GMKA
Support

Esophageal Cancer: symptoms, staging and treatment

Oncology

Authors

Expert image
Yoshiko Iwai, MD
Author
Expert image
Jason M. Long, MD, MPH
Author
Read in Ukrainian

Introduction

Esophageal cancer is the seventh most common cancer among men and the 13th most common cancer among women, making it the eighth most commonly diagnosed cancer worldwide [1]. In 2020, more than 600,000 cases were diagnosed in the world[1].
While many people who are diagnosed with esophageal cancer will eventually die from the disease, advancements in treatment have improved survival rates over recent decades. In the 1960s and 1970s, esophageal cancer resulted in an approximate 5% survival rate five years after diagnosis; these rates have increased to approximately 20% survival at five years in 2022 [2]. Despite improvements in mortality, esophageal cancer remains a challenging solid tumor due to its modest response to chemoradiation and surgical complexity.
The two main types of esophageal cancer are squamous cell carcinoma and adenocarcinoma. Rarely, lymphoma, melanoma, or sarcomas may originate in the esophagus. This chapter will focus on the two most common types.

Symptoms

Most people are diagnosed with esophageal cancer due to their symptoms, which often present at later stages of disease. A 2016 Surveillance, Epidemiology, and End Results (SEER) registry study reported that the majority of individuals presented with distant disease (cancer had metastasized) compared to regional (spread to nearby lymph nodes) or localized (restricted to the primary site) disease. However, the proportion of individuals presenting with localized disease progressively increased from 1973 to 2009 [3].
Common symptoms of esophageal cancer include dysphagia, hoarseness, chronic cough, chest pain, weight loss, and vomiting. When esophageal cancer metastasizes, the most common location is the liver, followed by distant lymph nodes, lung, bone, and brain [4]. Symptoms associated with metastatic disease vary by metastatic site but may include abdominal pain, jaundice, or nausea for liver metastases and limb or back pain for bone metastasis. Many of these symptoms are nonspecific and may occur in different disease processes; thus, a high index of suspicion and low threshold for imaging is often required by treating physicians.

Screening

There are no formal screening recommendations for esophageal cancer provided by the United States Preventive Services Taskforce for the general population. However, certain hereditary conditions increase esophageal cancer risk and warrant special attention. For tylosis with non-epidermolytic palmoplantar keratosis and Howel-Evans syndrome (RHBDF2 gene), family members should receive screening upper gastrointestinal endoscopy after the age of 20. For individuals with a diagnosis of Bloom syndrome (BLM/RECQL3 gene), screening for GERD with or without endoscopy may be considered after the age of 20. For individuals with a diagnosis of Fanconi anemia (FANCD1, BRCA2, FANCN/PALB2), esophageal endoscopy may be considered for general screening [5].
For individuals with familial Barrett’s esophagus (no candidate genes identified to date), screening upper gastrointestinal endoscopy is recommended after the age of 40, especially if the individual has a history of GERD. For non-familial cases, Barrett’s esophagus remains the only known precursor to esophageal adenocarcinoma [6]. Screening in non-familial Barrett’s esophagus is therefore recommended via endoscopic screening for metaplastic and dysplastic changes for individuals with risk factors, including age above 50, chronic GERD, central obesity, being male or white, and history of hiatal hernia [6].

