Pathologically-based positive lymph node ratio (pLNR) for stage III colorectal cancer patients: prognostic impact on cases with fewer than 12 lymph node retrievals

Background: The pathologically-based positive lymph node ratio (pLNR) has been proposed as alternative lymph node (LN) parameters to the conventional TNM staging.

Objective: We evaluated the prognostic value of the pLNR for patients with stage III colorectal after curative surgery with adequate and inadequate LN retrieval (<12).

Materials and Method: A total of 258 patients with stage III colorectal adenocarcinoma who underwent curative resection performed in Phramongkutklao Hospital from January 1, 2003 through December 31, 2010 were given a regular follow-up according to established guidelines with routine physical examination, serum carcinoembryonic antigen (CEA), and colonoscopic surveillance. Imaging studies for detecting organ metastases were computed tomography (CT), magnetic resonance imaging, positron emission tomography (PET) CT scan, and ultrasonography. Patients were categorized into four groups according to the pathologically-based positive lymph node ratio (pLNR) (pLNR1: 0.1 to 0.25, pLNR2: 0.26 to 0.50, pLNR3: 0.51 to 0.75, and pLNR4: 0.76 to 1.0). Tumor-free survival was calculated from the date of primary colorectal tumor resection to the date of appearance of local recurrence or metastatic disease. The prognostic impact of pLNR was determined in the evaluated cohort and in a subgroup of patients with fewer than 12 LN retrievals who were examined.

Results: The number of LN examined ranged from 2 to 50 with a mean (SD) of 15.8 (8.7). In all, 93 (36%) patients with fewer than 12 LN were examined. Local recurrence or distant site metastases were found in 123 (47.7%) patients during the surveillance period with a median tumor-free survival of 41 months (95% CI, 28.7-53.3). Median tumor-free survival was categorized according to pLNR as follows: pLNR1 = 56 (95% CI, 36.3-75.7), pLNR2 = 22 (95% CI, 18.5-25.5), pLNR3 = 26 (95% CI, 10.5-70.9), and pLNR4 = 8 (95% CI, 1.1-5.8) months. Serum carcinoembryonic antigen (CEA) > 10 ng/dl, AJCC tumor stage 3C, and higher pLNR were found significantly associated with shorter tumor-free survival with univariate analysis. Potentially associated variables were then tested using multivariate analysis with a Cox regression model. This study found that the pLNR was the independent factor that was significantly associated with a risk of local recurrence or distant site metastases. In the evaluated cohort, the adjusted hazard ratio (HR) compared pLNR1 for pLNR2 = 2.27 (95% CI, 1.058-4.875; p < 0.01), pLNR3 = 4.365 (95% CI, 1.447-13.166; p < 0.05) and pLNR4 = 4.897 (95% CI, 1.546-15.518; p < 0.01). In the subgroup of patients with fewer than 12 LN retrievals who were examined, multivariate analysis was not consistently significant for all ranges of the adjusted hazard ration (HR) compared with pLN1 for pLNR3 = 10.552 (95% CI, 1.911-58.277; p < 0.05)

Conclusion: This study revealed pLNR was a significant independent prognostic factor that was associated with a risk of local recurrence or distant site metastases in patients with stage III colorectal cancer after curative surgery. A higher pLNR had a negative impact on tumor-free survival irrespective of the adequacy of LN retrieval.