Predictors of locoregional control in stage I/II oral squamous cell carcinoma classified by AJCC 8th edition

doi:10.1016/j.ejso.2019.05.018

European Journal of Surgical Oncology

Volume 45, Issue 11, November 2019, Pages 2126-2130

https://doi.org/10.1016/j.ejso.2019.05.018 Get rights and content

Abstract

Objectives

To study the determinants of locoregional control (LRC) on stage I/II oral squamous cell carcinoma (OSCC) classified by AJCC 8th edition.

Methods

Retrospective analysis from 296 patients of pT1-2N0 oral OSCC treated with surgery (wide local excision and selective neck dissection). Those receiving adjuvant therapy were excluded. Multivariate analysis was performed for impact of adverse pathological features (APFs) on LRC.

Results

In stage I, LRC was impacted by perineural invasion (PNI) (HR 7.72, p = 0.010, 95% CI 1.64–36.26) and moderate/poor differentiation (MD/PD) (HR 3.04, p = 0.049, 95% CI 0.99–9.25). In stage II, LRC was impacted by depth of invasion (DOI) (HR 1.59, p = 0.014, 95% CI 1.099–2.32), PNI (HR = 2.86, p = 0.005, 95% CI 1.36–5.98). Combined MD/PD and PNI were associated with worse LRC than either feature individually (HR = 4.12, p < 0.001, 95% CI 2.16–7.85).

Conclusion

PNI and differentiation accurately predict LRC in AJCC 8th edition classified stage I/II OSCC. PNI was a stronger predictor of locoregional failure than DOI in stage II disease. By incorporating these parameters, we can improve precision in staging of early OSCC and identify potential candidates for treatment escalation to improve outcomes.

Section snippets

Background

The incorporation of depth of invasion (DOI) into TNM staging by the American Joint Committee on Cancer 8th edition [1] has resulted in a paradigm shift in pathological staging of oral squamous cell carcinoma (OSCC). Tumours having a DOI <5 mm have been designated as T1, those with a DOI of 5–10 mm T2 and those with DOI >10 mm as T3. Given that DOI is a superior predictor of disease specific survival than tumour diameter alone [2], it is possible that it is a surrogate marker for tumour

Materials and methods

From a prospectively maintained database of patients treated in our institution, Amrita Institute of Medical Sciences, Kochi, between 2006 and 2014, we identified 296 patients of OSCC (tongue, floor of mouth and buccal mucosa) classified as pT1-2N0 by AJCC 8th edition (those with diameter <2 cm and DOI ≤5 mm staged as pT1 and those with diameter 2–4 cm or DOI 6–10 mm staged as pT2). To avoid bias, we included consecutive patients; all patients treated during this period who fulfilled the

Patient and disease and characteristics

Patient, treatment and disease characteristics for our cohort of stage I/II OSCC is shown in Table 1. The median age of our patients was 55.2 years (range 18–78 years), with males accounting for 78% of our cohort. DOI correlated well with tumour diameter; for pT1 tumours (DOI<5 mm), mean diameter was 14.4 mm, while for pT2 tumours (DOI 6–10 mm), mean diameter was 26.7 mm. However, the median least tumour margin was comparable between the two groups - 7.86 mm and 7.84 mm for pT1 and pT2

Discussion

Reclassification of OSCC by AJCC 8th edition by incorporating DOI resulted in better prognostic grouping. This was reflected in a good stratification of APFs; stage II had a significantly higher association of LVI, PNI and poorer differentiation when compared with those having stage I disease.

As expected, DOI was an independent predictor of locoregional control on multivariate analysis, with node-negative tumours with DOI 5–10 mm having a 60% higher chance of locoregional failure than those

Conclusion

DOI alone is insufficient to predict LRC in early stage OSCC. Until other adverse features are integrated into the staging system, the prediction of LRC in early OSCC will be imprecise. Our results suggest that by incorporating PNI and differentiation into staging for early stage OSCC, patients at higher risk of locoregional failure are effectively identified for potential treatment escalation.

