucker Hayes Foundation Distinguished Chair in Cardiothoracic Surgery at The University of Texas Southwestern Medical Center, Dallas, welcomed the findings, but expressed some concerns about the study. To begin, of a database of 94,708 lung cancer diagnoses, only 14,712 patients (15.5%) met the criteria for analysis, having complete information on R status and survival and having not received neoadjuvant chemotherapy.

“Shouldn’t this number be 100%?” Dr. -Kernstine questioned. “Statistically, that’s a concern. It implies some serious database problems, and potential bias exists. We need to evaluate how we might improve participation.”

In addition, the patients were diagnosed and treated between 1999 and 2010. Since that time, advances have been made in diagnosis, staging, surgical management, and surveillance, he pointed out. Other biases were also likely present, including an underrepresentation by continent; most patients were from Europe and Asia.

Nevertheless, the analysis was based on a cohort that was 10 times larger than previous study cohorts, and this “herculean effort” was multinational, with accurate collection of data, acknowledged Dr. Kernstine.

Survival Implications

The investigators clearly addressed an important issue—one that has implications for patient survival, he continued. For instance, almost 60% of stage IIIA patients will recur within 5 years, and even 10% of stage IA patients remain at risk after resection. “It would be helpful to determine factors that might help us identify patients who should be treated with adjuvant chemotherapy,” Dr. Kernstine added.

The analysis confirmed that patients with R2 status have worse survival than those with R1 and R0, and it confirmed that R(un) status is “a problem,” he noted. “Half the [International Association for the Study of Lung Cancer] series had an uncertain complete resection, and in this group, the survival is poorer—though it’s better than with R1 and R2.” The study also confirmed that in node-positive patients, R(un) status confers worse survival, although there were too few node-negative patients to draw conclusions, he continued.

The authors defined the descriptors of R(un) status to be inadequate lymph node assessment, positivity of the highest node, extracapsular invasion, N2 or bronchial margin showing carcinoma in situ, and positive pleural lavage. It is likely there are other relevant variables yet to be identified, he added, suggesting, “We still need to identify other markers demonstrating incomplete resection.” ■

DISCLOSURE: Dr. Kernstine reported no conflicts of interest.