Esophageal cancer (EC) is defined by an uncontrolled growth of tissues in the muscular hollow channel separating the throat from the stomach known as the esophageal wall. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two primary histological forms [1]. While EAC develops from glandular cells and mostly affects the lower esophagus, ESCC begins in the squamous epithelial cells lining the esophagus and primarily affects the upper and middle portions. Esophageal cancer is the seventh most prevalent cancer in terms of incidence and the sixth most common cause of cancer-related deaths globally [2]. According to recent studies, 90% of EC cases globally are caused by ESCC, which is particularly common in areas referred to as the “EC belt”, encompassing sections of China, Iran, and central Asian republics [3]. On the other hand, EAC is more commonly observed in Western industrialized countries [4].

The risk factors for EAC include gastroesophageal reflux disease (GERD) and obesity, which is associated with the development or exacerbation of GERD [5]. Barrett’s esophagus (BE), a condition in which the lining of the lower esophagus undergoes changes (metaplasia), is a strong risk factor for EAC [6]. In contrast, the main known risk factors for ESCC include tobacco smoking, alcohol consumption, consumption of pickled vegetables, hot food and beverages, and poor nutrition [7]. The primary treatment for EC is esophagectomy, or surgical removal of the esophagus. However, it is associated with significant mortality and morbidity rates, and many instances are detected at advanced stages, where surgery alone may not be sufficient [8]. According to recent studies, EGFR may be used as a therapeutic target for EC [9]. Several medicines that hinder EGFR signaling have been developed, providing viable therapeutic options for EC. Biological medicines that target EGFR are being developed as new anticancer treatments [10]. Recently, most clinicians would recommend radical esophagectomy as the preferred treatment. Chemoradiation (CRT) is an alternative treatment, particularly for those who are unable to undergo surgery. In addition, the National Comprehensive Cancer Network recommendations propose ramucirumab, a VEGFR-2 antibody, in combination with paclitaxel, docetaxel, or irinotecan as a second-line treatment for unresectable or metastatic cancer. Interestingly, the KEYNOTE-590 trial will investigate the potential benefit of adding pembrolizumab to 5-FU plus cisplatin in patients with unresectable or metastatic EC [11]. In such circumstances, a multidisciplinary strategy combining surgical and non-surgical treatments is used to establish a cure. Endoscopic treatment is an option for mucosal cancer, but surgery is often suggested for resectable invasive tumors. Finding authorized medications that can be repositioned to treat EC patients is more time- and cost-effective than developing new ones for the treatment of different conditions [12]. Radiation therapy, chemotherapy, targeted medication therapy, and immunotherapy are also suggested depending on the stage and severity of the malignancy [8].

Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are the two most common types of EC. Surgery has typically been the primary treatment for localized SCC and AC of the esophagus, particularly in those with early-stage illness. Surgery is essential in the treatment of resectable EC, particularly adenocarcinoma. Over the last three decades, advances in surgical techniques and radiation procedures have greatly improved clinical outcomes. Despite these major advances, survival rates with surgery alone for locally advanced EC remain low, with a median 5-year overall survival (OS) of only 20% [13]. For the treatment of EC, surgery is still the most effective single-modality therapy. The increased risk of relapse after esophagectomy has motivated researchers to look into multidisciplinary treatment options such as concurrent chemoradiotherapy (CCRT) with or without surgery [14]. However, the best treatment option for EC is still up for debate. Much research evaluating the curative potential of CCRT has cast doubt on the notion that surgery is an unavoidable aspect of curative therapy in the last decade [15].

It is feasible to have surgery to remove EC if it is discovered early and has not spread. The most common treatment for EC is surgery, although the extent of surgery varies greatly from patient to patient [16]. To diagnose remaining cancer cells after surgery, surgical treatment may be complemented with additional modalities such as chemotherapy and radiation therapy. To eradicate cancer cells, the procedure of surgery can be performed alone or along with other treatments.

The surgical approach involves the removal of a portion of the stomach, the segment of the esophagus affected by cancer, and approximately 3 to 4 inches (about 7.6 to 10 cm) of healthy esophagus above it if the cancer is located in the lower part of the esophagus, close to the stomach, or at the gastroesophageal (GE) junction where the esophagus and stomach meet. Afterward, the remaining esophagus is connected to the stomach either high in the chest or in the neck [17].