Evaluation

Esophageal cancer is typically diagnosed with esophagogastroscopy and tissue biopsy. Esophagogastroscopy or esophagogastroduodenoscopy (EGD) is essential for assessing tumor size, location, and proximity to the gastroesophageal junction and upper esophageal sphincter [7].
Tumor location is categorized as upper (18 to 24 cm), middle (24 to 32 cm), or lower (32 to 40 cm) with respect to the upper incisors as measured using an EGD. Computed tomography (CT) scan of the chest and abdomen using intravenous and oral contrast are also critical for assessing potential invasion of the tumor into surrounding structures and vasculature. If endoscopy is not available, cross-sectional imaging such as CT scan can be used to determine tumor location but is not as sensitive as ultrasound to determine extent of esophageal wall invasion. Magnetic resonance imaging (MRI) is recommended if there is concern of aortic invasion.  Positron emission tomography (PET/CT) is an essential component of esophageal cancer staging and is used to evaluate for metastatic spread to regional and distant lymph nodes as well as spread to distant organs such as liver, bone, and lungs.
Endoscopic ultrasonography (EUS) can visualize the esophageal wall, providing information on tumor depth and lymph node status via biopsy [7]. EUS is particularly useful for characterizing invasion into the various layers of the esophageal wall which can differentiate between T stages. Tumor will appear hypoechoic (dark) with gradual loss of the normal esophageal layered pattern [5]. Similarly, mediastinal and perigastric lymph nodes with malignant invasion or inflammatory response will appear hypoechoic (dark), enlarged, homogeneous, and well-circumscribed. Fine needle aspiration (FNA) of suspicious lymph nodes is recommended if they can be performed without crossing primary tumor or major vasculature. For superficial tumors, EUS has been associated with inaccurate determination of T-staging [8].
Recent literature on superficial squamous cell carcinoma of the esophagus demonstrated that using EUS after conventional endoscopic methods was not associated with increased diagnostic accuracy [9]. Therefore, endomucosal resection (EMR) or endoscopic submucosal dissection (ESD) is recommended for staging superficial tumors and nodular tumors smaller than 2 cm and is therapeutic for T1a tumors, especially with adjunctive ablation therapy [5,10–12]. Pathologic evaluation of the margin would determine whether the EMR or ESD was completely curative or additional resection is needed. For large, obstructing tumors, performing EUS may increase risk of perforation. Wire-guided or mini EUS probes can bypass the obstruction in some cases [5]. Dilation of the malignant stricture may be permissible with the understanding of increased perforation risk thereafter [5].
Tissue biopsy, completed during endoscopy, is necessary for determining cell type and accurate clinical staging. Six to eight biopsies should be performed with standard endoscopy forceps for satisfactory tissue collection for histologic evaluation [5]. Esophageal cancers are typically classified as squamous cell carcinoma or adenocarcinoma by characteristic features on histologic examination. In cases where histologic distinction is challenging, additional markers may be used for diagnostic clarity. These include p63, p40, and cytokeratin 5/6 for squamous etiologies and presence of intracellular mucin on Alcian blue-PAS staining for adenocarcinoma [10].

Staging

Esophageal cancer is staged with the American Joint Committee on Cancer (AJCC) staging manual. The recent release of the eighth edition includes data from the Worldwide Esophageal Cancer Collaboration. Staging criteria take into consideration anatomic characteristics of the tumor (T), nodal involvement (N), and metastasis (M) (Table 1).
Table 1. Esophageal and Esophagogastric junction tumor stages
The primary tumor (T) stage is classified by degree of tumor invasion. It ranges from T0 to T4, beginning with no evidence of primary tumor, through the lamina propria, muscularis mucosae, submucosa, muscularis propria, adventitia, adjacent structures, and more distant structures (T4) (Figure 1).
Figure 1. Illustration of esophageal cancer depth of invasion
The regional lymph node involvement (N) stage is determined by the number of lymph nodes involved, categorized as: no nodal involvement, 1-2 nodes, 3-6 nodes, and 7 or more nodes (N0 to N3). Metastasis (M) is determined as having distant disease or not (M0, M1). Clinical and pathologic staging groups are separately characterized for esophageal squamous cell carcinoma (Table 2, 3) and adenocarcinoma (Table 4, 5).
Table 2. Squamous Cell Carcinoma Clinical Stage Groups
StageTumor (cT)Node (cN)Metastasis (M)
0TisN0M0
IT1N0-1M0
IIT2N0-1M0
IIT3N0M0
IIIT3N1M0
IIIT1-3N2M0
IVAT4N0-2M0
IVAAny TN3M0
IVBAny TAny NM1
Table 3. Squamous Cell Carcinoma Pathological Stage Groups
StageTumor (pT)Node (pN)Metastasis (M)Grade (G)Location
0TisN0M0N/AAny
IAT1aN0M0GX, G1Any
IBT1aN0M0G2-3Any
IBT1bN0M0GX, G1-3Any
IBT2N0M0G1Any
IIAT2N0M0GX, G2-3Any
IIAT3N0M0AnyLower
IIAT3N0M0G1Upper/middle
IIBT3N0M0G2-3Upper/middle
IIBT3N0M0GXAny
IIBT3N0M0AnyUnknown location
IIBT1N1M0AnyAny
IIIAT1N2M0AnyAny
IIIAT2N1M0AnyAny
IIIBT2N2M0AnyAny
IIIBT3N1-2M0AnyAny
IIIBT4aN0-1M0AnyAny
IVAT4aN2M0AnyAny
IVAT4bN0-2M0AnyAny
IVAAny TN3M0AnyAny
IVBAny TAny NM1AnyAny
Table 4. Adenocarcinoma Clinical Stage Groups
StageTumor (cT)Node (cN)Metastasis (M)
0TisN0M0
IT1N0M0
IIAT1N1M0
IIBT2N0M0
IIIT2N1M0
IIIT3, T4aN0-1M0
IVAT1-4aN2M0
IVAT4bN0-2M0
IVAAny TN3M0
IVBAny TAny NM1
Table 5. Adenocarcinoma Pathological Stage Groups
StageTumor (pT)Node (pN)Metastasis (M)Grade (G)
0TisN0M0N/A
IAT1aN0M0GX, G1
IBT1aN0M0G2
IBT1bN0M0GX, G1-3
ICT1N0M0G3
ICT2N0M0G1-2
IIAT2N0M0GX, G3
IIBT1N1M0Any
IIBT3N0M0Any
IIIAT1N2M0Any
IIIAT2N1M0Any
IIIBT2N2M0Any
IIIBT3N1-2M0Any
IIIBT4aN0-1M0Any
IVAT4aN2M0Any
IVAT4bN0-2M0Any
IVAAny TN3M0Any
IVBAny TAny NM1Any
In the preoperative phase, a clinical stage or cTNM stage is assigned to each patient. The eighth edition of the AJCC manual recommends two strategies for establishing cTNM stage:
(1) EGD with biopsy, EMR/ESD, EUS, and EUS-fine needle aspiration (FNA), followed by PET or CT scan;
or (2) CT or PET evaluation, then pursuing clinical staging.
The first approach is costly but allows for all staging information to be gathered in one sitting endoscopically. The second approach is less costly, where metastatic disease would not require any additional testing, but takes more time and coordination of care to achieve a diagnosis. In the postoperative phase, pathologic staging or pTNM stage is assigned using final surgical pathology. Notably, use of neoadjuvant therapy may downstage clinical staging.

