Elsevier

Surgical Oncology

Volume 27, Issue 2, June 2018, Pages 123-128
Surgical Oncology

Prognostic impact of perineural invasion in early stage oral tongue squamous cell carcinoma: Results from a prospective randomized trial

https://doi.org/10.1016/j.suronc.2018.02.005Get rights and content

Highlights

  • Perineural invasion (PNI) predicted cervical metastasis and poor survival outcomes of cT1-2N0 tongue cancer patients.

  • PNI presence correlated with poor differentiation and associated with depth of invasion of the cT1-2N0 tongue cancer.

  • Elective neck dissection could not improve benefits compared to observation for the PNI-positive patients in our trial.

Abstract

Background

Although perineural invasion (PNI) has been recognized as a poor prognostic factor for oral cancer, few studies have focused on tongue squamous cell carcinoma (TSCC). Using a prospective randomized trial, this study investigated the role of PNI in the regional control and survival of the patients with cT1-2N0 TSCC, and clarified the benefit of neck management based on PNI status.

Methods

PNI status was reviewed under H&E staining in tumors of 221 patients with cT1–2N0 TSCC, who were randomly assigned into elective neck dissection (END) group (n = 111) and observation group (n = 110). Oncologic and survival outcomes were analyzed by multivariate regression and Kaplan–Meier analyses.

Results

PNI was identified in 34 patients and multivariate analyses revealed that PNI remained an independent predictor for cervical lymph node metastasis (CLNM), local relapse, neck relapse and disease-specific survival (DSS) after controlling for T stage and pathologic differentiation. END could not improve the benefit for patients. Stratified analysis revealed that END also could not improve neck control or DSS among patients with PNI.

Conclusions

This study demonstrated that PNI was an invaluable pathological parameter to independently predict cervical metastasis, local relapse, neck relapse and poor survival outcomes, but END could not improve benefits compared to observation for the PNI-positive patients.

Introduction

Tongue squamous cell carcinoma (TSCC) is the most common oral cancer, which is the eighth most frequent cancer-related death worldwide [1]. TSCC is well known for its high propensity to metastasize to cervical lymph nodes, even for clinical T1-2 tumors and node-negative necks (cT1-2N0) amenable for local surgical excision and neck dissection [2]. In patients with TSCC, the presence of cervical lymph node (LN) metastasis is the most important prognostic factor of survival, and regional recurrence after surgical excision is the most frequent cause of treatment failure and poor outcomes [3]. Therefore, the studies are need for exploring novel techniques or pathological indicators that effectively predict LN involvement or neck relapse, and that are capable of guiding optimal neck management for individual patients with TSCC.

Perineural invasion (PNI) is a distinct pathological feature characterized by the presence of tumor cells within the nerve sheath or perineural space [4]. According to the protocol published by the College of American Pathologists, PNI status is a required feature of the regular pathology report for oral cancer [5]. PNI is also regarded as an adverse feature in the National Comprehensive Cancer Network guidelines for head and neck cancers [6]. Although PNI has been recognized as a poor prognostic factor in several human cancers including oral and head and neck cancers [[7], [8], [9], [10], [11]], it remains unclear whether differential prognostic significance of PNI can be observed at different subsites and tumor stages of head and neck cancer. Besides, the specific impact of PNI on oncologic outcomes and survival also remains controversial [9,10]. Thus, it is important to clarify the impact of PNI at specific early-stage TSCC in order to better understand and properly apply this commonly used pathologic parameter in head and neck cancers.

In this study, we therefore focused specifically on the impact of PNI in early-stage TSCC. We aimed to investigate the roles of PNI and other parameters in the LN involvement, loco-regional control, and survival of the patients with cT1-2N0 TSCC, and clarify the benefit of neck management based on PNI status used a prospective randomized trial from China.

Section snippets

Study patients

The studied subjects who were enrolled onto a prospective randomized single-center trial from the Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, China were eligible for this study. The primary objective of the trial was to estimate the patients with early-stage cT1-2N0 TSCC should be treated with elective neck dissection (END) at the time of the primary surgery or observed with therapeutic neck dissection (TND) after neck metastasis. The trial was

END could not improve the benefit compared to observation for the cT1/2N0 TSCC patients

A total of 221 cT1–2N0 TSCC patients were randomly assigned into END group (n = 111) and observation group (n = 110). Clinicopathological features and outcomes of the cT1/2N0 TSCC patients by neck management are shown in Table S1. There were no significant differences in age, sex, T stage, and pathological grade between the observation and END groups (all P > 0.05). The differences in oncologic outcomes including LN metastasis, tongue local relapse, neck relapse, and distant metastasis were not

Discussion

Oral TSCC is increasingly accepted as a biologically different entity compared to carcinoma affecting other oral subsites, with TSCC being more aggressive and generally associated with a higher rate of metastasis [2]. The elective neck management of the cT1-2N0 TSCC has been the subject of much debate during the past three decades and continues to be controversial [12]. This is partly because of the relative paucity of prospective studies and the lack of randomized trials in this population,

Acknowledgements

This work was partially supported by National Natural Science Foundation of China (81602367), Science and Technology Commission of Shanghai Municipality (15411950300) and Shanghai Summit & Plateau Disciplines.

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