If the cancer is small, confined to the superficial layers of the esophagus, and has not spread, it can be removed along with the surrounding healthy tissue. This surgical procedure can be performed using an endoscope, which is inserted through the throat and into the esophagus.

For individuals without invasion of surrounding organs or distant metastasis, esophagectomy is considered one of the most effective treatments. Esophagectomy involves the partial or total removal of the esophagus. Surgery may be used to remove the esophagus and any nearby lymph nodes in order to treat the cancer if it has not spread significantly beyond the esophagus [18]. Unfortunately, in most cases, esophageal malignancies are not detected early enough for surgery to be successful. The three most commonly used techniques for thoracic EC are the transhiatal method, Ivor Lewis esophagectomy (right thoracotomy and laparotomy), and the McKeown procedure (right thoracotomy followed by laparotomy and neck incision with cervical anastomosis) [19]. It is worth mentioning that certain studies have shown that patients who undergo whole-piece esophagectomy have significantly higher survival rates compared to those who undergo transhiatal esophagectomy. This suggests that when the tumor is located in the lower esophagus or the cardia, whole-piece esophagectomy is preferred over transhiatal esophagectomy. The choice of surgical approaches and treatment strategies may vary based on the size and location of the tumor [20].

Esophagectomy can be performed using various methods. Regardless of the technique employed, esophagectomy is a complex procedure that often requires a prolonged hospital stay. It is crucial to have experienced professionals with extensive expertise in treating esophageal tumors and performing these operations [21].

The traditional open technique for esophagectomy entails creating one or more significant incisions (cuts) in the neck, chest, or abdomen. The neck and abdomen are where the initial incisions are made during a transhiatal esophagectomy. A transthoracic esophagectomy, on the other hand, necessitates major incisions in the chest and abdomen [22]. In some treatments, the incisions are made in the neck portion as well as in the chest and in the abdomen.

Minimally invasive esophagectomy (MIE), which incorporates several surgical methods aimed at minimizing surgical stress, includes thoracoscopic/laparoscopic esophagectomy. Nowadays, MIE procedures include thoracoscopy/laparotomy, mediastinoscopy/laparoscopy, mediastinoscopy/laparotomy, and robot-assisted surgery with minimal incisions (RAMIE) ^[23][24][23,24]. With developments in endoscopic equipment and technology, surgically performed esophagectomy has grown in popularity [25]. For some early malignancies, multiple small incisions rather than one large one can be used to remove the esophagus. A laparoscope, a small, flexible tube with a light, is inserted through one of the incisions during surgery to provide visual guidance. Subsequently, surgical instruments are introduced through additional small incisions, allowing for precise removal of the esophagus [26]. To achieve successful outcomes with this treatment approach, it is crucial for the surgeon to possess exceptional skill and extensive experience in performing esophageal removal using minimally invasive techniques [27].

The findings indicate that both minimally invasive and open esophagectomy have similar effects on achieving radical tumor treatment [28]. Minimally invasive esophagectomy has demonstrated benefits in reducing intraoperative blood loss, postoperative hospital stays, pain, as well as the risk of pulmonary infection and vocal cord paralysis [29]. Therefore, it deserves clinical promotion and widespread application [30].

Lymph nodes surrounding the esophagus are also removed during this form of esophagectomy. According to a study, a minimum of 15 lymph nodes are usually excised during surgical procedures [31]. The prognosis is less favorable if cancer has spread to the lymph nodes, and the physician might advise additional treatments like chemotherapy or radiation therapy after the procedure.

Surgical resection has been the mainstay treatment for localized EC for several decades. Transhiatal esophagectomy and transthoracic techniques, such as Ivor Lewis esophagectomy (abdominal and right thoracic route, also known as Lewis–Tanner esophagectomy), are surgical options for resecting esophageal carcinoma [32].

Another method is the three-incision modified McKeown esophagectomy [33], which entails a laparotomy, right thoracotomy, and neck anastomosis, or a left thoracotomy or left thoracoabdominal approach [34]. The surgical procedure chosen is determined by the location of the tumor and the physician’s discretion. All of these surgeries are complicated, and treatment at high-volume clinics with experienced surgeons and critical assistance with care has been linked to better results [35].

