Esophageal Cancer Symptoms, Stages, and Treatment – Patient Guide
In this article
What Is Esophageal Cancer?
Rather than a single disease, esophageal cancer involves tumors that arise in the same organ but have different biology, risk factors, and, increasingly, treatments; it encompasses two different types of cancer under one umbrella term: the upper/middle esophagus is more commonly affected by squamous cell carcinoma (SCC) , while the lower section near the esophagogastric junction (EGJ) is affected by adenocarcinoma. The past few years have seen a succession of new FDA approvals at an unprecedented pace in the treatment of this group of diseases, particularly in immunotherapy — most recently (25 August 2026), a new targeted therapy–immunotherapy combination received approval for HER2-positive disease, explicitly including "esophageal adenocarcinoma" for the first time. This guide covers all the details, from the causes and diagnosis of the disease to staging and the latest treatment options.
While squamous cell carcinoma (SCC) is primarily associated with smoking, alcohol, and consumption of very hot drinks/foods, adenocarcinoma mainly develops in the setting of chronic reflux (GERD) and Barrett's esophagus. These two types have different geographical distributions (SCC predominates in Asia/East Africa, while adenocarcinoma is increasing in Western countries), different staging details, and markedly different treatment algorithms — particularly for immunotherapy and targeted therapies. The treatment sections in this guide therefore address SCC and adenocarcinoma separately.
Esophageal Anatomy
The esophagus is a muscular tube approximately 25 cm long that carries food and liquids from the mouth to the stomach during swallowing. The upper esophageal sphincter at its upper end opens during swallowing to allow food to enter the esophagus; at its lower end, it joins the stomach at a point called the esophagogastric junction (EGJ), where the lower esophageal sphincter prevents stomach contents from flowing backward (reflux).
The esophagus is anatomically divided into three regions: the cervical (neck) region, the thoracic (chest) region (with its upper, middle, and lower sections), and the abdominal (belly) region, where it joins the stomach. This distinction in location matters because the tumor's position in the esophagus directly affects both the likely histological type (SCC is more likely in the upper/middle regions and adenocarcinoma in the lower region) and the surgical approach.
How Common Is It? (Current Statistics)
According to the International Agency for Research on Cancer's (IARC) "Global cancer statistics 2024" report (Sung H, et al., CA: A Cancer Journal for Clinicians, published July 8, 2026, DOI: 10.3322/caac.70090), worldwide data for 2024 reported approximately 494.320 new cases of esophageal cancer (ranking 13. in incidence) and 441.994 deaths due to esophageal cancer (ranking 7. among cancer deaths — a cancer that is disproportionately deadly relative to its incidence) were reported. The age-standardized incidence is 7,1 per 100.000 in men and 2,3 per 100.000 in women; the highest rates occur in East Asia, East Africa, and South-Central Asia. The preceding GLOBOCAN 2022 report (Bray F, et al., CA Cancer J Clin, 2024) reported 511.054 cases; this small decrease in the 2024 data most likely reflects methodological updates, and readers should be aware that they may encounter both figures online.
According to the American Cancer Society's "Cancer Statistics, 2026" report (Siegel RL, et al., CA: A Cancer Journal for Clinicians, published on 13 January 2026, DOI: 10.3322/caac.70043), in 2026 approximately 22.530 new cases of esophageal cancer (17.580 men, 4.950 women) and 16.290 deaths are expected. The median age at diagnosis is 69, and approximately %90 of cases occur at age 55 or older. The 5-year relative survival by stage (SEER, 2015-2021 diagnosis cohort) is %49 for localized disease, %28 for regional spread, and %5 for distant metastasis; across all stages combined, it is approximately %22 — this low overall survival rate largely reflects the fact that most patients have advanced disease at diagnosis.
According to the GLOBOCAN 2024 Türkiye country profile, approximately 2.109 new cases of esophageal cancer and 1.820 deaths are reported annually, placing esophageal cancer 20. in incidence among all cancers and 14. among causes of death — the disproportionately high mortality relative to incidence is consistent with the global trend.
