Association of neoadjuvant therapy with perineural invasion and postoperative survival in locally advanced colon cancer.

Abstract

e15634 Background: Perineural invasion (PNI) is a marker of aggressive tumor biology and adverse prognosis in colon cancer. The impact of neoadjuvant therapy on PNI and its relationship with postoperative survival remains poorly defined. Methods: We conducted a retrospective cohort study using the National Cancer Database including patients with clinically locally advanced, non-metastatic colon cancer (cT3-4, cN+, cM0) who underwent definitive resection between 2010 and 2022. Neoadjuvant therapy was defined as receipt of chemotherapy, immunotherapy, or radiation therapy prior to surgery. Multivariable logistic regression evaluated the association between neoadjuvant therapy and PNI. Overall survival (OS) was measured from surgery and analyzed using Cox proportional hazards models adjusted for baseline demographic, clinical, and tumor characteristics. Postoperative pathologic features were not included in primary survival models. Results: Among 15,471 patients, receipt of neoadjuvant therapy was independently associated with lower odds of PNI (aOR 0.56, p < 0.001). Neoadjuvant therapy was also associated with improved postoperative OS (HR 0.84, p = 0.001). In treatment-sequence sensitivity analyses, neoadjuvant therapy alone, adjuvant therapy alone, and combined neoadjuvant plus adjuvant therapy were associated with improved survival compared with surgery alone, with the greatest benefit observed among patients receiving combined therapy. In stratified analyses, neoadjuvant therapy was associated with improved survival among PNI-negative tumors, whereas in PNI-positive disease, survival benefit was primarily observed among patients receiving adjuvant or combined therapy. Conclusions: Neoadjuvant therapy is associated with reduced perineural invasion and improved postoperative survival in locally advanced colon cancer. In PNI-positive disease, survival benefit appears dependent on receipt of systemic therapy rather than neoadjuvant timing alone.