Criteria for extramural perineural invasion as a prognostic factor in rectal cancer

Background: An abundant extramural autonomic nerve network is an anatomical feature of the rectum. Extramural perineural invasion (PNI) may influence the prognosis after resection of rectal cancer, however, few assessment criteria exist. Methods: PNI was investigated in 364 patients who underwent curative surgery for rectal cancer penetrating the muscular layer. A grading system was established based on the 'intensity' (number of PNI foci in a 20-power field) and 'depth' (distance from the muscularis propria) of PNI. PNI-0 was defined as without PNI, PNI-1 as 'intensity' of less than five foci and 'depth' less than 10 mm, and PNI-2 as five or more foci or 10 mm or greater 'depth' of invasion. Results: PNI was observed in 52 patients (14 per cent) and strongly correlated with pathological tumour node metastasis (pTNM) stage. Five-year survival was related to PNI grade (74 per cent in PNI-0, 50 per cent in PNI-1 and 22 per cent in PNI-2). The rate of local recurrence was also related to PNI stage: 43 per cent in PNI-2 and 9 per cent in both PNI-0 and PNI-1. Multivariate analyses showed that graded PNI was associated both with local recurrence and long-term survival, independent of tumour depth (pTNM T) and nodal involvement (pTNM N). Conclusion: The PNI grading system may be useful in prognosis and allow case selection for intensive postoperative adjuvant therapy.