Risk Factors
The risk factors for squamous cell carcinoma (SCC) and adenocarcinoma differ substantially:
| Squamous Cell Carcinoma (SCC) | Adenocarcinoma |
|---|---|
| Smoking | Chronic gastroesophageal reflux (GERD) |
| Excessive alcohol consumption (a particularly synergistic effect with smoking) | Barrett's esophagus |
| Consumption of very hot drinks/foods (may increase the risk ~5-fold according to one study) | Obesity |
| Betel leaf chewing (in some Asian populations) | Smoking (with a weaker association) |
| History of esophageal scarring/stricture due to ingestion of caustic substances | Male sex (adenocarcinoma is markedly more common in men) |
Regular consumption of particularly hot drinks (approximately 60°C or above) can cause chronic thermal injury to the esophageal mucosa and increase the risk of SCC; some population studies have reported an approximately 5-fold increase in this risk. This has been proposed as one reason for the high frequency of SCC in certain regions where hot tea/coffee consumption is common.
Barrett's Esophagus and Adenocarcinoma Risk
Barrett's esophagus is a condition in which the normal squamous epithelial cells in the lower esophagus are replaced by glandular epithelium resembling stomach/small intestinal cells (intestinal metaplasia) as a result of longstanding chronic reflux (GERD). This change markedly increases the risk of developing adenocarcinoma compared with the general population — regular endoscopic surveillance (monitoring) is therefore recommended for patients diagnosed with Barrett's esophagus to detect the development of dysplasia early. As the degree of dysplasia increases (low-grade → high-grade dysplasia), surveillance becomes more frequent, and in some cases, endoscopic ablative treatments (such as radiofrequency ablation) or endoscopic resection may be considered.
For people at high risk of developing esophageal cancer (such as those with a history of longstanding reflux, Barrett's esophagus, or obesity), regular endoscopic evaluation may help detect a potential cancer at an early stage.
Symptoms
- Difficulty swallowing (dysphagia) — usually with solid foods first, then liquids
- Persistent indigestion or heartburn
- Unexplained weight loss
- Pain behind the breastbone or in the throat
- Hoarseness or chronic cough
- Anemia (low red blood cell levels) or occult/visible bleeding
These symptoms can also arise from many benign causes other than esophageal cancer, but progressive dysphagia in particular should always be evaluated by a physician — the esophagus has a lumen wide enough that a tumor may not cause symptoms until it blocks a substantial part of its diameter; this is one reason why diagnosis often occurs at a relatively advanced stage.
How Is It Diagnosed?
Endoscopy and Biopsy
Upper gastrointestinal endoscopy is the gold standard for diagnosing esophageal cancer; a thin, flexible camera directly visualizes the inner surfaces of the esophagus, stomach, and duodenum, and a biopsy is taken from suspicious areas for pathological examination; this examination determines whether the cancer is SCC or adenocarcinoma.
Imaging for Staging
After the diagnosis is confirmed, imaging of the chest/abdomen/pelvis using computed tomography (CT) is used to assess the tumor's local spread and possible distant metastases. Endoscopic ultrasonography (EUS) is more sensitive than CT for assessing the depth of the tumor in the esophageal wall (T stage) and the surrounding lymph nodes. PET-CT uses a radioactive substance to help screen for distant metastases and is now performed alongside CT at most centers. In suspicious cases, particularly to assess occult spread within the abdomen, laparoscopy (placing a camera into the abdominal cavity through a small incision) may also be used.