Treatment

Esophageal cancer is approached with multimodal management. For nonmetastatic disease, complete resection of the primary tumor remains the gold standard for treatment with curative intent. Superficial T1aN0 tumors can be treated with EMR followed by ablation whereas T1bN0 tumors are treated with esophagectomy [11].  T2N0 tumors are also most commonly treated with upfront esophagectomy (this is debatable), whereas more locally advanced disease, T3-T4a disease  and/or any nodal involvement, is best treated with neoadjuvant chemoradiotherapy followed by esophagectomy if re-staging reveals good response with no signs of metastatic disease. T4b disease and/or extensive nodal involvement in multiple cavities precludes surgical resection and should instead be treated with definitive chemoradiation followed by immunotherapy. In the preoperative planning phase, it is essential to evaluate the resectability of the tumor using the imaging and diagnostic procedures listed above.
In the neoadjuvant setting, systemic therapy is recommended for patients with locally advanced esophageal adenocarcinoma and squamous cell carcinoma. Chemotherapy choice is determined based on an individual’s performance status [12] and comorbidities. Regimens with two cytotoxic drugs are generally recommended due to lower toxicity, while three cytotoxic drug regimens are reserved for patients with high performance status. The ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial, a multicenter phase III randomized controlled trial, demonstrated significant improvements in overall survival and disease-free survival in patients with T2-T3, N0-N1, M0 disease and patients with esophagogastric junctional tumors who received paclitaxel and carboplatin before surgery [14]. They included both squamous and adenocarcinoma in their trial and contributed to the recommendations for current chemotherapy regimens.
Preferred regimens for preoperative chemoradiation include:
  1. Paclitaxel 50 mg/m2 IV on Day 1, Carboplatin AUC 2 IV on Day 1, weekly for five weeks;
  2. Oxaliplatin 85 mg/m2 IV on Days 1, 15, and 29 for three doses, Capecitabine 625 mg/m2 PO BID on Days 1–5 weekly for five weeks.
Preferred regimens for postoperative chemoradiation include:
  1. Nivolumab 240 mg IV every 14 days for 16 weeks, followed by Nivolumab 480 mg every 28 days, maximum treatment duration of 1 year;
  2. Capecitabine 1000 mg/m2 PO BID on Days 1–14, Oxaliplatin 130 mg/m2 IV on Day 1, cycled every 21 days.
For metastatic or locally advanced cancer where local treatment is no longer warranted, first-line therapies include:
  1. Trastuzumab 8 mg/kg IV loading dose on Day 1 of cycle 1, then Trastuzumab 6 mg/kg IV every 21 days;
  2. Trastuzumab 6 mg/kg IV loading dose on Day 1 of cycle 1, then 4 mg/kg IV every 14 days;
  3. Oxaliplatin 85 mg/m2 IV on Day 1, Leucovorin 400 mg/m2 IV on Day 1, Fluorouracil 400 mg/m2 IV Push on Day 1, Fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours daily on Days 1 and 2, cycled every 14 days [5].
Targeted biologics and immunotherapy are a new and expanding treatment modality for esophageal cancer, particularly in metastatic disease. Recent data suggest that HER2 amplification is implicated in over 30% of esophageal adenocarcinoma, and the addition of Trastuzumab to chemotherapy has become first-line in the treatment of HER2 amplified esophageal adenocarcinoma [5,15].
The implication of the VEGF pathway has also led to approval of Ramucirumab (VEGFR-2 antibody) for patients with advanced or metastatic gastric or esophagogastric junction (EGJ) adenocarcinoma, as demonstrated by the survival benefits in the REGARD trial [5,15,16]. Immunotherapies with approval include Nivolumab (monoclonal PD-L1 antibody), Pembrolizumab (PD-L1 antibody), and Dostarlimab-gxly (anti-PD-1 antibody) based on Next Generation Sequencing, and select TRK inhibitors, Entrectinib and Larotrectinib, based on NTRK gene fusions [5]. The optimum neoadjuvant regimen including the use of immunotherapy and the adjuvant use of immunotherapy after surgery are areas of active discourse [17].
For patients requiring radiation, multidisciplinary discussion and planning are required for optimal results. Appropriate simulation and 3D conformal planning should be performed before initiation of treatment to minimize unnecessary exposure, including vital surrounding structures. Preoperative radiotherapy dose recommendations are 41.4–50.4 Gy (1.8–2.0 Gy/day) (total 23–28 fractions), postoperative radiotherapy dose recommendations are 45–50.4 Gy (1.8–2.0 Gy/day) (total 25–28 fractions), and definitive radiotherapy dose recommendations are 50–50.4 Gy (1.8–2.0 Gy/day) (total 25–28 fractions).
While esophagectomy is performed with the goal of achieving proximal, distal, and circumferential negative margins, there is minimal consensus on specific surgical approach. Currently, the factors that determine the approach to surgical resection include tumor location, conduit options, patient preference, as well as surgeon experience.
Acceptable operative approaches for resecting esophageal, and esophagogastric junction tumors include Ivor Lewis esophagogastrectomy (laparotomy, right thoracotomy), McKeown esophagogastrectomy (right thoracotomy, laparotomy, with cervical anastomosis), minimally invasive Ivor Lewis esophagogastrectomy (laparoscopy, right thoracoscopy) [18-19], minimally invasive McKeown esophagogastrectomy (right thoracoscopy, limited laparotomy or laparoscopy, with cervical anastomosis), transhiatal esophagogastrectomy (laparotomy with cervical anastomosis), robotic minimally invasive esophagogastrectomy, and left transthoracic or thoracoabdominal approaches with anastomosis in chest or neck. Most surgeons target a 5 to 8 cm proximal margin [20] and 5 cm distal margin [21] to optimize the chances of achieving tumor-free longitudinal margins.
Intraoperative pathological evaluation, including frozen sections of the resected specimen, is recommended for proximal margins. Distal gastric margins may also be considered if there is a concern for residual microscopic disease or disease extending below the gastroesophageal junction. Surgical resection should be expanded if margins return positive, and for distal gastric margin positivity, a total gastrectomy or alternate conduit should be considered. Circumferential margins cannot be effectively evaluated intraoperatively; thus, generous margins are generally pursued with careful attention to avoid skeletonization of the esophagus. From a technical perspective, if local invasion is observed involving the diaphragm, pericardium, or thoracic duct, en bloc surgical resection should be performed with the goal of achieving negative margins. If the tumor is fixed to structures such as the aorta, airway, or prevertebral fascia, the resection should be aborted.
