The severity of neural invasion is a crucial prognostic factor in rectal cancer independent of neoadjuvant radiochemotherapy

Objective: To provide a comprehensive characterization of neural invasion (NI) in rectal adenocarcinoma (RC), to establish a novel NI-severity scoring system, and to assess the prognostic value of NI with emphasis on its localization and severity. Background: The literature merely contains small-scale studies with limited histopathological characterization of NI in RC. Methods: Neural invasion was thoroughly characterized in 296 patients with locally advanced uT3-RC (139 with primary resection and 157 with neoadjuvant radiochemotherapy [nRCTx]). To identify the precise localization of NI, we investigated the main tumor, peritumoral area, adjacent normal tissue, and all lymph nodes. To classify the clinical impact of NI, an NI severity score was established and related to patient prognosis. Results: Neural invasion was detected in 32% of patients with primary resection and in 19% (P = 0.010) receiving nRCTx. The major location of NI was found in the peritumoral area. The prevalence of NI in the main tumor within the primary resection group was 6%, whereas it was absent in the nRCTx group (P = 0.002). Increasing NI severity, but not NI localization, was associated with a significantly poorer survival and increased local recurrence rate in both groups. Multivariate analysis (including TNM-stage, grading, and Carcinoembryonic antigen (CEA)) revealed NI prevalence and severity as independent prognostic factors. Conclusions: Neural invasion in RC has a heterogeneous appearance in regard to its localization and its severity. nRCTx seems to have a suppressive effect on NI. Neural invasion severity might be applied as a novel tool to estimate accurately patient's prognosis and thus should be considered in pathology reports.