Molecular (Biomarker) Tests
Testing biomarkers that directly guide treatment selection is now considered standard for every patient diagnosed with metastatic esophageal cancer; the biomarkers investigated vary according to the histological type:
| Biomarker | Histology in Which It Is Tested | Clinical Significance |
|---|---|---|
| PD-L1 (CPS score) | Both SCC and adenocarcinoma | Determines the use of immunotherapy combinations (pembrolizumab, nivolumab, tislelizumab) and, in some cases, the scope of approval |
| HER2 (ERBB2) | Adenocarcinoma/EGJ | Determines eligibility for HER2-targeted therapies such as trastuzumab, trastuzumab deruxtecan, and zanidatamab |
| Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR) | Adenocarcinoma/EGJ (rarely SCC) | Indicates the possibility of an exceptional response to immunotherapy |
| Claudin 18.2 (CLDN18.2) | Adenocarcinoma/EGJ | Determines eligibility for zolbetuximab treatment (see below — this approval currently applies specifically to gastric/EGJ disease) |
Staging: The TNM System
In esophageal cancer, the stage is determined by a combination of several factors, including the depth of tumor invasion into the esophageal wall (T), the number of involved lymph nodes (N), the tumor's location in the esophagus, and histological type/grade — the same "Stage II" or "Stage III" label can therefore represent different T/N combinations in different patients. Below are the detailed subdivisions of the staging system, followed by a simplified summary that readers should keep in mind.
Stage 0
The cancer is confined to the layer lining the inner surface of the esophagus (also called high-grade dysplasia).
Stage I (IA and IB)
Stage IA: The cancer has spread to the mucosa or thin muscle layer; the cancer cells are grade 1 or their grade is unknown.
Stage IB: The cancer has spread to the mucosa/thin muscle layer and is grade 1; or it has spread to the submucosal layer and may be of any grade.
Stage II (IIA and IIB)
Stage IIA: The cancer has spread to the thick muscle layer (grade 2-3 or unknown); or it has spread to the connective tissue in the lower esophagus.
Or: grade 1 cancer cells in the connective tissue layer of the middle/upper esophagus.
Stage IIB: The cancer has spread to the muscle layer (grade 2-3, in the middle/lower esophagus).
Or: it has spread to the connective tissue layer, with unknown grade/location.
Or: it has spread to the mucosa/thin muscle/submucosal layer, and cancer may be present in 1-2 nearby lymph nodes.
Stage III (IIIA and IIIB)
Stage IIIA: It has spread to the mucosa/thin muscle/submucosal layer, and 3-6 lymph nodes may be involved; or it has spread to the thick muscle layer, and 1-2 lymph nodes may be involved.
Stage IIIB: It has spread to the connective tissue layer, and 1-6 lymph nodes may be involved.
Or: it has spread to structures such as the diaphragm, azygos vein, pleura, pericardium, or peritoneum, and 0-2 lymph nodes may be involved.
Stage IV (IVA and IVB)
Stage IVA: It has spread to the diaphragm, azygos vein, pleura, pericardium, or peritoneum, and 3-6 lymph nodes may be involved.
Or: it has spread to structures such as the aorta, airways, or spine, and 0-6 lymph nodes may be involved.
Or: cancer may be present in 7 or more lymph nodes (without distant organ involvement).
Stage IVB: The cancer has spread to distant parts of the body (such as the liver or lungs).
Stage I: The cancer has not extended beyond the thick muscle layer of the esophageal wall. Stage II: The cancer has spread beyond the thick muscle layer and may have reached 1-2 nearby lymph nodes. Stage III: The cancer has extended beyond the outer layer of the esophagus and spread to nearby tissues; it may involve several lymph nodes but has not spread to other organs. Stage IV: The cancer has spread to nearby tissues/organs or metastasized to distant parts of the body.
Treatment Approach: Multidisciplinary Assessment
Esophageal cancer treatment should be planned by medical oncologists, surgeons, radiation oncologists, gastroenterologists, radiologists, pathologists, dietitians, and nurses working together as a multidisciplinary team . The treatment plan is individualized according to the tumor's histological type (SCC/adenocarcinoma), location, stage, biomarker profile, and the patient's general condition.
Surgical Treatment
- Endoscopic mucosal resection (EMR)/submucosal dissection: removal of the tumor from the inner surface of the esophagus using an endoscope — suitable only for very early-stage disease (Stage 0/early IA)
- Esophagectomy: removal of the section of the esophagus containing the tumor (sometimes the entire esophagus) together with nearby lymph nodes — it can be performed using an open or minimally invasive (laparoscopic/robotic) technique
After esophagectomy, the surgeon must reconstruct the digestive tract: the stomach is usually pulled up into the chest cavity to connect with the remaining esophagus (in some cases, a section of the intestine may also be used). This is a major life change that directly affects the patient's long-term eating habits.
