Ratio of metastatic to examined lymph nodes is a powerful predictor of overall survival in rectal cancer

Reviewer: James M. Metz, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 3, 2007

Presenter: M. O. Meyers
Presenter's Affiliation: Duke University Medical Center
Type of Session: Scientific

Background

It is well known that lymph node metastasis is associated with a worse outcome in rectal cancer. It has generally been accepted that 12 lymph nodes are needed for proper nodal staging. However, only 37% of patients in the SEER database with colon cancer had 12 lymph nodes evaluated. The Intergroup 0114 trial for rectal cancer had 52% with less then 10 lymph nodes evaluated. Because many patients are not having the recommended number of lymph nodes evaluated, this study was designed to determine if the ratio of positive lymph nodes to total examined lymph nodes is of prognostic significance.

Materials and Methods

Data from Intergroup 0114 were evaluated which was a postoperative adjuvant trial with radiation and chemotherapy in locally advanced rectal cancer
Because the overall survival was the same in each group, the overall study populations were combined for this analysis.
The lymph node ratio was defined as the number of lymph nodes positive divided by the number of lymph nodes examined
This study defined 4 groups based on this ratio: < 25% positive, 26-50% positive, 51-75% positive, and >75% positive

Results

Of the 1648 patients, 1135 were node positive (N1=643 and N2=392)
The median number of lymph nodes evaluated was 9
The lymph node ratio was predictive of overall survival with rates of 71%, 56%, 50%, and 43% when analyzed by the above quartiles respectively (p<0.0001).
The lymph node ratio was the strongest predictor of overall survival when compared with the number of lymph nodes examined, number of positive lymph nodes, number of negative lymph nodes, and AJCC nodal stage.

Author's Conclusions

Lymph node ratio predicts overall survival in patients with resected rectal cancer
This remains important even in patients with a small number of lymph nodes evaluated
Lymph node ratio is a stronger predictor of overall survival then other classic lymph node prognostic factors
Lymph node ratio may be helpful in stratification of node positive patients in future clinical trials.
This does not eliminate the need for adequate lymph node evaluation

Clinical/Scientific Implications

This study quantitates what most physicians already do when evaluating a pathology report for rectal cancer in the postoperative setting. It is consistent with what is expected that the overall tumor burden predicts outcome in this disease. Because many patients do not have adequate lymph nodes examined, this study helps to better define the risk of nodal disease based on the number of lymph nodes removed. However, most patients with locally advanced rectal cancer are now treated with neoadjuvant chemotherapy and radiation therapy and this model is not predictive of that group of patients. It is also unclear what is an adequate number of lymph nodes evaluated after neoadjuvant treatment because it is much harder to locate the nodes in the specimen after these therapies.