Observational Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2020; 12(5): 592-600
Published online May 15, 2020. doi: 10.4251/wjgo.v12.i5.592
Perineural invasion as a prognostic factor in patients with stage I-III rectal cancer – 5-year follow up
Milica Stojkovic Lalosevic, Tamara Milovanovic, Marjan Micev, Mirjana Stojkovic, Sanja Dragasevic, Milos Stulic, Ivan Rankovic, Vladimir Dugalic, Zoran Krivokapic, Aleksandra Pavlovic Markovic
Milica Stojkovic Lalosevic, Tamara Milovanovic, Mirjana Stojkovic, Sanja Dragasevic, Milos Stulic, Ivan Rankovic, Aleksandra Pavlovic Markovic, Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia, Belgrade 11000, Serbia
Milica Stojkovic Lalosevic, Tamara Milovanovic, Marjan Micev, Mirjana Stojkovic, Sanja Dragasevic, Milos Stulic, Ivan Rankovic, Vladimir Dugalic, Zoran Krivokapic, Aleksandra Pavlovic Markovic, School of Medicine, University of Belgrade, Belgrade 11000, Serbia
Marjan Micev, Vladimir Dugalic, Zoran Krivokapic, Clinic for Digestive Surgery - First Surgical Clinic, Clinical Center of Serbia, Belgrade 11000, Serbia
Author contributions: Stojkovic Lalosevic M and Milovanovic T reviewed the literature and contributed to manuscript drafting; Micev M contributed to study conception and design; Dugalic V and Krivokapic Z were the surgical team contributed to the review of the literature and final draft of the manuscript; Stulic M and Rankovic I contributed to manuscript drafting; Pavlovic Markovic A, Stojkovic M, Stojkovic Lalosevic M and were responsible for the revision of the manuscript for important intellectual content; all authors issued final approval for the version to be submitted.
Institutional review board statement: This study was approved by Institutional Ethical board (approval number 56-6, Clinical center of Serbia).
Informed consent statement: All study participants or their legal guardian gave informed consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement, and the manuscript was prepared and revised according to the STROBE Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Milica Stojkovic Lalosevic, MD, PhD, Assistant Professor, Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia; School of Medicine, University of Belgrade, Koste Todorovica 2, Belgrade 11000, Serbia. drmilicastojkovic@gmail.com
Received: December 30, 2019
Peer-review started: December 30, 2019
First decision: February 21, 2020
Revised: March 23, 2020
Accepted: April 18, 2020
Article in press: April 18, 2020
Published online: May 15, 2020
Abstract
BACKGROUND

Rectal cancer (RC) is one of the most common diagnosed cancers, and one of the major causes of cancer-related death nowadays. Majority of the current guidelines rely on TNM classification regarding therapy regiments, however recent studies suggest that additional histopathological findings could affect the disease course.

AIM

To determine whether perineural invasion alone or in combination with lymphovascular invasion have an effect on 5-years overall survival (OS) of RC patients.

METHODS

A prospective study included newly diagnosed stage I-III RC patients treated and followed at the Digestive Surgery Clinic, Clinical Center of Serbia, between the years of 2014–2016. All patients had their diagnosis histologically confirmed in accordance with both TMN and Dukes classification. In addition, the patient’s demographics, surgical details, postoperative pathological details, differentiation degree and their correlation with OS was investigated.

RESULTS

Of 245 included patients with stage I-III RC, lymphovascular invasion (LVI) was identified in 92 patients (38%), whereas perineural invasion (PNI) was present in 46 patients (19%). Using Kaplan-Meier analysis for overall survival rate, we have found that both LVI and PNI were associated with lower survival rates (P < 0.01). Moreover when Cox multiple regression model was used, LVI, PNI, older age, male gender were predictors of poor prognosis (HR = 5.49; 95%CI: 2.889-10.429; P < 0.05).

CONCLUSION

LVI and PNI were significant factors predicting worse prognosis in early and intermediate RC patients, hence more aggressive therapy should be reserved for these patients after curative resection.

Keywords: Lymphovascular invasion, Perineural invasion, Rectal cancer

Core tip: Perineural invasion alone is a strong predictor of poor survival of rectal cancer patients, however combined with lymphovascular invasion suggest even worse prognosis in these patients, even in early stages, hence adjuvant therapy should be administered in these cases.