Management of early oesophageal cancer: An overview

Abstract

The incidence of esophageal cancer, namely the adenocarcinoma subtype, continues to increase exponentially on an annual basis. The indolent nature of the disease renders a significant proportion inoperable at first presentation, however, with the increased utilisation of endoscopy, many early lesions are now being identified which are suitable for endotherapeutic approaches. This article details the options available for dealing with early esophageal cancer by endoscopic mean obviating the need for surgery thereby avoiding the potential morbidity and mortality of such intervention.

Key Words: Esophageal cancer; Endotherapy; Endoscopic submucosal resection; Endoscopic mucosal resection; Endoscopy

Core Tip: Endoscopic treatment approaches have been adopted in managing early esophageal cancer in recent years. Endoscopic mucosal resection and endoscopic submucosal dissection are now considered at multidisciplinary discussions. Both are viable options and have replaced esophagectomy as the preferred treatment modality in certain cases as they are associated with reduced morbidity and mortality rates. Endotherapy is now the key treatment for early esophageal cancer with no compromise to oncological outcomes.

INTRODUCTION

Oesophageal cancer poses a significant global health challenge with over 600000 new diagnoses and 540000 deaths annually[1]. In recent years, there has been a shift in the histological subtype seen in Europe and North America from squamous cell carcinoma (SCC) to adenocarcinoma[2]. The overall 5-year relative survival rate is around 20% but, if diagnosed early, outcomes can be significantly improved with cure rates of successfully treated early oesophageal cancer of over 80%[3,4]. Traditionally, oesophagectomy was the treatment modality of choice but is associated with high morbidity rates and potential mortality[5]. In recent years endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have offered a more favourable approach where suitable with comparable oncological outcomes[6]. This scientific paper provides an overview of the current literature surrounding the management of early oesophageal cancer. We aim to shed light on recent developments in diagnostic modalities, treatment strategies, and prognostic factors influencing the management of this disease.

Clinical work-up is required to accurately diagnose and stage oesophageal cancer to determine an appropriate treatment plan. Pre-treatment evaluation includes locoregional staging to assess the extension of the tumour into the oesophageal wall along with lymph nodes. Before employing an endoscopic treatment approach, it is important that there is negligible lymph node metastasis (LNM) and that an en bloc resection with negative margins is achievable. There is a significantly increased incidence of nodal disease with advancing T stage[7]. The oesophagus consists of three mucosal layers (epithelium, lamina propria, and muscularis mucosa) and a deeper submucosal layer made of connective tissue. The submucosa connects the mucosa to the muscularis propria. This consists of an inner circular muscle layer, outer longitudinal muscle layer and the Auerbach plexus. Invasion of the mucosa and submucosa is described as T1a and T1b disease respectively. T1a tumours have a negligible rate of regional disease on pathology compared with 16%-41% in T1b tumours[8-10]. Therefore, it is paramount to establish the exact level of invasion of the oesophageal wall. T1a invasion is further subcategorised into the deepest layer of mucosa involved; epithelium (m1), lamina propria (m2), and muscularis propria (m3). Likewise, T1b is subcategorised into inner third (sm1), middle third (sm2), and outer third (sm3) invasion of the submucosa.

As alluded to already, surgical resection has been the traditional curative treatment method in oesophageal cancer for years but endoscopic therapy is now increasingly the established gold standard in early carcinomas if there is no lymph node involvement. Other factors associated with LNM include tumour size > 2 cm and poor differentiation[9] and these would be considered along with the extent of oesophageal wall invasion at multidisciplinary discussions. Scoring algorithms have been described to predict patients most at risk of LNM to aid the decision-making process for endoscopic resection in patients with T1 oesophageal adenocarcinoma[11].

Clinically apparent regional and distant disease often require investigations such as cross-sectional imaging, positron emission tomography (PET) scans and endoscopic ultrasound (EUS) to appropriately stage the disease. The Society of Thoracic Surgeons published guidelines on staging oesophageal cancer[12]. PET scans detect metastatic disease in 15%-20% of patients and supplements computed tomography imaging in this regard[13]. Moreover, PET imaging has been shown to have prognostic value and aids treatment decision-making. EUS aids locoregional staging in the absence of distant metastasis and can guide treatment planning. This is particularly relevant in early oesophageal cancer as EUS has a reported sensitivity and specificity of 81.6% and 99.4% respectively for staging T1 tumours[14]. This is enhanced by the use of fine-needle aspiration or fine-needle biopsy along with EUS[15]. Chromoendoscopy and advanced endoscopic imaging techniques may also be employed where appropriate. For example, dye stains such as Lugol’s iodine and acetic acid may be used for SCC and Barrett’s esophagus respectively, while Narrow Band Imaging enables detailed evaluation of lesions.