Treatment of Early-Stage and Locally Advanced Squamous Cell Carcinoma (SCC)
Early-stage SCC is generally treated with surgery alone (EMR or esophagectomy). For locally advanced SCC, the standard approach is preoperative chemoradiotherapy (neoadjuvant chemoradiotherapy):
According to the CROSS study (van Hagen P, et al., New England Journal of Medicine, 2012; 10-year follow-up: Oppedijk V/Shapiro, Journal of Clinical Oncology, 2021), neoadjuvant chemoradiotherapy consisting of carboplatin+paclitaxel with concurrent radiotherapy, followed by surgery, markedly improved overall survival compared with surgery alone. This regimen remains the standard neoadjuvant approach for locally advanced SCC and retains its place in SCC despite the increasing prominence of FLOT-based perioperative chemotherapy in adenocarcinoma.
For patients with pathological residual disease after neoadjuvant chemoradiotherapy + R0 (complete) surgical resection, adjuvant nivolumab on 20 May 2021 received FDA approval (regardless of histology — covering both SCC and adenocarcinoma). According to the CheckMate 577 study (Kelly RJ, et al., New England Journal of Medicine, 2021), disease-free survival nearly doubled (22,4 months versus 11,0 months; HR 0,69).
For patients who are unsuitable for surgery or do not want surgery, chemoradiotherapy alone with curative intent can be used as a treatment option; these patients are monitored for recurrence through regular follow-up appointments.
Treatment of Metastatic Squamous Cell Carcinoma (SCC)
First-line treatment for metastatic SCC is generally a combination of chemotherapy + immunotherapy; the choice of combination varies according to PD-L1 status.
According to the CheckMate 648 study (Doki Y, et al., New England Journal of Medicine, 2022), in advanced/metastatic SCC, nivolumab+chemotherapy or nivolumab+ipilimumab prolonged overall survival compared with chemotherapy alone, and both combinations on 27 May 2022 received FDA approval (regardless of PD-L1 status, although the benefit is more pronounced in patients with PD-L1≥%1: nivo+chemo HR 0,54 versus HR 0,74 in the overall population).
According to the KEYNOTE-590 study (Sun JM, et al., Lancet, 2021), the pembrolizumab+chemotherapy combination on 22 March 2021 received FDA approval for metastatic/locally advanced esophageal or EGJ cancer (including SCC and adenocarcinoma, in patients unsuitable for surgery/curative chemoradiotherapy) (OS HR 0,73).
Tislelizumab received approvals for two different treatment lines in SCC within a short interval: as second-line monotherapy (in patients previously treated with chemotherapy that did not include a PD-1/PD-L1 inhibitor), based on the RATIONALE-302 study, on 14 March 2024 (OS 8,6 months versus 6,3 months; HR 0,70); and as first-line therapy in combination with chemotherapy (only in patients with PD-L1 expression ≥%1 — unlike CheckMate 648/KEYNOTE-590, this is not an all-comers approval), based on the RATIONALE-306 study, on 4 March 2025 (OS 17,2 months versus 10,6 months; HR 0,66; ORR %63 versus %42). As of the date of this research, tislelizumab is not authorized by TİTCK in Türkiye (see the Türkiye section below).
Toripalimab has "orphan drug" status for esophageal cancer in the United States, but as of the date of this research, it does not have FDA approval; it has received approval in China (NMPA) and recently in Europe (in combination with chemotherapy). Other Chinese-origin anti-PD-1 agents, such as camrelizumab and sintilimab, also lack US approval for SCC.
