SAN FRANCISCO—The number of negative lymph nodes identified during surgical resection of stage III colorectal cancer predicts long-term survival independently of the number of positive nodes identified, new data show. Lead author Nancy N. Baxter, MD, PhD, a colon and rectal surgeon at St. Michael's Hospital, Toronto, presented the study results at the 2006 Gastrointestinal Cancers Symposium (abstract 219).
Studies of the association between total number of lymph nodes evaluated and survival in stage III colorectal cancer have yielded inconsistent results, Dr. Baxter said. "This is likely because total number of nodes is a factor, of course, of both number of positive nodes and number of negative nodes," she noted. "We know that a higher number of positive nodes is associated with a worse prognosis, where—as we think it's potentially possible that the number of negative nodes is associated with a better prognosis, so you have two competing factors that add up to the total number of nodes."
Dr. Baxter and her colleagues analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database from patients with invasive adenocarcinoma of the colon or rectum that was stage III based on AJCC staging criteria. All of the patients had undergone radical surgery, and none had received preoperative radiation therapy. The cancer had been diagnosed between 1988 and 1997, and follow-up was conducted through 2002. In analyses, patients were stratified into quartiles based on the number of negative lymph nodes identified (≤ 3, 4-7, 8-12, and ≥ 13).
The study included 24,289 patients with stage III disease; the substage was IIIA in 10%, IIIB in 58%, and IIIC in 32%. The mean age of the population was 68 years; researchers identified a median of seven negative nodes and two positive nodes. "The correlation between the total number of positive lymph nodes and the total number of negative lymph nodes was negligible-to-weak for our substages, ranging from -0.03 to -0.13," Dr. Baxter noted.Incidence of Death
During the mean 5.1-year follow-up, the incidence of death from colorectal cancer was 16%, 34%, and 47% in the stage IIIA, IIIB, and IIIC groups, respectively. Cancer-specific survival did not differ by quartile of number of negative lymph nodes among patients with stage IIIA disease, but increased significantly with quartile among patients with stage IIIB and IIIC disease.
Comparing patients in the highest quartile of negative lymph nodes (≥ 13) with those in the lowest (≤ 3), the 5-year cumulative survival was essentially the same in stage IIIA disease (88% vs 87%), but differed substantially in stage IIIB disease (73% vs 56%) and in stage IIIC disease (61% vs 39%).
In a multivariate model that included age, sex, race, tumor grade, tumor location, registry, and both positive and negative lymph node counts, patients in the highest quartile of number of negative lymph nodes were significantly less likely than their counterparts in the lowest quartile to die in the stage IIIB group (hazard ratio [HR] 0.54, P < .0001) and the stage IIIC group (HR 0.49, P < .0001).