References (33)

A. Sparano et al.
Multivariate predictors of occult neck metastasis in early oral tongue cancer
Otolaryngol Head Neck Surg
(2004)
R. Dirven et al.
Tumor thickness versus depth of invasion–Analysis of the 8th edition American Joint Committee on Cancer Staging for oral cancer
Oral Oncol
(2017 Nov 1)
C.T. Liao et al.
Identification of a high-risk group among patients with oral cavity squamous cell carcinoma and pT1–2N0 disease
Int J Radiat Oncol Biol Phys
(2012)
Mahul B. Amin et al.
AJCC cancer staging manual
(2017)
A. Ebrahimi et al.
Primary tumor staging for oral cancer and a proposed modification incorporating depth of invasion: an international multicenter retrospective study
JAMA Otolaryngology–Head & Neck Surgery
(2014 Dec 1)
C.T. Liao et al.
Salvage therapy in relapsed squamous cell carcinoma of the oral cavity: how and when?
Cancer
(2008 Jan 1)
A. Ebrahimi et al.
Improved survival with elective neck dissection in thick early- stage oral squamous cell carcinoma
Head Neck
(2012)
S. Huang et al.
Predictive value of tumor thickness for cervical lymph-node involvement in squamous cell carcinoma of the oral cavity
Cancer
(2009)
F.M. Fang et al.
Combined modality therapy for squamous cell carcinoma of the buccal mucosa: treatment and prognostic factors
Head Neck
(1997)
G. El-Husseiny et al.
Squamous cell carcinoma of the oral tongue: an analysis of prognostic factors
Br J Oral Maxillofac Surg
(2000)

H. Low et al.

Factors predicting poor outcomes in T1N0 oral squamous cell carcinoma: indicators for treatment intensification

ANZ J Surg

(2016)

Tumours and cysts of the dermis

J.J. Fagan et al.

Perineural invasion in squamous cell carcinoma of the head andneck

Arch Otolaryngol Head Neck Surg

(1998)

D. Vuity et al.

Is the 8th edition of the Union for International Cancer Control staging of oral cancer good enough?

Br J Oral Maxillofac Surg

(2018 Mar 22)

W.M. Lydiatt et al.

Head and neck cancers—major changes in the American Joint Committee on cancer eighth edition cancer staging manual.CA

A Cancer Journal for Clinicians

(2017)

A. Almangush et al.

Depth of invasion, tumor budding, and worst pattern of invasion: prognostic indicators in early-stage oral tongue cancer

Head Neck

(2014)

Cited by (19)