Perioperative/Neoadjuvant Treatment: Esophageal and EGJ Adenocarcinoma
According to the FLOT4 study (Al-Batran SE, et al., Lancet, 2019), perioperative (before and after surgery) chemotherapy with the 5-FU/folinic acid/oxaliplatin/docetaxel (FLOT) combination markedly prolonged overall survival compared with the older ECF/ECX regimen. In current (2026) NCCN-aligned practice, for resectable esophageal/EGJ adenocarcinoma , FLOT-based perioperative chemotherapy is increasingly taking precedence over CROSS-type neoadjuvant chemoradiotherapy — whereas the CROSS regimen remains standard for SCC (see above).
According to the MATTERHORN study (Janjigian YY, et al., New England Journal of Medicine, 2025), adding durvalumab to FLOT markedly increased pathological complete response and event-free survival (EFS HR 0,71; OS HR 0,78; pathological complete response %19,2 versus %7,2), and this combination on 25 November 2025 received FDA approval. An important detail: the FDA label explicitly defines this approval as "resectable gastric or gastroesophageal junction (EGJ) adenocarcinoma" and does not include the term "esophageal adenocarcinoma" — its use in pure esophageal adenocarcinoma therefore rests on guideline/practice extrapolation rather than the label text. This nuance contrasts directly with the zanidatamab+tislelizumab approval below.
Treatment of Metastatic Esophageal Adenocarcinoma and EGJ Cancer
The treatment of metastatic esophageal adenocarcinoma and EGJ cancer largely follows the treatment algorithm used for gastric cancer (there are strong biological similarities between these two disease groups) — for detailed information, our gastric cancer guide is also available for you to consult.
For HER2-positive metastatic disease, the zanidatamab-hrii + tislelizumab-jsgr combination (brand name Ziihera), based on the HERIZON-GEA-01 study, on 25 August 2026 received FDA approval (median overall survival in Arm C: 26,4 months versus 19,2 months; HR 0,72; progression-free survival: 12,4 months versus 8,1 months; HR 0,63). Among the new generation of treatments discussed here, the FDA label text makes this approval noteworthy as the first approval to explicitly use the combined wording "gastric, gastroesophageal junction, or esophageal adenocarcinoma" — unlike zolbetuximab, the original trastuzumab deruxtecan approval, and durvalumab+FLOT, it explicitly includes patients with pure esophageal adenocarcinoma.
Also in the first line: for HER2-positive patients, together with chemotherapy, trastuzumab; for PD-L1-positive patients (at the appropriate CPS threshold), together with chemotherapy, nivolumab or pembrolizumab may be used.
If progression occurs after first-line treatment, the usual second-line choices are the ramucirumab+paclitaxel combination, for HER2-positive patients trastuzumab deruxtecan, and for MSI-high/dMMR patients pembrolizumab . In the third line, chemotherapy with oral TAS-102 (trifluridine+tipiracil) may be used as a treatment option.
The DESTINY-Gastric04 study (Shitara K/Ando M, et al., New England Journal of Medicine, 2025) tested trastuzumab deruxtecan against ramucirumab+paclitaxel in the second line and reported a favorable overall survival result; however, as of the date of this research, no separate FDA label update/approval based on these results could be found — this finding should therefore currently be considered "evidence" and should not yet be presented as an official change in approval.
Supportive Treatments
A substantial proportion of patients with esophageal cancer develop difficulty swallowing (dysphagia) because the tumor narrows the esophageal lumen; this can result from both the disease itself and treatment (for example, mucositis caused by chemoradiotherapy). Supportive approaches to preserve nutrition and quality of life should be planned alongside curative or palliative treatment.
Esophageal Stent Placement
For advanced, obstructing esophageal tumors or patients unsuitable for curative treatment, endoscopic placement of a self-expanding metal stent is a common palliative procedure that can rapidly restore swallowing by opening the lumen. A stent can also be used to close fistulas that may form between the esophagus and the trachea/bronchi.
Nutritional Support
For patients with significant swallowing difficulties or planned surgery/chemoradiotherapy, a nutrition plan should be developed with a dietitian to ensure adequate calorie and protein intake. Some patients with severe dysphagia may temporarily need feeding through a nasogastric tube or percutaneous endoscopic gastrostomy (PEG)/jejunostomy to provide nutritional support. Dysphagia (difficulty swallowing) is discussed in more detail in our separate guide.