As with any surgery, there are risks associated with esophageal surgery. Anesthesia reactions, blood clots in the lungs or other areas, infections, and excessive bleeding are examples of short-term complications [36]. After surgery, the majority of people will experience some pain, which can typically be controlled with painkillers. Lung issues are quite common, and the possibility of developing pneumonia can result in a lengthy hospital stay and, in extreme cases, even death. Some individuals may experience changes in their voice following the surgery [37]. There is a chance of a leak forming at the point where the stomach (or intestine) connects to the esophagus, which could necessitate additional surgery to fix. However, due to advancements in surgical techniques, this occurrence is now less common. Some patients may experience swallowing issues due to strictures, which are narrowing conditions that can develop where the esophagus is surgically connected to the stomach [38]. These strictures can be addressed through an upper endoscopy procedure to alleviate the symptom. Surgery can sometimes damage the nerves responsible for stomach contraction, resulting in delayed gastric emptying, leading to regular nausea and vomiting [39]. Additionally, because the ring-shaped muscle (the lower esophageal sphincter) that normally keeps bile and stomach contents within the stomach may be removed or modified during surgery, there is a risk of bile and stomach contents flowing back into the esophagus, resulting in symptoms like heartburn. Antacids and motility medications can sometimes help manage these symptoms, but this surgery’s complications can sometimes be fatal ^[40][41][40,41].

Various treatments are available for managing esophageal obstruction and difficulty swallowing (dysphagia):

If the esophagus has been narrowed due to EC, the surgeon may opt to place a metal tube (stent) to keep the esophagus open. This procedure is performed using an endoscope and specialized tools. Other treatment options include surgery, radiation therapy, chemotherapy, laser therapy, and photodynamic therapy. In cases where swallowing difficulties persist after surgery, a feeding tube may be utilized. This tube allows for direct delivery of nutrition into the stomach or small intestine, enabling the esophagus to heal following cancer treatment [42].

During an esophagogastrectomy, a significant portion of the stomach, as well as the esophagus and adjacent lymph nodes, is removed. The surgical procedure involves removing a portion of the stomach, the cancerous part of the esophagus, and roughly 3 to 4 inches (about 7.6 to 10 cm) of normal esophageal tissue above the tumor if the cancer is in the lower part of the esophagus close to the stomach or at the gastroesophageal (GE) junction [43]. The rest part of the stomach is then raised and reattached to the esophagus. In some cases, a segment of the colon may be utilized for the connection [44].

Esophagectomy is a complex surgical treatment associated with significant rates of morbidity, mortality, and recurrence. The eligibility of a patient for surgical resection depends heavily on the extent of the disease and the patient’s overall health. Accurate clinical staging plays a crucial role in determining the initial treatment plan for EC [45]. This includes a thorough clinical examination and computed tomography (CT) scans of the neck, chest, and abdomen for proper staging. Endoscopic ultrasound (EUS) and 18F fluorodeoxyglucose positron emission tomography-CT (PET-CT) should also be employed to assess the presence of lymphatic or distant metastatic disease in individuals with advanced malignancies who are potential candidates for surgical resection. Subsequently, a multidisciplinary team should determine the most appropriate treatment for each patient, taking into account factors such as tumor stage, location, histological subtype, comorbidities, and age [46].

Endoscopic resection or endoscopic treatment can be used to treat early EC (EEC) that is limited to the mucosa layer and has not spread to lymph nodes (LNM) [47]. Early EC refers to tumors confined to the mucosa or submucosa without lymphatic dissemination or distant metastases. Advancements in endoscopic technology have increased the detection rate of early EC, with 31% of patients being diagnosed at an early stage [48]. Besides detection, endoscopic options have also been utilized for the treatment of an increasing number of early esophageal lesions.

Endoscopic resection (ER) is appropriate for lesions that are limited to the lamina propria or muscularis mucosae. On the other hand, due to the increased risk of lymph node metastases, patients with lymphovascular invasion of the submucosa or muscularis mucosae are not candidates for ER [49]. Endoscopic ablation (radiofrequency ablation, cryoablation, and photodynamic therapy), endoscopic mucosal resection, and endoscopic submucosal dissection are all options for endoscopic resection. Patients may not be eligible for ER if they have certain conditions, including large lesions (greater than 2 cm in size), Barrett’s esophagus, and other esophageal conditions like varices [50]. Patients who are suited for ER need constant supervision for an extended period of time [51]. Esophagectomy may be recommended for patients who are unsuited for ER but are fit medically, while chemotherapy and radiation therapy may be considered for those who are unable to undergo surgery. Even though new research indicates that endoscopic therapy may be a secure substitute for patients with “high-risk” early EC (EEC), esophagectomy is still the advisable treatment for these individuals. In early EC, endoscopy therapy provides viable alternatives to traditional esophagectomy while causing significantly fewer complications. Endoscopic diagnosis and treatment represent the future trend in EC management, facilitated by advancements in endoscopic techniques.

