Extramural perineural invasion in pT3 and pT4 rectal adenocarcinoma as prognostic factor after preoperative chemoradiotherapy

Perineural invasion (PNI) is widely studied in malignant tumors, and its prognostic significance is well demonstrated in the head and neck and prostate carcinomas, but its significance in rectal cancer is controversial. Most studies have focused on evaluating mural PNI (mPNI); however, extramural PNI (ePNI) may influence the prognosis after rectal cancer resection. We evaluated the prognostic value of ePNI compared with mPNI and with non-PNI, in rectal resections after preoperative chemoradiotherapy in 148 patients with pT3 and pT4 rectal carcinomas. PNI was identified in 35 patients (23.6%), 60% of which were in the mPNI group. Factors associated with PNI were tumor invasion depth, lymph node metastasis, lymphovascular invasion, and venous invasion; patients with PNI were more likely to have positive resection margins (65.7% versus 11.6%). ePNI, compared with mPNI, was associated with female sex (64.3% versus 28.6%), positive surgical margins (42.8% versus 28.6%), recurrence (50% versus 28.6%), and death (92.9% versus 28.6%). The 5-year disease-specific survival rate was 78.1% for patients without PNI, compared with 63.7% for the mPNI group and 26.4% for the ePNI group (P<.001). On multivariate analysis, the independent adverse prognostic factors were ePNI (odds ratio [OR], 22.17; 95% confidence interval [CI], 17.03-24.58; P<.001), overall recurrence (OR, 9.19; CI, 6.11-10.63; P=.002), clinical stage IV (OR, 8.56; CI, 6.34-9.47; P=.003), and positive surgical margin (OR, 3.95; CI, 2.00-4.28; P=.047). In conclusion, we demonstrated the prognostic effect of ePNI for disease-specific survival in surgically resected pT3-pT4 rectal cancer patients with preoperative chemoradiotherapy.