Treatment Side Effects
| Treatment | Common Side Effects |
|---|---|
| Surgery (esophagectomy) | Anastomotic leak, pneumonia, vocal cord paralysis, long-term reflux/dumping syndrome, permanent changes in eating habits |
| Chemoradiotherapy (CROSS regimen) | Esophagitis/mucositis (pain during swallowing), fatigue, nausea, bone marrow suppression, skin reactions |
| Perioperative chemotherapy (FLOT) | Neutropenia, nausea/vomiting, peripheral neuropathy (oxaliplatin), diarrhea, fatigue |
| Immunotherapy (nivolumab, pembrolizumab, tislelizumab, durvalumab) | Immune-related side effects: colitis, hepatitis, pneumonitis, inflammation of endocrine glands such as the thyroid/pituitary, skin rash — generally different from chemotherapy side effects and sometimes delayed in onset |
| HER2-targeted therapies (trastuzumab, trastuzumab deruxtecan, zanidatamab) | Reduced cardiac function (particularly with trastuzumab), risk of interstitial lung disease/pneumonitis associated with trastuzumab deruxtecan (requires monitoring) |
| Ramucirumab | Hypertension, risk of bleeding, delayed wound healing, proteinuria |
The side effect profile varies markedly with the drug/regimen combination; patients should promptly report new or worsening symptoms to their treatment team (particularly diarrhea, shortness of breath, yellowing of the skin, or chest pain).
Global Approval and Evidence Timeline
KEYNOTE-590: Pembrolizumab FDA ApprovalMilestone
Pembrolizumab+chemotherapy received first-line approval for metastatic/locally advanced esophageal and EGJ cancer (SCC and adenocarcinoma).
CheckMate 577: Adjuvant NivolumabMilestone
Approval of adjuvant nivolumab for residual disease after neoadjuvant chemoradiotherapy+surgery, regardless of histology.
CheckMate 648: Nivolumab CombinationsMilestone
First-line approvals of nivolumab+chemotherapy and nivolumab+ipilimumab for metastatic SCC.
Tislelizumab (RATIONALE-302) FDA Approval
Approval as second-line monotherapy for SCC — in patients who have not previously received a PD-1/PD-L1 inhibitor.
Zolbetuximab FDA Approval
Approval for CLDN18.2-positive gastric/EGJ adenocarcinoma — the label text does not explicitly cover the esophagus.
Tislelizumab (RATIONALE-306) FDA Approval
First-line combination approval for SCC — only for patients with PD-L1≥%1.
MATTERHORN: Durvalumab+FLOT FDA Approval
Perioperative durvalumab+FLOT received approval for resectable gastric/EGJ adenocarcinoma (esophageal adenocarcinoma is not explicitly included in the label).
Zanidatamab+Tislelizumab (HERIZON-GEA-01) FDA ApprovalLatest
Approval for HER2-positive metastatic disease — for the first time in this generation of treatments, the label explicitly includes "esophageal adenocarcinoma."
The Situation in Türkiye: TİTCK Authorization and SGK Reimbursement
The FLOT components (5-FU, folinic acid, oxaliplatin, docetaxel), the CROSS regimen components (carboplatin, paclitaxel), and radiotherapy are widely covered by SGK in Türkiye without additional restrictions specific to esophageal cancer.
Under the provisions of SUT (Health Implementation Communiqué), SGK reimburses nivolumab for metastatic SCC as second-line monotherapy . Adjuvant use (the CheckMate 577 indication) and first-line nivolumab+chemotherapy for metastatic EGJ cancer/adenocarcinoma (HER2-negative, PD-L1≥%5) are covered with a duration limit of 24 months. However, the nivolumab+ipilimumab combination could not be found within SUT coverage for the SCC indication.
