Lymph Node Ratio an Effective Indicator of Prognosis in Rectal Cancer

Lymph node ratio (LNR) may be a significant indicator of prognosis in patients with rectal cancer and could be used to better stratify patients in clinical trials, claims a recently published study. 

Conventional methods of cancer staging use the TMN system, which looks at how cancerous tumors have metastasized into a patient’s lymph nodes. However, this method is often contingent on the number of nodes a surgeon and histopathologist are able to retrieve. For this reason, LNR, which divides the number of metastatic nodes by the total number harvested, has been found to complement and even surpass TNM staging. 
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In a study published in Colorectal Disease, researchers led Alex Kartheuser, Cliniques Universitaires Saint-Luc (Brussels, Belgium), compared the effectiveness of LNR as an indicator of outcomes after treatment of rectal cancer with other known prognostic factors.

Using a prospectively maintained database, researchers identified 456 patients with non-metastatic disease who underwent surgery between 1998 and 2013. All patient characteristics, pre-operative investigation, surgical details, postoperative, and histopathological data were recorded. To be included for analysis, patients’ tumors had to be below 15 cm from the anal verge after endoscopic examinations. 

All patients underwent mesorectal excision and high and low anterior resection or abdominoperineal resection. Adjuvant chemotherapy was utilized if it was suggested by the medical oncologist and accepted by the patient. For lymph node retrieval, routine visual inspection, palpation, and dissection were the standard practice. Follow-up was performed every 3 to 6 months over a 5-year period, with colonoscopies scheduled 1 year after surgery, and then 3 to 5 years thereafter in the absence of significant findings. The primary outcome measure was overall survival (OS), though researchers also looked at overall recurrence-free survival (ORFS).

At analysis, 99 of 456 patients (21.7%) identified had some form of synchronous metastatic disease and had to be excluded from final review. Of the remaining 357 patients, most had mid- or low-rectal cancers (272 [76.2%]). Neoadjuvant radiotherapy or radiation therapy with concurrent chemotherapy was administered to 66.7% of patients. 

The mean number of nodes removed per patient was 12.8 (8.78), with 0.8 (7.97) of those being positive for cancer. The mean LNR was 0.074 (0.160). On average, a lower lymph node yield was observed in patients who received neodjuvant therapy. Statistical analysis also revealed that age, histological grade of differentiation, and chemoradiotherapy were also associated with the number of lymph nodes retrieved. 

Overall, 278 patients (77.9%) were still alive at the point of data cutoff. Although there was an insufficient number of events for researchers to estimate median overall survival, there was sufficient data to determine ORFS (139 months), 5-year ORFS (71.8%), and 5-year OS (80.1%). 

Results of a model evaluating how each clinical factor was associated with these outcomes found that the risk of death or recurrence was more than 4 times greater in patients with a LNR of 0.2. In addition, the selection of LNR was found to lead to a better and more stable statistical model for analyzing prognosis than other staging methods.

In their conclusion, the study authors wrote that LNR is, “one of the strongest prognostic factor[s] of overall survival and overall recurrence after treatment of rectal cancer.” The researchers suggested that LNR be used more consistently to stratify patients in clinical trials until more tumor-specific biomarkers become available in clinical practice. –Sean McGuire

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Leonard D, Remue C, Abbes Orabi N, et al. Lymph node ratio and surgical quality are strong prognostic factors of rectal cancer: results from a single referral centre [published online ahead of print April 29, 2016]. Colorectal Dis. doi: 10.1111/codi.13362.