Predicting Perineural Invasion in CRC: Surgery | April 2026

Perineural invasion (PNI) is a well-recognized adverse prognostic factor in colorectal cancer (CRC), associated with aggressive tumor biology, higher metastatic potential, and poor survival outcomes. However, PNI is typically identified only after surgical resection on histopathology. The ability to predict PNI preoperatively could significantly influence risk stratification, surgical planning, and decisions regarding neoadjuvant or adjuvant therapy.

Problem Statement

Currently, there is no reliable preoperative tool to predict perineural invasion in colorectal cancer. This limits the ability to identify high-risk patients early and incorporate this critical prognostic factor into multidisciplinary decision-making before definitive treatment.

Summary

This large SEER-based case-control study involving over 223,000 CRC patients identified key predictors of PNI, including male sex, tumor location (left colon and rectum), poor differentiation, nodal involvement (N1/N2), and elevated carcinoembryonic antigen levels. PNI was present in 13.1% of cases and was strongly associated with worse 5-year overall and cancer-specific survival, as well as increased liver and lung metastases. The derived Cleveland Clinic Florida PNI prediction score demonstrated excellent negative predictive value (93%), making it particularly useful to rule out PNI preoperatively. This model has potential clinical utility in guiding personalized treatment strategies and improving multidisciplinary planning in colorectal cancer.