As of the date of this research, pembrolizumab's first-line esophageal/EGJ cancer indication based on KEYNOTE-590 could not be identified in the SUT lists (a similar pattern was observed for the pembrolizumab indication in nasopharyngeal cancer). Patients and physicians should confirm the current coverage status using SGK/TİTCK sources.
As of the date of this research, tislelizumab has not been authorized by TİTCK in Türkiye and is therefore also outside SGK reimbursement coverage. Our separate article on tislelizumab discusses its current authorization status.
For HER2-positive metastatic disease, trastuzumab is reimbursed by SGK under SUT provision 4.2.14.C (the provision explicitly mentions EGJ).
Although both drugs are authorized by TİTCK, they could not be found in SGK reimbursement lists as of the date of this research; access is largely obtained through individual applications/lawsuits. For ramucirumab, a Court of Cassation ruling dated January 2026 was reported to have favored patients by requiring SGK to cover the drug — however, such rulings are based on individual legal proceedings and do not mean automatic/guaranteed coverage for every patient.
Frequently Asked Questions
- What is the most important difference between the squamous cell and adenocarcinoma types of esophageal cancer?
- The two types arise from different risk factors (SCC: smoking/alcohol/hot drinks; adenocarcinoma: reflux/Barrett's esophagus), have different geographical distributions, and are increasingly managed with separate treatment algorithms — particularly for immunotherapy/targeted therapies.
- Does everyone with Barrett's esophagus develop cancer?
- No. Barrett's esophagus increases the risk of adenocarcinoma compared with the general population, but the vast majority of these patients do not develop cancer; regular endoscopic surveillance is therefore recommended to identify the risk early.
- Which biomarkers should be tested in esophageal cancer?
- In metastatic disease, testing PD-L1, HER2 (particularly in adenocarcinoma/EGJ), MSI-H/dMMR, and CLDN18.2 in adenocarcinoma is a standard practice that directly affects treatment selection.
- Why is the zanidatamab+tislelizumab approval considered important?
- For HER2-positive metastatic disease, this combination is the first approval in this generation of treatments whose FDA label explicitly includes "esophageal adenocarcinoma" — unlike many earlier "gastric/EGJ" approvals.
- What do tislelizumab's two separate approvals mean?
- Tislelizumab was first approved for SCC (March 2024) as second-line monotherapy, then (March 2025) as first-line therapy in combination with chemotherapy only for patients with PD-L1≥%1 — these are separate approvals covering two different clinical scenarios.
References:
- Sung H, et al. Global cancer statistics 2024. CA Cancer J Clin. 2026. DOI: 10.3322/caac.70090.
- Bray F, et al. Global cancer statistics 2022. CA Cancer J Clin. 2024.
- Siegel RL, et al. Cancer Statistics, 2026. CA Cancer J Clin. 2026. DOI: 10.3322/caac.70043.
- van Hagen P, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer (CROSS). N Engl J Med. 2012.
- Oppedijk V, Shapiro J, et al. CROSS 10-year follow-up. J Clin Oncol. 2021.
- Kelly RJ, et al. Adjuvant nivolumab in resected esophageal/GEJ cancer (CheckMate 577). N Engl J Med. 2021.
- Doki Y, et al. Nivolumab combinations in advanced esophageal SCC (CheckMate 648). N Engl J Med. 2022.
- Sun JM, et al. Pembrolizumab plus chemotherapy in esophageal cancer (KEYNOTE-590). Lancet. 2021.
- Al-Batran SE, et al. Perioperative FLOT chemotherapy (FLOT4). Lancet. 2019.
- Janjigian YY, et al. Perioperative durvalumab plus FLOT (MATTERHORN). N Engl J Med. 2025.
- Shitara K, Ando M, et al. Trastuzumab deruxtecan in gastric/GEJ cancer (DESTINY-Gastric04). N Engl J Med. 2025.
- FDA approval announcements: zanidatamab-tislelizumab (HERIZON-GEA-01), tislelizumab (RATIONALE-302, RATIONALE-306), zolbetuximab.
- Relevant articles of Türkiye's Health Implementation Communiqué (SUT), TİTCK drug license lists.
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