Int J Colorectal Dis. 2013 Oct;28(10):1377-84. doi: 10.1007/s00384-013-1707-8.

An appraisal of lymph node ratio in colon and rectal cancer: not one size fits all.

Medani M, Kelly N, Samaha G, Duff G, Healy V, Mulcahy E, Condon E, Waldron D, Saunders J, Coffey JC.

Department of General and Colorectal Surgery, University Hospital Limerick, Limerick, Ireland.

 

Abstract

BACKGROUND: Lymph node ratio (LNR) is increasingly accepted as a useful prognostic indicator in colorectal cancer. However, variations in methodology, statistical stringency and cohort composition has led to inconsistency in respect of the optimally prognostic LNR.

OBJECTIVE: The aim was to apply a robust regression-based analysis to generate and appraise LNRs optimally prognostic for colon and rectal cancer, both separately and in combination.

METHODS: LNR was established for all patients undergoing either a colonic (n = 379) or rectal (n = 160) cancer resection with curative intent. The optimal LNR associated with disease-free and overall survival were established using a classification and regression tree technique. This process was repeated separately for patients who underwent either colonic or rectal resection and for the combined cohort. Survival associated with differing LNR was estimated using the Kaplan-Meier method and compared using a log-rank test. Relationships between LNR, disease-free survival (DFS) and overall survival (OS) were further characterised using Cox regression analysis. All statistical analyses were conducted in the R programming environment, with statistical significance was taken at a level of p < 0.05.

RESULTS: Optimal LNRs differed between each cohort, when either overall or disease-free survival was considered. LNRs generated from combined cohorts also differed from those generated by individual cohorts. In relation to DFS, LNR values were obtained and included 0.18 for the colon cancer cohort and 0.19 for the rectal and combined colorectal cancer cohorts. In relation to OS, multiple LNR values were obtained for colon and combined cohorts; however, an optimal LNR was not evident in the rectal cancer cohort. Survival patterns according to LNR closely resembled those associated with standard nodal staging.

CONCLUSION: Application of a data-driven approach based on recursive partitioning generates differing lymph node ratios for colon, rectal and combined colorectal cohorts. In each cohort, LNR was similarly prognostic to standard nodal staging in respect to overall and disease-free survival. Overall survival was associated with a multiplicity of LNR values, whilst disease-free survival was associated with a single LNR only. The paper demonstrates the merits of utilising a data-driven approach to determining lymph node ratios from specific patient cohorts. Utilising such an approach enabled the generation of those LNRs that were most associated with particular survival trends in relation to overall and disease-free survival. These differed markedly for colon cancer, rectal cancer and combined cohorts. In general, the survival patterns associated with LNRs generated were similar to those observed with standard nodal staging.

PMID: 23715847

 

SUPPLEMENT:

Lymph nodes draining the colon and rectum are located within the mesocolon and mesorectum, respectively. These lymph nodes are located within the associated region of the mesenteric organ between the two layers of surface and deep mesothelium (figure 1). Our group has very recently extensively characterized the macroscopic and microscopic structure of the mesocolon, which provided an opportunity to determine the structure of the colonic and rectal lymphatic networks1.

The total number of harvested nodes has been used as a surrogate indicator of the quality of colorectal cancer resections, and the number of tumour-infiltrated (positive) lymph nodes is used as a prognostic indicator. Nodal staging within the accepted tumour-nodes-metastasis (TNM) staging for colorectal cancer is stratified according to the absolute number of positive nodes examined. This is subject to numerous limitations, not restricted to the technical aspects of the quality of the resection and pathological examination. For example, utilization of neoadjuvant chemoradiotherapy in rectal cancer reduces overall nodal harvest without impact on outcome. Moreover, colonic and rectal cancers are increasingly being recognised as separate entities, requiring different approaches to treatment, and possibly prognosis.

Lymph node ratio (LNR) refers to the ratio of positive lymph nodes in relation to the total number of harvested nodes. The prognostic value of LNR has been well-established for several solid organ malignancies, and its potential in colorectal cancer has recently been recognized. However, differences in methodological stringency and variations in examined cohorts have yielded differing results from separate groups. To this end, we used a data-driven approach based on robust statistical analyses to generate and appraise LNRs that are optimally prognostic – for colon cancer, rectal cancer, and the combined colorectal cohort.

Using regression-analysis, we obtained optimal LNRs for each of the cohorts; as we anticipated, results were different for each cohort. We then evaluated the prognostic significance of these values in relation to 5-year overall survival (OS), and disease-free survival (DFS) in each group. We obtained prognostically-significant LNRs that showed patterns of survival similar to those obtained from standard nodal staging.

Our findings suggest a significant prognostic value for LNR in colon and rectal cancer, possibly more so than the traditional nodal staging. Unlike the total yield of lymph nodes, LNR is less affected by the extent of mesocolic dissection, lymph node harvest, or neoadjuvant therapy. Moreover, our results highlight the inherent difference between colon cancer and rectal cancer, with different results arising when the combined cohort is examined. This adds to the growing body of evidence that the two entities behave independently and should hence probably be approached as different disease entities.

Mekki Medani fig1Figure 1: Illustration depicting the lymphatic network within the mesocolon

 

References

  1. Culligan K, Walsh S, Dunne C, Walsh M, Ryan S, Quondamatteo F, Dockery P, Coffey JC. The mescolon: a histological and electron microscopic characterization of the mesenteric attachment of the colon prior to and after surgical mobilization. Annals of Surgery; 2014 Jan 16 epub ahead of print
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