Perineural invasion is an independent predictor of outcome in colorectal cancer

Abstract

Purpose: Perineural invasion (PNI) is associated with decreased survival in several malignancies, but its significance in colorectal cancer (CRC) remains to be clearly defined. We evaluated PNI as a potential prognostic indicator in CRC, focusing on its significance in node-negative patients.

Patients and methods: We identified 269 consecutive patients who had CRC resected at our institution. Tumors were re-reviewed for PNI by a pathologist blinded to the patients' outcomes. Overall and disease-free survivals were determined using the Kaplan-Meier method, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test.

Results: PNI was identified in less than 0.5% of the initial pathology reports. On rereview, 22% of tumors in our series were found to be PNI positive. The 5-year disease-free survival rate was four-fold greater for patients with PNI-negative tumors versus those with PNI-positive tumors (65% v 16%, respectively; P < .0001). The 5-year overall survival rate was 72% for PNI-negative tumors versus 25% for PNI-positive tumors. On multivariate analysis, PNI was an independent prognostic factor for both cancer-specific overall and disease-free survival. In a subset analysis comparing patients with node-negative disease with patients with stage III disease, the 5-year disease-free survival rate was 56% for stage III patients versus 29% for patients with node-negative, PNI-positive tumors (P = .0002). Similar results were seen for overall survival.

Conclusion: PNI is grossly underreported in CRC and could serve as an independent prognostic factor of outcomes in these patients. PNI should be considered when stratifying CRC patients for adjuvant treatment.

Fig 1.

Incidence of perineural invasion (PNI) varies by tumor location. Tumors in the rectum had the highest PNI-positive rate (30%), followed by tumors in the right colon (25%) and left colon (22%). Tumors in the transverse colon and rectosigmoid showed the lowest frequency of PNI positivity (18% and 15%, respectively). These results did not reach statistical significance.

Fig 2.

Associations between perineural invasion (PNI) and established risk factors for poor outcome in colorectal cancer. PNI-positive rates increase with (A) advanced stage and (B) worsening tumor grade. (C) Patients with PNI-positive tumors are significantly more likely to have metastatic disease at diagnosis (five-fold increase compared with patients with PNI-negative tumors).

Fig 3.

Kaplan-Meier curves depicting (A) disease-free and (B) overall survival based on perineural invasion (PNI) status among 249 patients who underwent primary resection of their colorectal cancer, and Kaplan-Meier curves depicting (C) disease-free and (D) overall survival based on PNI status among 198 patients who underwent R0 resection of their colorectal cancer.

Fig 4.

Disease-free and overall survival of patients with R0 resections according to TNM stage and perineural invasion (PNI) status. (A) The 5-year disease-free survival rate was 56% for patients with stage III disease compared with 29% for patients with node-negative, PNI-positive disease (P = .0002). (B) Five-year overall survival rate was 67% for patients with stage III disease compared with 43% for patients with node-negative, PNI-positive disease (P = .002).