When a patient is referred for endoscopic therapy of early EC, the tumor’s stage and characteristics must first be determined. This is accomplished through a combination of endoscopic examinations and possibly other tumor progression modalities. Before making decisions regarding endoscopic therapy, a thorough examination of the lesion with the assistance of white-light endoscopy is essential. It is necessary to cleanse the esophagus to remove any liquids, food, or debris, followed by a comprehensive examination of the affected areas using white-light endoscopy. According to recent research, high-definition endoscopy surpasses standard-definition endoscopy in assessing mucosal changes in patients with Barrett’s esophagus [52]. While white-light endoscopy remains the best method for assessing resectability, previous studies have explored additional approaches. One such approach is endoscopic ultrasound (EUS), which enables clinicians to determine the depth of the lesion and identify potential locoregional lymph nodes [53].

Curative therapy and palliative therapy are the two general categories of endoscopic management for EC [54]. Curative therapy is typically used for early ECs that are restricted to mucosa and do not involve lymph nodes. When curative therapy is no longer feasible due to disease progression, the focus shifts to palliative care aimed at symptom improvement, particularly dysphagia. Endoscopic management in palliative care entails esophageal stent implantation, debulking, and dilatation [55].

Endoscopic Resection (ER) is the primary method for endoscopic management of early EC. For cases of high-grade dysplasia (HGD) and early EC, various Endoscopic Resection methods have been developed. Endoscopic Mucosal Resection (EMR) or Endoscopic Submucosal Dissection (ESD) are two methods for performing ER [56]. Both adenocarcinomas and squamous cell carcinomas (SCCs) can be treated with ER. According to the TNM staging of tumors (Table 1), the spectrum of conditions in which ER can be conducted in patients with adenocarcinoma often encompasses premalignant low-grade dysplasia in a patient with Barrett’s esophagus (BE) up to, in rare situations, stage T1b adenocarcinoma. SCCs in patients with early EC staged as T1 or intramucosal can be treated with ER.

Currently used EMR methods typically allow for one-piece resection of lesions ranging from 15 to 20 mm. En bloc resection of larger mucosal lesions is possible with ESD. The choice between these methods is determined by the endoscopic equipment and the experience of the specialists. ESD is a promising alternative to EMR for the treatment of HGD and early-stage EC because it allows for endoscopic en bloc excision of lesions larger than 2 cm in diameter.

Several EMR techniques for endoscopic resection can be categorized on the basis of using a suction device or not. EMR is normally carried out using either the ligation- or cap-assisted technique. The cap-assisted technique involves affixing a specially created transparent plastic cap to the end of an endoscope, as first reported by Inoue and Endo [57]. The cap-assisted approach, commonly known as the “suck and cut” method, involves sucking the mucosa into a cap-fitted endoscope and then cutting the mucosa with a snare. Before suctioning, the snare is often opened as part of a pre-assembled kit. An alternative is to use a ligation device, which acts on the same “suck and cut” principles as the cap-assisted technique. This is the most often used approach in the United States. In the ligation-assisted technique, an instrument resembling a variceal band ligator is attached to the upper endoscope, and the mucosa is suctioned before a band is wrapped around it. Afterward, a snare is passed, and the band-supported mucosa is removed. Recent developments include the ability to advance a snare through the working channel of a standard endoscope, along with updated ligation cylinders equipped with multiple rubber bands, enabling endoscopists to perform multiple resections without the need to remove and reintroduce the endoscope [58]. Only small tumors smaller than 20 mm in diameter can be removed and blocked with tumor-free lateral margins, which appears to be the technique’s principal drawback.

Evidence contrasting the two EMR approaches shows that they are, on the whole, comparable. The ligation-assisted method was faster with smaller resection specimens than the cap-assisted method, according to a randomized controlled experiment comparing the two procedures. However, the maximal thickness and adverse event rate of the resection specimens produced by both procedures were similar [59].