Radical lymph node dissection is recommended regardless of disease stage, surgical approach, or receipt of neoadjuvant therapy. This includes removal of periesophageal, mediastinal, and celiac axis lymphatic tissue. With one randomized control trial [22] performed by Hulscher et al. and few retrospective cohort studies [23,24] assessing lymphadenectomy methods, there is still no consensus regarding the optimal surgical approach. Recent AJCC guidelines recommend resecting ten regional lymph nodes for pT1, 20 nodes for pT2, and 30 or more nodes for pT3 [10]. A 2019 meta-analysis by van Hillegersberg et al. reported significant improvement in survival in esophagectomies with high lymph node yield regardless of neoadjuvant therapy receipt [25]. Based on these data, the 2022 National Comprehensive Cancer Network (NCCN) guidelines recommend resecting a minimum of 15 lymph nodes for all patients undergoing esophagectomy without induction chemotherapy [5].
Data and recommendations are less robust around gastrointestinal reconstruction and the use of alternative conduits. Acceptable sources include a gastric conduit, which is the first preference according to NCCN guidelines, followed by the use of colon or jejunum [5]. There is no strong evidence supporting specific gastric conduit width. Few studies have evaluated rates of anastomotic leak from esophagogastric anastomoses related to conduit width, and reports range from no difference across groups to favoring one over the other [26-28].
A 2017 meta-analysis by Zhang et al. reported no significant difference in rates of anastomotic leak, anastomotic stenosis, delayed gastric emptying, or pneumonia between whole-stomach versus gastric conduit approaches [29]. Evidence is limited for use of narrow conduits <4 cm, and thus whole-stomach gastric conduit or wide tubularized conduit of 4 to 5 cm are generally preferred. Rates of mortality and morbidity for colonic versus jejunal conduits in the literature are variable [30].
Proponents of colonic conduits recommend it for its length and resistance to acid and reflux [31]; however, these conduits can lengthen and dilate with time resulting in redundancy. They can also cause diarrhea in patients due to decreased absorptive capacity [32]. Proponents of jejunal conduits recommend it for its reliable vascular supply, which can be further enhanced by “supercharging” [33], lower likelihood of diarrhea or malabsorption due to redundant native tissue, and intrinsic peristaltic function [30]. Disadvantages of using the jejunum include potential inadequate length, fatty mesentery prohibiting mobility and restricting length intraoperatively, and increased operating time due to a microvascular component. With appropriate preoperative planning and surgeon experience, using either colonic or jejunal conduits can yield excellent results.
Several potential post-esophagectomy complications warrant close and attentive post-operative monitoring and management. The most dreaded complications can include anastomotic leak, conduit necrosis, and chylothorax. Anastomotic leak, typically resulting from ischemia at the site of the new anastomosis, require early recognition to minimize risk of morbidity and mortality [34]. Clinical manifestations of anastomotic leak can vary, depending on a cervical location versus an intra-thoracic location. A cervical anastomotic leak can present with foul smelling drainage and discharge leaking from the cervical incision, new onset atrial fibrillation, tachycardia, congested upper airway with copious airway secretions, elevated WBC and fever. If leakage drains into the mediastinum, the presentation can appear similar to an intrathoracic leak and can include mediastinitis and sepsis.  Intrathoracic anastomotic leak can appear as turbid and/or bilious chest tube drainage, sepsis, new onset atrial fibrillation, tachycardia, changes to respiratory status or mentation, and pain [34].
Imaging studies, such as CT with oral contrast using a barium swallow, can identify location of leak when suspected. Minor anastomotic leaks can be managed with observation, antibiotics, nasogastric decompression, and nutritional therapy as needed, but larger leaks may require operative intervention and vary according to the site of the leak. For cervical anastomotic leak, operative drainage of the neck incision with packing and/or placement of drains is indicated. For intrathoracic anastomotic leak, esophageal stent placement can be considered if there is little to no contamination and the leak is small (<1/4 circumference of the lumen with no areas of necrosis) whereas thoracotomy with operative drainage of the chest and primary repair of the leak with muscle flap buttress is indicated for larger leaks and mediastinal/pleural space contamination [35]. Conduit necrosis can result in significant leak, as well as acute clinical decompensation including sepsis, typically within the first 48 hours after surgery [36]. Given the high risk of mortality with this complication, after immediate resuscitation, these patients should be taken to the operating room for endoscopy and resection of the necrotic conduit and left in discontinuity.
Management of chyle leak is dependent upon amount of drainage: low (<250-500 mL per 24-hour period) versus high (>500 mL per 24-hour period). Low output chyle leak can typically be managed conservatively with drainage, octreotide to decrease chyle flow, and nutritional support, including high-protein, low-fat diet with medium-chain fatty acids, and avoiding long-chain fatty acids. It is important to note that in the early post-operative period where patients have had limited oral intake, chyle leaks may appear clear, as opposed to their typical milky appearance [34]. If patients have high output chylothorax or do not respond to conservative management, local interventions may be warranted. While most patients are initially treated conservatively, conservative management of chylothorax has been reported to fail in approximately 50% of cases [37].
Thoracic duct embolization, disruption, or surgical interventions including ligation, reconstruction, or glue closure, with or without pleurodesis, are preferred therapies for addressing chyle leak. Determination of the appropriate intervention depends on the etiology of the chyle leak, rate of chyle loss, location of leak, patient preference, and risk of operating. It is important to stress that high-output leaks should be addressed early as ongoing losses can result in leukopenia, malnutrition, sepsis, and mortality.

