Abstract 5941: Impact of neoadjuvant treatment on the presence of perineural invasion in rectal cancer: a national analysis

Abstract Background: Perineural invasion (PNI) is an independent prognostic factor associated with lower overall and disease-free survival in rectal cancer patients. Several studies have established nomograms predicting PNI presence using clinical data and radiomics. These nomograms will help guide treatment for patients with high risk for PNI. There is limited data on the impact of neoadjuvant therapy on the presence of PNI in pathological specimens. This study assesses whether neoadjuvant treatment reduces the odds of PNI at the time of surgical resection. Methods: A retrospective analysis was conducted using the National Cancer Database, including patients aged ≥20 years diagnosed with rectal cancer from 2004 to 2020, with documented tumor stage and PNI status. Data collected encompassed demographics, tumor size and grade, TNM stage, and treatment sequences. Patients were categorized based on treatment sequence: surgical resection only (SRT), neoadjuvant treatment (NAT), adjuvant treatment (AT), and perioperative systemic therapy with neoadjuvant radiotherapy (PST/NART). Multivariable binary logistic regression analyzed the impact of neoadjuvant therapy on PNI presence, adjusting for significant covariates. Overall survival was assessed using multivariable Cox proportional hazards regression, adjusting for significant covariates. Results: Among 38, 537 patients, 25.3% received SRT, 38.7% NAT, 11.4% AT, and 24.6% PST/NART. In stage I, patients who received neoadjuvant treatment (NAT + PST/NART) were 50% less likely to have PNI compared to those who did not (SRT + AT) (P < 0.001). Stage II, III, and IV patients were 47%, 47%, and 40% less likely to have PNI with neoadjuvant treatment, respectively (all P < 0.001). In stage I, NAT patients had a 39% higher mortality risk compared to SRT patients (P < 0.001). In stages II and III, PST/NART patients had 38% and 34% lower mortality risks, respectively, compared to SRT patients (P = 0.003 and P < 0.001). In stage IV, AT patients had an 88% higher mortality risk compared to SRT patients (P = 0.049). Conclusion: Neoadjuvant treatment significantly reduces the presence of perineural invasion across all stages of rectal cancer, potentially improving survival outcomes, particularly in stages II and III. However, the increased mortality risk observed in stage I patients receiving neoadjuvant therapy indicates that benefits may not extend to early-stage disease, underscoring the need for careful patient selection and further prospective studies. Citation Format: Mohyeddine El Sayed, Sassine Youssef, Raymond N. Dubois. Impact of neoadjuvant treatment on the presence of perineural invasion in rectal cancer: a national analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5941.