EMR is one of the main endoscopic treatment options in early oesophageal cancer. It has replaced oesophagectomy as the treatment approach of choice in high-grade dysplastic Barrett’s oesophagus, intramucosal cancer and sometimes in early invasive cancer if there is a low risk of LNM[16]. Although higher cure rates are achieved with oesophagectomy, the significant incidence of morbidity and mortality associated with this procedure must be considered at multidisciplinary discussions. Moreover, patients with a number of co-morbidities may not be suitable candidates for surgery. Curative endoscopic resection is achievable for mucosal carcinomas with comparable outcomes in adenocarcinomas and early SCCs and is now the first line treatment option in ‘superficial’ cancers as seen on endoscopy. EMR is limited by its inability to resect large lesions en bloc but is a simpler and faster technique than ESD. This is because there is a high rate of recurrence if EMR is performed on large lesions[17]. Moreover, histopathologic evaluation of tissue specimens to accurately stage a lesion and assess for R0 resection can be quite difficult.

EMR is highly efficacious in treating Barrett’s oesophagus-related adenocarcinoma and thus, there is a limited role for ESD in these cases. Endoscopic ablation of Barrett’s oesophagus is employed in patients with high-grade dysplasia with no visible lesion. However, EMR is the treatment of choice where this a visible neoplasia. This is because there is no significant difference between EMR and ESD in local recurrence rates, positive margins, LNM, complications, or need for surgery despite the limitations of EMR[18,19].

Endoscopic resection is the preference in m1 to m3 adenocarcinomas but this approach is chosen in patients with more favourable factors[20,21]. In sm1 carcinomas, endoscopic resection and oesophagectomy are both considered. The Japan Esophageal Society suggests performing endoscopic resection for m1 and m2 carcinomas. In m3 tumours, surgical, endoscopic or chemo/radiotherapy may be used and the general condition of the patient determines the treatment modality regardless of histopathological type or grade[22].

ESD was developed as an alternative to EMR facilitating en bloc resection and histopathologic assessment[23]. Despite being a more technically challenging procedure, ESD has en bloc resection rates of 83%-100%, complete resection rates of 78%-100%, and local recurrence rates of 0%-2.6% in superficial SCCs, and is now recommended in the European Society of Gastrointestinal Endoscopy guidelines[24]. Consequently, it is the preferred treatment approach in m1 and m2 disease. Tumour morphology is important in selecting patients suitable for ESD. Paris classification of 0-IIa, 0-IIb, and 0-IIc are typically intramucosal and the Japan Esophageal Society have advocated Paris 0-II lesions with m1/m2 invasion and < 2/3 circumferential extent as absolute indications for endoscopic resection. This is due to the low risk of LNM in m1 and m2 tumours along with the previously mentioned morbidity and mortality associated with oesophagectomy.

Endoscopic treatment approaches are associated with some potential complications. Bleeding can occur immediately during the procedure or as a delayed consequence following the procedure. Prophylactic coagulation and prompt identification and treatment are essential for successful outcomes. All ESD knives have haemostatic capabilities. However, the hybrid knives have been shown to reduce the need for haemostatic devices and regular haemostasis compared with conventional knives[25]. Specific haemostatic devices may be necessary in larger vessels. Clips are reserved for uncontrolled bleeding as they may interfere with further dissection. ESD is associated with a higher risk of perforation when compared with EMR and has a reported incidence of 0%-6.9%[26]. Conservative decompression with a nasogastric tube and nutritional support may be required for successful management. Small defects of less than 1cm can be treated with by through the scope clips while defects of up to 2 cm may require over-the-scope clips[27]. Self-expanding metallic stents can also be used as a salvage option. Similarly, strictures are more common following ESD with those having dissection of more than a 75% circumference at higher risk. The treatment of a stricture includes endoscopic balloon dilatation which may be performed in conjunction with local steroid injection or temporal oesophageal stent placement.

Following endoscopic resection, prognosis and further management is based on histologic type, lesion depth, lesion size, lymphovascular or venous invasion and cut margin status. Any case with positive margins should be considered for an oesophagectomy[28]. There is no guidelines of the role of surveillance endoscopy in such cases but a watch and wait approach may be appropriate in patients with several co-morbidities.

CONCLUSION

In conclusion, endoscopic resection is a feasible treatment approach in early oesophageal cancers. Appropriate staging of lesions is crucial for judicious patient selection. ESD is associated with higher rates of en bloc, curative resections and lower recurrence rates compared to EMR. However, EMR is a perfectly viable option in some cases and has fewer complications. Hybrid techniques are being evaluated to combine the advantages of ESD and EMR.