Perineural invasion is an independent predictor of outcome in colorectal cancer

J Clin Oncol. 2009 Nov 1;27(31):5131-7. doi: 10.1200/JCO.2009.22.4949. Epub 2009 Sep 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / mortality*
  • Adenocarcinoma / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / therapy
  • Combined Modality Therapy
  • Digestive System Surgical Procedures
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Peripheral Nerves / pathology*
  • Prognosis
  • Radiotherapy
  • Radiotherapy, Adjuvant
  • Treatment Outcome


  • Antineoplastic Agents