Prognostic impact of perineural invasion in early stage oral tongue squamous cell carcinoma: Results from a prospective randomized trial
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.
References (26)
Global epidemiology of oral and oropharyngeal cancer
Oral Oncol.
(2009)- et al.
Perineural growth in head and neck squamous cell carcinoma: a review
Oral Oncol.
(2015) - et al.
The role of perineural invasion in treatment decisions for oral cancer patients: a review of the literature
J. Cranio-Maxillo-Fac. Surg.
(2017) - et al.
Perineural invasion in oral squamous cell carcinoma: a discussion of significance and review of the literature
Oral Oncol.
(2011) - et al.
Impact of perineural invasion as independent prognostic factor for local and regional failure in oral squamous cell carcinoma
Oral Surg Oral Med Oral Pathol Oral Radiol
(2015) - et al.
Neck observation is appropriate in T1-2, cN0 oral squamous cell carcinoma without perineural invasion or lymphovascular invasion
Oral Oncol.
(2014) - et al.
The role of neck dissection and postoperative adjuvant radiotherapy in cN0 patients with PNI-positive squamous cell carcinoma of the oral cavity
Oral Oncol.
(2014) - et al.
A clinicopathological study of perineural invasion and vascular invasion in oral tongue squamous cell carcinoma
Int. J. Oral Maxillofac. Surg.
(2015) - et al.
Analysis of inflammatory infiltrate, perineural invasion, and risk score can indicate concurrent metastasis in squamous cell carcinoma of the tongue
J. Oral Maxillofac. Surg.
(2012) - et al.
Survival pattern and prognostic factors of patients with squamous cell carcinoma of the tongue: a retrospective analysis of 210 cases
J. Oral Maxillofac. Surg.
(2013)
Early tongue carcinoma: analysis of failure
Head Neck
Early stage squamous cell cancer of the oral tongue–clinicopathologic features affecting outcome
Cancer
Perineural invasion in cancer: a review of the literature
Cancer
Cited by (40)
Management of clinically node-negative early-stage oral cancer: network meta-analysis of randomized clinical trials
2024, International Journal of Oral and Maxillofacial SurgeryStiffness as measured with strain elastography is a prognostic factor for pT1/T2 tongue squamous cell carcinoma with muscle-layer invasion
2023, Oral Surgery, Oral Medicine, Oral Pathology and Oral RadiologyOncological outcome of contralateral submental artery island flap versus primary closure in tongue squamous cell carcinoma: randomized non-inferiority clinical trial
2023, International Journal of Oral and Maxillofacial SurgeryTumor–stroma ratio is a crucial histological predictor of occult cervical lymph node metastasis and survival in early-stage (cT1/2N0) oral squamous cell carcinoma
2022, International Journal of Oral and Maxillofacial SurgeryDeterminants of prognosis in patients with oral squamous cell carcinoma metastasizing to a single cervical lymph node
2021, Oral OncologyCitation Excerpt :We observed in our cohort that PNI was the only tumour factor that was consistently associated with poor OS and DFS on multivariate analysis. In a randomized controlled trial investigating its prognostic impact, PNI was found on stratified analysis to predict cervical lymph node metastasis, local failure and poor survival [18]. It has been suggested that the size of tumour deposit reflects the disease burden better and may be a reliable gauge of disease biology and ultimately the prognosis [3].
Is Perineural Invasion a Reasonable Indicator for Neck Dissection in cT1N0M0 Squamous Cell Carcinoma of the Oral Cavity?
2021, Journal of Oral and Maxillofacial SurgeryCitation Excerpt :However, they found adjuvant radiotherapy showed improvement in survival with PNI patients. Finally, Lanzer et al advocated for radiotherapy for PNI patients.4,12 The overall inconsistencies in the literature have led to a lack of consensus regarding patients with tumors with PNI involving small nerves being treated with adjuvant radiation.12
- 1
These authors contributed equally to this work.