Important role of lymphovascular and perineural invasion in prognosis of colorectal cancer patients with N1c disease

Abstract

Background: Lymphovascular invasion (LVI) and perineural invasion (PNI) are associated with decreased survival in colorectal cancer (CRC), but its significance in N1c stage remains to be clearly defined.

Aim: To evaluate LVI and PNI as potential prognostic indicators in N1c CRC.

Methods: We retrospectively identified 107 consecutive patients who had CRC with N1c disease radically resected at our hospital. Tumors were reviewed for LVI and PNI by one pathologist blinded to the patients' outcomes. Disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were determined using the Kaplan-Meier method, with LVI and PNI prognosis differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using log-rank test. The receiver operating characteristic (ROC) curve was used to evaluate the prognostic predictive ability.

Results: The median follow-up time was 63.17 (45.33-81.37) months for DFS, with 33.64% (36/107) of patients experiencing recurrence; 21.5% of tumors were found to be LVI positive and 44.9% PNI positive. The 5-year DFS rate was greater for patients with LVI-negative tumors compared with LVI-positive tumors (74.0% vs 35.6%), and PNI was similar (82.5% vs 45.1%). On multivariate analysis, LVI [hazard ratio (HR) = 3.368, 95% confidence interval (CI): 1.628-6.966, P = 0.001] and PNI (HR = 3.055, 95%CI: 1.478-6.313, P = 0.002) were independent prognostic factors for DFS. All patients could be divided into three groups of patients with different prognosis according to LVI and PNI. The 5-year ROC curve for LVI, PNI and their combination prediction of DFS was 0.646, 0.709 and 0.759, respectively. Similar results were seen for OS and CSS.

Conclusion: LVI and PNI could serve as independent prognostic factors of outcomes in N1c CRC patients. Patients with LVI or PNI should be given more attention during treatment.

Keywords: Colorectal cancer; Lymphovascular invasion; N1c; Perineural invasion; Prognosis.

Figure 1

Groups divided according to lymphovascular invasion or perineural invasion had different prognosis. A: Lymphovascular invasion (LVI) predicting disease-free survival (DFS) (P = 0.00011); B: LVI predicting overall survival (OS) (P < 0.0001); C: LVI predicting cancer-specific survival (CSS) (P < 0.0001); D: Perineural invasion (PNI) predicting DFS (P = 0.00011); E: PNI predicting OS (P < 0.0001); F: PNI predicting CSS (P = 0.00028). LVI: Lymphovascular invasion; PNI: Perineural invasion.

Figure 2

Three groups divided according to presence of lymphovascular invasion and perineural invasion had different prognosis. A: Predicting disease-free survival (P < 0.0001); B: Predicting overall survival (P < 0.0001); C: Predicting cancer-specific survival (P < 0.0001). LVI: Lymphovascular invasion; PNI: Perineural invasion.

Figure 3

Receiver operating characteristic curve on the predictive prognosis. A: Lymphovascular invasion (LVI) predicting disease-free survival (DFS); B: Perineural invasion (PNI) predicting DFS; C: LVI predicting overall survival (OS); D: PNI predicting OS; E: LVI predicting cancer-specific survival (CSS); F: PNI predicting CSS; G: Three groups predicting DFS; H: Three groups predicting OS; I: Three groups predicting CSS. LVI: Lymphovascular invasion; DFS: Disease-free survival; OS: Overall survival; CSS: Cancer-specific survival; AUC: Area under the receiver operating characteristic; PNI: Perineural invasion.