Controversies in the treatment of early-stage oral squamous cell carcinoma
2024, Current Problems in Cancer
The treatment of early-stage oral squamous cell carcinoma (OSCC) is still a controversial issue. Thanks to the 8^th edition of TNM by AJCC there is a better distinction between the stages of OSCC. However, Stages I and II still share the same treatment protocol, even if the prognosis is radically different. A retrospective study has been conducted including 70 previously untreated patients with Stage I or II OSCC, treated with tumorectomy and selective neck dissection. The study focuses on the link between pT1/2 and various other factors, particularly histological grading, vascular and perineural invasion, local and cervical recurrence, surgical margins and overall survival. These data reveal significant differences between pT1 and pT2 in histological grade, perineural invasion, cervical recurrence, surgical margins, and overall survival, emphasizing the necessity of different treatment protocols for T1 and T2 OSCC. Distinct strategies should be proposed to treat Stage I and II OSCC, with Stage II patients possibly benefitting from more aggressive treatments: following these data, a wait-and-see strategy should only be considered in Stage I, while certain treatments at the cervical level — such as prophylactic neck dissection and sentinel node biopsy — should always be considered for Stage II tumors.
AIRO GORTEC consensus on postoperative radiotherapy (PORT) in low-intermediate risk early stages oral squamous cell cancers (OSCC)
2022, Radiotherapy and Oncology
Citation Excerpt :
Early-stage OSCCs should ideally be treated with surgery as a single therapeutic modality. Locoregional recurrence rates after margin-free surgical resections range between 16 and 20 % [1920]. Ensuring resection within large (1 cm) free surgical margins ab initio is sometimes challenging due to the complex oral anatomy and the need to preserve vital anatomical structures, oral function, and quality of life.
Evidence on the efficacy of postoperative radiotherapy (PORT) in low-intermediate risk squamous cell carcinoma of the oral cavity (OSCC) remains inconclusive.
Members of a task force from two national radio-oncology Associations (AIRO and GORTEC) defined 14 clinically relevant questions to identify “gray areas” pertinent to the indication for PORT in this clinical setting.
Consequently, a literature review was performed on the topic. The resulting statements were then rated by an Expert Panel (EP) using a modified Delphi method. Only radiation oncologists were part of the discussion and voting on the scenarios.
There was agreement on the 14 statements at the first round of voting. The task force then decided to propose clinical cases for the two more controversial statements that had received a lower agreement to better capture the Experts' attitudes. The clinical cases highlighted a more significant decisional heterogeneity. However, the good level of consensus reached among the two Associations gives relevant support in informing clinical choices while acknowledging general indications cannot fit all clinical situations and do not replace multidisciplinary discussion.
Oncological outcomes of compartmental surgery and wide local excision in oral tongue and floor of the mouth cancer
2022, Oral Oncology
Citation Excerpt :
The inclusion of depth of invasion (DOI) in the 8th Edition of the TNM staging systems for oral cancer [6] improved its prognostic performance [7,8]. However, one-third of OTSCC with a DOI < 10 mm can develop loco-regional recurrences [9], which has been noted to have a strong correlation with adverse pathological features such as perineural (PNI), lympho-vascular invasion (LVI), degree of differentiation, and pattern of invasion [10,11]. A recently validated nomogram for OTSCC confirmed the prognostic impact of these parameters on overall (OS) and disease-specific survivals (DSS) [12].
Oral tongue carcinomas represent more than half of the tumors arising in the oral cavity, a site with a high cancer specific mortality and impact on quality of life. Current guidelines are lacking for a standardized surgical approach of these tumors. The aim of this study is to compare two currently adopted surgical strategies, compartmental surgery (CTS) and wide local excision (WLE), with loco-regional control as the main oncological endpoint.
An observational retrospective multicentric study was carried out enrolling a cohort of patients affected by oral tongue or floor of the mouth squamous cell carcinoma and surgically treated in 4 international tertiary referral centers. Survival analysis was performed by propensity-score matching approach and multivariable Cox regression analysis.
A cohort of 933 patients was enrolled. CTS was applied in 113 patients (12.1%) and WLE in 820 (87.9%). Analyzing a propensity-score matched cohort (98 CTS vs. 172 WLE) and applying a survival multivariable modeling strategy on the whole cohort, both confirmed that CTS and WLE are comparable and oncologically safe. Parameters such as number of positive lymph nodes, depth of invasion, and lymphovascular invasion still represent the key prognosticators.
The main goals for surgical resection of oral cancer remain its three-dimensional circumferential clearance with adequate margins and en-bloc removal of the tumor-lymph node tract, independently of the technique adopted (CTS or WLE). Further prospective studies including quality of life evaluation are needed to better understand if one of these approaches can provide superior functional outcomes.
Early-onset oral cancer as a clinical entity: aetiology and pathogenesis
2022, International Journal of Oral and Maxillofacial Surgery
Citation Excerpt :
Young adults with head and neck carcinoma have a significantly advanced N stage and rate of perineural invasion.11,19 Locally advanced OSCC with a depth of invasion>5 mm and damage to the bone structures, muscles, and neck tissues shows a poor prognosis.20,21 Metastases in regional lymph nodes, their size, number, and extracapsular spread are proven factors that worsen the prognosis of OSCC.18,20
Oral squamous cell carcinoma (OSCC) is one of the most important medical and socio-economic problems in many of the developed countries worldwide, due to the high mortality. The incidence of OSCC among individuals under 45 years of age is growing every year; however, the aetiological factors and pathogenetic mechanisms are poorly understood. This review summarizes the available information regarding clinicopathological features, extrinsic and intrinsic aetiological factors, and the molecular and immune landscape of early-onset OSCC. This cancer shows high recurrence rates and is not associated with the aetiological factors specific to adult-onset OSCC. Young adults with OSCC are not infected with human papillomavirus and rarely consume alcohol or tobacco, but more frequently use smokeless tobacco. Data from single studies indicate the hereditary nature of early-onset OSCC: the KIR2DL1⁺-HLA-C2⁺ genotype and MMP-1 2 G allele are frequently detected in young patients. Early-onset OSCC shows specific genetic, epigenetic, transcriptomic, and proteomic changes. The tumour microenvironment in early-onset OSCC is tolerogenic rather than immunogenic. All of the data suggest that OSCC in young patients is a separate clinical entity with a specific aetiology and pathogenesis. Further studies are needed to reveal the causes and molecular targets of early-onset OSCC for the development of preventive and therapeutic strategies.
A critical evaluation of computed tomography-derived depth of invasion in the preoperative assessment of oral cancer staging
2020, Oral Oncology
Citation Excerpt :
Of note, recent work has demonstrated that in the presence of pDOI ≤ 4 mm, the risk of regional failure is very low even if other adverse features are present [28]. Other authors have instead found that DOI alone is not sufficient to predict recurrence in early-stage OSCC but, again, rDOI is one of the few parameters that could be obtained before surgery [29,30]. Even though the pathological assessment of DOI is considered the “gold standard”, its evaluation is not without issues [4,31].
Depth of invasion (DOI) has been introduced into the latest TNM classification of oral squamous cell carcinoma (OSCC). Despite its primarily pathological definition (pDOI), a preoperative evaluation of a radiological DOI (rDOI) would be useful but a standard and practical definition is lacking. The primary aim of this study is to measure the rDOI by computed tomography (CT) and compare it to the pDOI in a cohort of OSCC patients. Then, we analyze the utility and reliability of rDOI in the preoperative setting.
58 cases of OSCC operated at our Institution from 2016 to 2019 were included. After accounting for plane-specific shrinkage factors and for different oral subsites, we have compared pDOI and rDOI for each spatial plane by paired difference test and correlation coefficient. Radiological accuracy and survival analysis were also determined to identify rDOI’s clinical value.
For lateral tongue, pDOI was more strongly related with axial rDOI (P < 0.01); for hard palate, the best plane was the sagittal one (P < 0.01); in floor of mouth (FOM) lesions, the strongest correlation was with coronal rDOI (P < 0.01), as well as for cheek buccal mucosa; sagittal scans seem to be the best to evaluate dorsum of the tongue and retromolar trigone; gingiva (P < 0.01) was most correctly evaluated in the coronal plane. Overall accuracy of rDOI restaging was 75.41%. Disease-free survival seems to be worse as rDOI increases.
We suggest that with a standardized imaging protocol patients could be better classified according to CT-derived DOI.
Perineural Invasion Is a Significant Prognostic Factor in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
2023, Diagnostics

