The More the Nodes, the Better for Colon Cancer

HOUSTON, March 20 -- The more lymph nodes removed and evaluated during colon cancer resection, the better the outcome, reported investigators here.

When more than 20 lymph nodes are evaluated, there is a 14% increase in five-year survival, reported George Chang, M.D., of the M. D. Anderson Cancer Center, and colleagues, in the March 21 issue of the Journal of the National Cancer Institute.

"Currently just over one-third of colon cancer patients in the United States are getting an adequate lymph node evaluation," said Dr. Chang and colleagues, who conducted a systematic review.

Sixteen of 17 studies Dr. Chang and colleagues examined found that an increased number of lymph nodes evaluated was associated with improved survival of patients with stage II disease. Similarly, four of six studies looking at node-positive colon cancer (stage III) also found a link between nodes evaluated and survival.

"The number of lymph nodes recovered from a patient with colon cancer has been identified as a potentially important measure of the quality of cancer care by many organizations, including the American College of Surgeons, the American Society of Clinical Oncology, the National Comprehensive Cancer Network, the National Quality Forum, health insurance providers, and others," Dr. Chang and colleagues noted.

The authors acknowledged that because all of the studies they reviewed were observational and varied in quality and design, they could not establish whether there was a causal relationship between the number of lymph nodes evaluated and survival.

Also, judging the quality of care by the number of nodes excised and examined could be misleading, cautioned colorectal surgeon Rocco Ricciardi, M.D., of Tufts in Boston, and Nancy N. Baxter, M.D., Ph.D., of St Michael's Hospital at the University of Toronto, in an accompanying editorial.

"Before lymph node benchmarks are established as a quality measure, two important questions must be addressed," they wrote. "First, who or what is being evaluated when we report lymph node counts -- the surgeon, the pathologist, the hospital, the patient, or even the tumor? Because each component may have an influence on the overall lymph node harvest, it will be a major challenge to establish whose quality we are measuring."

"Second, on a more fundamental level," they continued "will quality improvement projects aimed at increasing reported lymph node number actually lead to improved patient outcomes? That lymph node number is associated with survival seems beyond dispute; however, no research has determined the mechanism underlying this association."

They added, "In fact, it is likely that the number of lymph nodes evaluated in a given patient reflects, at least in part, the underlying interaction between tumor and host, and this interaction itself may have important prognostic implications. The lymph node microenvironment has a primary function in immunologic surveillance, enabling immunologic responses of the host to the tumor."

The M.D. Anderson investigators scoured medical databases for studies published from the beginning of 1990 through June 30, 2006, that included data on survival as a function of the number of lymph nodes evaluated.

They identified a total of 17 studies, from nine countries, covering 61,371 patients. The studies included two secondary analyses of multicenter randomized trials of adjuvant chemotherapy for colon cancer, five population-based observational studies, and 10 single-institution retrospective cohort studies.

The studies varied widely both in their methodology and in the number of lymph nodes sampled in each, from a low of six to a high of 40. Nonetheless, the authors were able to determine that there were significant survival benefits for more lymph node dissections compared with fewer.

For example, they found that the nested cohort Intergroup 0089 trial from the U.S., a nested cohort study, there was a 14% higher absolute five-year overall survival for patients with stage II colon cancer who had more than 20 negative lymph nodes examined, compared with 10 or fewer.

In the same study, there was also a 12% higher absolute cancer-specific survival among patients with stage II disease who had more than 20 lymph nodes evaluated, compared with those in whom only 10 lymph nodes were evaluated. There was a non-significant trend toward improved disease-free survival in stage II patients in the trial.

Overall survival at eight years was 79% for those who had 20 negative lymph nodes examined, compared with 59% for those with fewer than 10 negative nodes evaluated. This translated into an absolute overall survival difference of 20% absolute (P