Surveillance

While surveillance remains an integral part of oncologic care after successful therapy for esophageal cancer, there is minimal consensus and no standardized algorithm for surveillance planning. Surveillance is largely determined by the availability of resources, patient and provider preferences, and careful risk-benefit discussions among stakeholders. Notably, 75-90% of esophageal cancers are cited to recur in the first two years after local therapy; however, some recurrences after five years post-local therapy may still have actionable potential [5,38]. NCCN guidelines are summarized here.
For T1a tumors treated with endoscopic resection, EGD is recommended every three months for the first year, every 4-6 months (6 months acceptable for T1a) in the second year, and then annually indefinitely. T1a does not require imaging, while T1b may undergo CT chest and abdomen with contrast every 12 months for three years and then determined based on clinical assessment afterward. For T1b tumors of any nodal stage treated with esophagectomy, CT chest, and abdomen with contrast is recommended every 12 months for three years with EGD as needed. For T1b tumors treated with chemoradiation, EGD is recommended every 3-6 months for two years and then annually for three additional years. CT chest and abdomen with contrast may be considered every 6-9 months for the first two years, then every 12 months for the subsequent five years.
For T2-T4, N0-N+, and T4b tumors treated with bimodal therapy, CT chest and abdomen with contrast is recommended every six months for up to two years if the patient will likely tolerate additional curative therapy for potential recurrence. EGD is recommended every 3-6 months for the first two years, every six months for the third year, and as needed after year 3. For T2-T4, N0-N+, and T4b tumors treated with trimodal therapy, CT chest and abdomen with contrast is recommended every six months for up to two years if the patient will likely tolerate additional curative therapy. EGD is recommended only as needed. The role of carcinoembryonic antigen (CEA) and other tumor markers for the surveillance of esophageal cancers remains largely unknown, and there is no strong evidence supporting regular use.