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View full text

Predictors of locoregional control in stage I/II oral squamous cell carcinoma classified by AJCC 8th edition

Abstract

Objectives

Methods

Results

Conclusion

Section snippets

Background

Materials and methods

Patient and disease and characteristics

Discussion

Conclusion

Otolaryngol Head Neck Surg

Oral Oncol

Int J Radiat Oncol Biol Phys

AJCC cancer staging manual

Primary tumor staging for oral cancer and a proposed modification incorporating depth of invasion: an international multicenter retrospective study

JAMA Otolaryngology–Head & Neck Surgery

Salvage therapy in relapsed squamous cell carcinoma of the oral cavity: how and when?

Cancer

Improved survival with elective neck dissection in thick early- stage oral squamous cell carcinoma

Head Neck

Predictive value of tumor thickness for cervical lymph-node involvement in squamous cell carcinoma of the oral cavity

Cancer

Combined modality therapy for squamous cell carcinoma of the buccal mucosa: treatment and prognostic factors

Head Neck

Squamous cell carcinoma of the oral tongue: an analysis of prognostic factors

Br J Oral Maxillofac Surg

Factors predicting poor outcomes in T1N0 oral squamous cell carcinoma: indicators for treatment intensification

ANZ J Surg

Tumours and cysts of the dermis

Perineural invasion in squamous cell carcinoma of the head andneck

Arch Otolaryngol Head Neck Surg

Is the 8th edition of the Union for International Cancer Control staging of oral cancer good enough?

Br J Oral Maxillofac Surg

Head and neck cancers—major changes in the American Joint Committee on cancer eighth edition cancer staging manual.CA

A Cancer Journal for Clinicians

Depth of invasion, tumor budding, and worst pattern of invasion: prognostic indicators in early-stage oral tongue cancer

Head Neck