The prognostic value of combining the CD8+lymphocyte density and the circulating lymphocyte ratio in circumferential resection margin biopsy in rectal cancer

Background: A positive circumferential resection margin (CRM) may result in local recurrence (LR), but the significance remains controversial. We attempted to utilize the lymphocyte ratio (LYMR), neutrophil-lymphocyte ratio (NLR), tumor-infiltrating lymphocyte (TIL) count, and their combinations (TIL-LYMR/TIL-NLR) in predicting LR after rectal resection. Methods: Patients with rectal cancer who underwent curative resection between January 2016 and December 2018 were enrolled. Biopsy samples and data from the blood tests of 124 patients with rectal cancer who underwent curative resection were retrospectively obtained. Patients were divided into 2 groups: LR group and non-local recurrence (nLR) group. CD8+ TILs were immunostained using an antibody against CD8. The density of TILs was defined as the number of positive CD8 lymphocytes per square millimeter and was then graded as either high or low (cutoff=80/mm(2)). The count of LYMR and NLR was also graded as either high or low. The associations between TILs, LYMR, NLR, and their combinations (TIL-LYMR/TIL-NLR) were evaluated. Results: With a median follow-up of 24.4 months, TIL-LYMR showed a positive correlation with LR (P=.001), but not with the CD8 + TIL count (P=.215) or TIL-NLR count (P=.638). Among inflammatory and immune markers variables, univariate analysis revealed that gender, CD8+ TIL count, and TIL-NLR count were associated with anastomotic leakage (P=.001, P=.014, and P=.036, respectively). In multivariate analysis, TIL-LYMR remained an independent predictor of LR (OR=8.918, CI=1.124-70.747, P=.038). We also showed that gender associated with anastomotic leakage in rectal cancer (OR 5.429; 95% CI 1.885-15.637; P=.002). Conclusion: In this study, our data indicate that absence of CD8+ T-cell infiltration in CRM may influence LR. These parameters may help identify LR provide additional information for therapeutic decision-making.