Controversies

Much debate remains around the role of neoadjuvant chemoradiotherapy prior to surgical resection in cT2N0 disease due to lack of large randomized control trials and inconsistencies in pre-operative staging [39]. A recent retrospective cohort analysis of the United States’ National Cancer Database (NCDB) reported patient, treatment center, and tumor-related factors associated with use of induction therapy for cT2N0 esophageal cancers, and ultimately concluded that induction therapy was not associated with a survival benefit [40]. While these findings align with some prior NCDB studies similarly reporting no significant survival benefit of induction therapy [41], other NCDB studies have reported improved long-term survival with neoadjuvant chemoradiotherapy prior to surgery [42.43]. Current guidelines continue to include the use of neoadjuvant chemoradiotherapy for cT2N0 tumors, but some patients may safely forego neoadjuvant therapy in the future. Recommendations will likely remain conflicted without robust randomized data [44].
The evolution and expansive uptake of minimally invasive esophagectomy (MIE) and robot-assisted MIE (RAMIE) is another area of discussion [45]. While MIE has been shown to improve perioperative results with comparable rates of survival to open esophagectomy, rates of reoperation have reported to be higher and the learning curve is steep [45]. RAMIE has emerged as a surgical technique that may address some of the shortcomings of thoracoscopic-assisted MIE [46]. Literature on RAMIE is still in its infancy and remains sparse. Early findings demonstrate comparable short-term outcomes and shorter ICU stay in RAMIE compared to MIE groups [47,48]. Further studies are warranted to evaluate the short and long-term implications of RAMIE compared to MIE and open esophagectomy, including the learning curve in adopting RAMIE among surgeons.

Summary and recommendations

  • Esophageal cancer is the eighth cause of cancer-related death globally.
  • There are no formal recommendations for esophageal cancer screening. Most patients with esophageal cancer seek medical attention due to symptoms, such as dysphagia, nausea, chest pain, and weight loss, and often present with later-stage disease.
  • Esophageal cancer is staged using a TNM classification system. Clinical staging is critical for preoperative treatment planning. Diagnosis and clinical staging for esophageal cancer are typically made with esophagogastroscopy or EGD and tissue biopsy. EUS is helpful for visualizing tumor depth, thus facilitating accurate clinical staging. For superficial tumors, endomucosal resection or endoscopic submucosal dissection is recommended with the potential of providing curative therapy simultaneously.
  • For resectable tumors (T1a, T1-T3, and T4a), the mainstay of therapy is complete resection of the primary tumor. Locally advanced tumors benefit from neoadjuvant chemoradiation. For nonresectable tumors (T4b, multi-station and/or bulky lymphadenopathy, supraclavicular lymph node invasion, esophagogastric junction involvement, distant metastasis), systemic therapy is the mainstay of therapy.
  • Radical lymph node dissection is recommended regardless of disease stage, surgical approach, or receipt of neoadjuvant therapy. AJCC guidelines recommend resecting ten regional lymph nodes for pT1, 20 for pT2, and 30 or more for pT3. The 2022 NCCN guidelines recommend resecting a minimum of 15 lymph nodes for all patients undergoing esophagectomy without induction chemotherapy.
  • There is no formal surveillance algorithm for esophageal cancer, and surveillance recommendations vary by stage and therapy. Surveillance following esophagectomy commonly includes EGD and imaging, such as CT chest and abdomen with contrast, in the months and years following primary resection. Additional studies are determined based on patient symptoms.

