CHICAGO – The extent of lymph node involvement provides independent prognostic information in patients with early-stage T1 or T2 small intestinal neuroendocrine tumors, according to a study involving nearly 3,000 lymph node–positive individuals.
This metric, best expressed as the lymph node ratio, or the number of positive nodes divided by the total number of lymph nodes examined, is not included in current European and American Joint Committee on Cancer staging classification guidelines. But it should be, Dr. Michelle K. Kim said at the annual Digestive Disease Week.
"The lymph node ratio is a readily available marker of disease progression. It’s available as part of usual clinical care; it’s not something extra you have to ask for. It may help identify patients who may require more-aggressive therapy," according to Dr. Kim of Mount Sinai School of Medicine, New York.
Current staging guidelines merely make a binary distinction: lymph node–positive or –negative. But previous studies in colon, gastric, and pancreatic cancers indicate the lymph node ratio (LNR) further differentiates outcomes in node-positive patients. The same now appears to be true for small intestinal neuroendocrine tumors (SI-NETs), which are the most common of the gastroenteropancreatic neuroendocrine tumors. Indeed, the incidence of SI-NETs has tripled during the last 3 decades, she noted.
Dr. Kim presented an analysis of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, which included 2,984 patients with surgically resected lymph node–positive, metastasis-negative SI-NETs diagnosed in 1988-2010. Dr. Kim and coinvestigators classified patients into three LNR groups: 531 were LNR 1, defined as an LNR ratio of 0.2 or less; 1,525 patients were LNR 2, with a ratio of 0.21-0.5; and 928 were LNR 3, with a ratio greater than 0.5. Patients with T1 and T2 disease were overrepresented in the LNR 1 group.
The primary outcome in the study was disease-specific survival. The more-extensive the lymph node involvement in patients with T1 or T2 disease, the poorer their disease-specific survival. For example, LNR 1 patients with T1 or T2 SI-NETs were 1.6-fold more likely to experience disease-specific mortality during 10 years of follow-up than did a reference control group of node-negative T1/T2 patients, an elevation in risk that did not achieve statistical significance. However, the risk of disease-specific mortality was increased 2.29-fold in LNR 2 patients with T1/T2 disease and 4.52-fold in LNR 3 patients with T1/T2 SI-NETs, compared with node-negative controls, and those differences were significant.
In contrast, there was no difference in disease-specific survival according to LNR status in patients with more-advanced T3 or T4 disease.
This study was funded by Mount Sinai School of Medicine and the National Center for Advancing Translational Sciences. Dr. Kim reported having no financial conflicts.