The ESD procedure involves dissecting the submucosal layer beneath the carcinoma using an electronic knife to obtain a large resection specimen with the neoplasm resected en bloc. This process involves three steps. First, the tumor is marked with electrocautery, then it is raised by injecting a saline solution beneath it, and finally, it is excised with an electrocautery knife. With the more current ESD approach, the targeted tissue is removed in one piece after carefully dissecting the submucosal lesions [60]. The drawback is that it takes longer and necessitates a deeper resection, which could enhance adverse effects even if it offers an en bloc specimen and can reveal information regarding resection margins [61]. While ESD had higher rates of curative resection and lower local recurrence rates than EMR, these advantages were outweighed by longer procedures and higher rates of bleeding and perforation according to a systematic review and meta-analysis comparing the two techniques [62]. Compared to EMR, some studies show that ESD may be linked to a higher risk of strictures and esophageal perforation [63].

In case of squamous cell carcinoma (SCC), ESD has shown superior outcomes in contrast to the EMR. According to the study’s findings, if the diagnosis is SCC, EMR is typically thought to be suitable for minor lesions (10 mm or smaller); however, it is ideal for patients with bigger lesions to have ESD [64]. For the excision of Barrett’s esophagus (BE) or early esophageal adenocarcinomas, current standards recommend EMR unless the lesions are larger than fifteen mm, do not lift well, or are at risk for submucosal invasion. In such cases, ESD should be performed. While EMR is suitable for smaller lesions, current guidelines typically advise ESD for individuals with squamous cell carcinoma (SCC) [65].

Endoscopic therapy has become a viable option for individuals with neoplasia or early EC due to the low rates of lymphatic or hematogenous spread and the difficulties associated with esophagectomy. These treatments can be divided into two groups depending on whether they are used alone or in conjunction with other methods: ablative and non-ablative [66].

The use of ablative therapy is typically limited to flat lesions. Radiofrequency ablation (RFA) is the most popular type of ablative therapy. Cryoablation and photodynamic therapy (PDT) are other less popular techniques. Ablative therapy’s main goal is to eliminate any precancerous or malignant tissue that may still be present in order to stop recurrence.

Radiofrequency ablation (RFA) is the application of thermal energy directly to the esophageal mucosa. It generates thermal energy by using radiofrequency waves to destroy tissue. This can be performed with an endoscope-mounted device for more focused ablation or a circumferential ablation catheter. The delivered energy ensures uniform treatment to a depth of approximately 500 μm. As a consequence, the risk of stenosis is decreased because the treatment does not penetrate the submucosal layer [67].

RFA is typically advised for patients with intra-mucosal cancer, dysplasia, or non-nodular lesions, according to current recommendations. In patients who have undergone endoscopic resection (ER), it should be performed to treat any remaining Barrett’s esophagus (BE). RFA’s effectiveness in treating patients with BE or adenocarcinoma has grown, but its application to the treatment of squamous cell carcinoma (SCC) is still being explored. Recent research on early SCC has yielded encouraging results, with high rates of total eradication and low recurrence rates [68]. RFA is typically the most popular technique, and there is growing evidence to support its usefulness as well as a solid safety track record.

PDT is an ablative procedure that causes mucosal destruction by activating a photosensitizer drug with laser light. PDT has been shown to be effective in the treatment of both esophageal adenocarcinomas and SCC [69]. PDT has received the most research attention of any ablative technique developed for the treatment of dysplasia and early EC. Intravenously or orally, a photosensitizing agent that is selectively absorbed by fast-growing cells, such as cancer cells, is administered. The photosensitizer is activated by applying an endoscopic laser directly to the malignant tumor [70]. But its serious side effects such as prolonged cutaneous photosensitivity, stricture formation, and recurrence have limited its use.

Cryoablation has been considered for the treatment of pre-malignant and malignant esophageal problems [71]. Application of liquid nitrogen therapy is most frequently used. Using an open-tipped catheter, freezing carbon dioxide or liquid nitrogen is sprayed directly onto the tumor [72]. The targeted tissue is “frozen” and then thawed. This “freeze and thaw” cycle is repeated until the lesion is destroyed [73].

Endoscopic therapy is essential for treating both pre-malignant alterations and early-stage EC patients who have a low risk of lymph node metastases. Endoscopic technology’s rapid advancement has improved current diagnostic and therapeutic capabilities for early EC. Endoscopic therapy has a lower morbidity and mortality rate than surgery, as well as equal rates of cure, rates of survival during five years, and a higher standard of living. In particular, post-operative complications from the treatment of EC can be managed with it. These fantastic outcomes are limited by the requirement for many treatments to achieve total eradication and the possibility of recurrences after eradication. Treatment success depends on patient compliance and careful patient selection using a multidisciplinary approach.