Squamous cell carcinoma of the mandible – Patterns of metastasis and disease recurrence in dependence of localization and therapy

Abstract

Introduction

Oral squamous cell carcinomas exhibit distinct patterns of disease progression, depending on their localisation. This study aimed to evaluate clinicopathological data in patients with tumors of the mandibular alveolar process, to facilitate risk assessment and therapy planning.

Materials and methods

A retrospective cohort study was designed including patients with squamous cell carcinoma of the mandibular gingiva. Clinical and pathological data were collected to determine the rate of cervical metastases and clinical outcomes depending on tumor stage, localization (anterior, intermediate and posterior) and the extent of tumor resection.

Results

120 patients were included in the analysis. Rate of metastases was 42.6%. Tumors of the anterior part of the mandible exhibited significantly higher rates of bilateral metastases (anterior: 85.7%, intermediate: 15.8%, posterior: 4%, p < 0.001) and local recurrence (anterior: 25%, intermediate: 16.3%, posterior: 5.5%, p = 0.03) compared to posterior malignancies.

Conclusion

Tumors of the anterior segment of the mandible are characterized by high rates of metastases and local recurrence. Therefore, we propose radical segmental resection and bilateral neck dissection in those patients.

Introduction

Squamous cell carcinomas of the oral cavity (OSCC) form a major part within the group of head and neck squamous cell carcinomas (HNSCC) (Ferlay et al., 2010). Ranging among the eight most common malignant diseases worldwide, this entity is characterized by molecular and clinical heterogeneity (Alsahafi et al., 2019). The development of local disease recurrence and cervical and distant metastases has been shown to be the main prognostic factors in OSCC (Cooper et al., 2004; Akhtar et al., 2007; Pignon et al., 2009; D'Cruz et al., 2015). Surgical therapy is the established first-line standard of care and is combined with adjuvant radio- or radio-chemotherapy depending on tumor size and occurrence of metastases (Forastiere et al., 2001; Pignon et al., 2009; D'Cruz et al., 2015).

While in the past, OSCC were generally treated alike independent of their anatomic localization, lately evidence has grown showing that each subsite of the oral cavity exhibits distinct patterns of metastasis, disease recurrence and survival (Berger et al., 2015; Moratin et al., 2018, Moratin et al., 2019, Moratin et al., 2019).

Although several epidemiological studies presented clinical features of their investigated cohort, only a few have investigated the existence of site-specific relations between primary tumors, lymph node metastases and regional disease recurrence. Surgical tumor ablation in combination with elective neck dissection (ND) is regarded as the established first-line modality for the treatment of resectable OSCC. Nevertheless, radicalness and extent of the surgical procedures are a constant matter of debate. This applies especially for tumors located on or near the mandible. Here, surgical treatment options include either radical segmental resection or marginal resection. The surgeon often has to balance optimal oncological outcome and postoperative functionality and quality-of-life. Furthermore, there is no consistent standard in terms of uni- or bilateral neck dissection for patients with cN0 status. This may potentially lead to undertreatment in terms of insufficient primary and adjuvant therapy as e.g. postoperative radiation in most cases is being planned according to the pathological report. Even in pathologically confirmed cases of metastasis-free necks, bilateral ND improves adjuvant therapy as it is possible to reduce toxicity in these cases (Perkins et al., 2012; Spencer et al., 2014).

To avoid overtreatment with exaggerated surgical procedures and simultaneously achieve a maximum of oncological safety, there is an urgent need for preoperative risk assessment. This includes a rigorous validation of patients’ risk for the development of cervical metastases which has been shown to be influenced by the stage and localization of the primary tumor (Moratin et al., 2019, Moratin et al., 2019).

OSCCs located near the alveolar process of the mandible display an elevated risk of early bone infiltration. The specific rates of uni- or bilateral cervical metastases in dependence of T stage and sagittal localization of the primary tumor are crucial for therapy planning and the assessment of a patient's prognosis. Tumor removal including partial or segmental resection of the mandible is the established treatment (Brown et al., 2002; Rogers et al., 2004; Shaw et al., 2004; Mucke et al., 2011). Apart from achieving an optimal clinical outcome, preserving the patient's quality-of-life is a major goal in oncological therapy and mutilating surgical procedures should be limited to a minimum if possible. There are publications on clinical outcome depending on the extent of resection in patients with SCC located on the mandible (Brown et al., 2002; Wolff et al., 2004; Mucke et al., 2011). Nevertheless, the reported results and given recommendations are partly contradictory and there has not yet been a validation of different localizations within the mandible and their influence on metastasis and disease recurrence.

Therefore, the goal of this study was to investigate the incidence of regional metastases and patterns of disease recurrence in a cohort of patients with OSCC of the mandibular alveolar process in dependence of the sagittal tumor localization. Moreover, the prognostic impact of the extent of surgical therapy on clinical outcome was evaluated.