References

  1. Oesophageal cancer statistics [Internet]. World Cancer Research Fund International; 2022 [cited 2022 Jul 15]. Available from: https://www.wcrf.org/cancer-trends/oesophageal-cancer-statistics/
  2. American Cancer Society. Key Statistics for Esophageal Cancer [Internet]. 2022 [cited 2022 Jul 16]. Available from: https://www.cancer.org/cancer/esophagus-cancer/about/key-statistics.html
  3. Basile Njei, McCarty TR, Birk JW. Trends in esophageal cancer survival in United States adults from 1973 to 2009: A SEER database analysis. J Gastroenterol Hepatol. 2016;31(6):1141–6.
  4. Wu SG, Zhang WW, Sun JY, Li FY, Lin Q, He ZY. Patterns of Distant Metastasis Between Histological Types in Esophageal Cancer. Front Oncol. 2018;8:302.
  5. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Esophageal and Esophagogastric Junction Cancers [Internet]. 2022 [cited 2022 Jul 16]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf
  6. Kamboj AK, Katzka DA, Iyer PG. Endoscopic Screening for Barrett’s Esophagus and Esophageal Adenocarcinoma: Rationale, Candidates, and Challenges. Gastrointest Endosc Clin N Am. 2021;31(1):27–41.
  7. American College of Surgeons, Alliance for clinical Trials in Oncology. Esophagus. In: Operative Standards for Cancer Surgery: Thyroid, Gastric, Rectum, Esophagus, Melanoma. Wolters Kluwer; 2019.
  8. Bergeron EJ, Lin J, Chang AC, Orringer AC, Reddy RM. Endoscopic ultrasound is inadequate to determine which T1/T2 esophageal tumors are candidates for endoluminal therapies. J Thorac Cardiovasc Surg. 2014;147(2):765–71.
  9. Ishihara R, Mizusawa J, Kushima R. Assessment of the Diagnostic Performance of Endoscopic Ultrasonography After Conventional Endoscopy for the Evaluation of Esophageal Squamous Cell Carcinoma Invasion Depth. JAMA Netw Open. 2021;4(9):e2125317.
  10. Rice TW, Patil DT, Blackstone EH. 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice. Ann Cardiothorac Surg. 2017;6(2):119–30.
  11. Schlottmann F, Patti MG, Shaheen NJ. Endoscopic Treatment of High-Grade Dysplasia and Early Esophageal Cancer. World J Surg. 2017;41(7):1705–11.
  12. Ramay FH, Vareedayah AA, Visrodia K, Iyer PG, Wang KK, Eluri S, et al. What Constitutes Optimal Management of T1N0 Esophageal Adenocarcinoma? Ann Surg Onc. 2019;26(3):714–31.
  13. West H, Jin JO. Performance Status in Patients With Cancer. JAMA Oncol. 2015;1(7):998.
  14. Shapiro J, Van Lanschot JJB, Hulshof MC, Van Hagen P, Van Berge Henegouwen MI, Wijnhoven BP, et al. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015;1090–1098(16):9.
  15. Turgeman I, Ben-Aharon I. Evolving treatment paradigms in esophageal cancer. Ann Transl Med. 2021;9(10):903.
  16. Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31–9.
  17. Patel MA, Kratz JD, Lubner SJ, Loconte NK, Uboha NV. Esophagogastric Cancers: Integrating Immunotherapy Therapy Into Current Practice. J Clin Oncol. 2022;JCO2102500.
  18. Levy RM, Wizorek J, Shende M, Luketich JD. Laparoscopic and thoracoscopic esophagectomy. Adv Surg. 2010;44:101–16.
  19. Minimally invasive esophagectomy for cancer. Eur J Cardiothorac Surg. 2009;35(1):13–20.
  20. Migliore M, Rassl D, Criscione A. Longitudinal and circumferential resection margin in adenocarcinoma of distal esophagus and cardia. Future Oncol. 2014;10(5):891–901.
  21. Casson AG, Darnton J, Subramanian S, Hiller L. What is the optimal distal resection margin for esophageal carcinoma? Ann Thorac Surg. 2000;69(1):205–9.
  22. Hulscher JB, van Sandick JW, de Boer AGEM. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med. 347(21):1662–9.
  23. Orringer MB, Marshall B, Chang AC, Lee J, Pickens A, Lau CL. Two thousand transhiatal esophagectomies: changing trends, lessons learned. Ann Surg. 2007;246(3):363–72.
  24. Altorki N, Kent M, Ferrara C, Port J. Three-field lymph node dissection for squamous cell and adenocarcinoma of the esophagus. Ann Surg. 2002;236(2):177–83.
  25. Visser E, Markar SR, Ruurda JP, Hanna GB, van Hillegersberg R. Prognostic Value of Lymph Node Yield on Overall Survival in Esophageal Cancer Patients: A Systematic Review and Meta-analysis. Ann Surg. 2019;269(2):261–8.
  26. Tabira Y, Sakaguchi T, Kuhara H, Teshima K, Tanaka M, Kawasuji M. The width of a gastric tube has no impact on outcome after esophagectomy. Am J Surg. 2004;187(3):417–21.
  27. Shu YS, Sun C, Shi W, Lu SC, Wang K. Tubular stomach or whole stomach for esophagectomy through cervico-thoraco-abdominal approach: a comparative clinical study on anastomotic leakage. Ir J Med Sci. 2013;182(3):477–80.
  28. Shen Y, Wang H, Feng M, Tan L, Wang Q. The effect of narrowed gastric conduits on anastomotic leakage following minimally invasive oesophagectomy. Interact Cardiovasc Thorac Surg. 2014;19(2):263–8.
  29. Zhang W, Yu D, Peng J, Xu J, Wei Y. Gastric-tube versus whole-stomach esophagectomy for esophageal cancer: A systematic review and meta-analysis. PLoS One. 2017;12(3):e0173416.
  30. Bakshi A, Sugarbaker DJ, Burt BM. Alternative conduits for esophageal replacement. Ann Cardiothorac Surg. 2017;6(2):137–43.
  31. Yasuda T, Shiozaki H. Esophageal reconstruction with colon tissue. Surg Today. 2011;41(6):745–53.
  32. Strauss DC, Forshaw MJ, Tandon RC, Mason RC. Surgical management of colonic redundancy following esophageal replacement. Esophagus. 2008;21(3):E1-5.
  33. Swisher SG, Hofstetter WL, Miller MJ. The supercharged microvascular jejunal interposition. Semin Thorac Cardiovasc Surg. 2007;19(1):56–65.
  34. Yeung JC. Management of Complications After Esophagectomy. Thorac Surg Clin. 2020;30(3):359–66.
  35. Schaheen L, Blackmon SH, Nason KS. Optimal approach to the management of intrathoracic esophageal leak following esophagectomy: a systematic review. Am J Surg. 2014;208(4):536–43.
  36. Urschel JD. Esophagogastrostomy anastomotic leaks complicating esophagectomy: A review. Am J Surg. 1995;169(6):634–40.
  37. Robinson A, Kennedy L, Roper T, Khan M, Jaunoo S, Brighton Oesophago-Gastric Research Group. The management of chyle leak post-oesophagectomy for oesophageal carcinoma: a systematic review. Ann R Coll Surg Engl. 2022;104(7):480–9.
  38. Lou F, Sima CS, Adusumilli PS, Bains MS, Sarkaria IS, Rusch VW, et al. Esophageal Cancer Recurrence Patterns and Implications for Surveillance. J Thorac Oncol. 2013;8(12):1558–62.
  39. Vining P, Birdas TJ. Management of clinical T2N0 esophageal cancer: a review. J Thorac Dis. 2019;11(Suppl 12):S1629–32.
  40. Rhodin KE, Raman V, Jawitz OK, Voigt SL, Farrow NE. Patterns of Use of Induction Therapy for T2N0 Esophageal Cancer. Ann Thorac Surg. 2021;111(2):440–7.
  41. Speicher PJ, Ganapathi AM, Englum BR, Hartwig MG, Onaitis MW, D’Amico TA, et al. Induction therapy does not improve survival for clinical stage T2N0 esophageal cancer. J Thorac Oncol. 2014;9(8):1195–201.
  42. Samson P, Puri V, Robinson C, Lockhart C, Carpenter D, Broderick S, et al. Clinical T2N0 Esophageal Cancer: Identifying Pretreatment Characteristics Associated With Pathologic Upstaging and the Potential Role for Induction Therapy. Ann Thorac Surg. 2016;101(6):2102–11.
  43. Speicher PJ, Wang X, Englum BR, Ganapathi AM, Yerokun B, Hartwig MG, et al. Induction chemoradiation therapy prior to esophagectomy is associated with superior long-term survival for esophageal cancer. Esophagus. 2015;28(8):788–96.
  44. Rhodin KE, Vignesh R, D’Amico TA. Induction Therapy or Upfront Surgery? The Debate Rages On: Reply. Ann Thorac Surg. 2021;111(6):2085–6.
  45. Li B, Yang Y, Toker A, Yu B, Kang CH. International consensus statement on robot-assisted minimally invasive esophagectomy (RAMIE). J Thorac Dis. 2020;12(12):7387–401.
  46. Sarkaria IS, Rizk NP. Robotic-assisted minimally invasive esophagectomy: the Ivor Lewis approach. Thorac Surg Clin. 2014;24(2):211–22.
  47. He H, Wu Q, Wang Z, Zhang Y, Chen N, Fu J, et al. Short-term outcomes of robot-assisted minimally invasive esophagectomy for esophageal cancer: a propensity score matched analysis. J Cardiothorac Surg. 2018;13(1):52.
  48. Tagkalos E, Goense L, Hoppe-Lotichius M, Ruurda JP, Babic B. Robot-assisted minimally invasive esophagectomy (RAMIE) compared to conventional minimally invasive esophagectomy (MIE) for esophageal cancer: a propensity-matched analysis. Esophagus. 2020;33(4):doz060.