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Current Treatments of Esophageal and Esophagogastric Junction Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (31 August 2025) | Viewed by 6336

Special Issue Editor


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Guest Editor
Department of Upper Gastrointestinal Surgery, Dokkyo Medical University, Tochigi, Japan
Interests: esophageal cancer; colorectal cancer; surgery; chemotherapy

Special Issue Information

Dear Colleagues,

Esophageal and esophagogastric junction cancers have high morbidity and mortality rates worldwide. In the past, various therapies have been attempted in these cancers but returned unsatisfactory results. Recently, however, treatment outcomes have improved remarkably through the development of endoscopic treatment for early-stage cancer; minimally invasive and sophisticated surgical procedures including thoracoscopic and robot-assisted surgery; and advances in chemotherapy and chemoradiotherapy for advanced cancer. The emergence of immune checkpoint inhibitors has also led to remarkable improvements in the treatment of advanced cancers. In this Special Issue, we would like to introduce the latest treatment methods for esophageal cancer and esophagogastric junction cancer and to disseminate knowledge on their results and future issues.

Dr. Masanobu Nakajima
Guest Editor

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Keywords

  • esophageal cancer
  • esophagogastric junction cancer
  • endoscopic resection
  • surgery
  • minimally invasive surgery
  • robotic surgery
  • chemotherapy
  • chemoradiotherapy
  • immune checkpoint inhibitors

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Published Papers (4 papers)

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Research

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14 pages, 340 KB  
Article
FLOT Versus CROSS—What Is the Optimal Therapeutic Approach for Locally Advanced Adenocarcinoma of the Esophagus and the Esophagogastric Junction?
by Martin Leu, Hannes Mahler, Johanna Reinecke, Ute Margarethe König, Leif Hendrik Dröge, Manuel Guhlich, Benjamin Steuber, Marian Grade, Michael Ghadimi, Volker Ellenrieder, Stefan Rieken and Alexander Otto König
Cancers 2025, 17(15), 2587; https://doi.org/10.3390/cancers17152587 - 6 Aug 2025
Viewed by 1287
Abstract
Background/Objectives: Neoadjuvant radiochemotherapy and perioperative chemotherapy are both well-established treatment strategies for locally advanced adenocarcinoma of the esophagus (EAC) and the esophagogastric junction (AEGJ). However, recent knowledge controversially discusses whether neoadjuvant radiotherapy or perioperative chemotherapy represents superior therapeutic options to prolong survival or [...] Read more.
Background/Objectives: Neoadjuvant radiochemotherapy and perioperative chemotherapy are both well-established treatment strategies for locally advanced adenocarcinoma of the esophagus (EAC) and the esophagogastric junction (AEGJ). However, recent knowledge controversially discusses whether neoadjuvant radiotherapy or perioperative chemotherapy represents superior therapeutic options to prolong survival or cause less toxicity. Methods: We retrospectively analyzed 76 patients with locally advanced EAC or AEGJ treated at our tertiary cancer center between January 2015 and March 2023. Patients received either perioperative FLOT chemotherapy (n = 36) or neoadjuvant radiochemotherapy following the CROSS protocol (n = 40), followed by surgical resection and standardized follow-up. We compared survival outcomes, toxicity profiles, treatment compliance, and surgical results between the two groups. Results: There were no statistically significant differences between FLOT and CROSS treatments in five-year loco-regional controls (LRC: 61.5% vs. 68.6%; p = 0.81), progression-free survival (PFS: 33.9% vs. 42.8%; p = 0.82), overall survival (OS: 60.2% vs. 63.4%; p = 0.91), or distant controls (DC: 42.1% vs. 56.5%; p = 0.39). High-grade hematologic toxicities did not significantly differ between groups (p > 0.05). Treatment compliance was lower in the FLOT group, with 50% (18/36) not completing all the planned chemotherapy cycles, compared to 17.5% (7/40) in the CROSS group. All the patients in the CROSS group received the full radiotherapy dose. Surgical outcomes and post-surgical tumor status were comparable between the groups. Conclusions: Although perioperative chemotherapy with FLOT has recently become a standard of care for locally advanced EAC and AEGJ, neoadjuvant radiochemotherapy per the CROSS protocol remains a well-tolerated alternative. In appropriately selected patients, both approaches yield comparable oncological outcomes. Full article
(This article belongs to the Special Issue Current Treatments of Esophageal and Esophagogastric Junction Cancers)
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Review

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25 pages, 335 KB  
Review
Current Management of Locally Advanced Esophageal and Esophagogastric Junction Cancers: Clinical Evidence and Evolving Strategies
by Andrea Di Donato and Marc Van den Eynde
Cancers 2025, 17(22), 3603; https://doi.org/10.3390/cancers17223603 - 8 Nov 2025
Viewed by 1141
Abstract
The curative management of localized esophageal and esophagogastric junction (EGJ) cancers has undergone major changes over the past decade, shaped by multimodal strategies integrating chemotherapy, chemoradiotherapy, surgery, and more recently, immunotherapy. For esophageal squamous cell carcinoma (SCC), neoadjuvant or definitive chemoradiotherapy remains the [...] Read more.
The curative management of localized esophageal and esophagogastric junction (EGJ) cancers has undergone major changes over the past decade, shaped by multimodal strategies integrating chemotherapy, chemoradiotherapy, surgery, and more recently, immunotherapy. For esophageal squamous cell carcinoma (SCC), neoadjuvant or definitive chemoradiotherapy remains the standard of care in Western countries. In contrast, for adenocarcinoma (AC) of the esophagus and EGJ, perioperative chemotherapy has emerged as the preferred strategy. Despite these advances, long-term outcomes remain suboptimal, and recurrence continues to pose a major challenge, highlighting the need to optimize patient selection and treatment sequencing. The integration of immunotherapy in the perioperative or adjuvant setting has recently led to improvements in surrogate endpoints yet overall survival benefit remains under investigation. For patients with tumors harboring microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR), checkpoint inhibitors show exceptional activity, and non-operative management may be feasible in select cases. Conversely, human epidermal growth receptor 2 (HER2)-targeted strategies, although effective in metastatic disease, have not yet translated into practice-changing benefit in the curative setting. The role of circulating tumor deoxyribo nucleic acid (DNA) and functional imaging as real-time tools to assess response and guide treatment adaptation is also being actively explored. This review provides a comprehensive overview of current standards, ongoing developments, and future directions for the treatment of localized esophageal and EGJ cancers, with a focus on emerging personalization strategies and biomarker-driven approaches aimed at improving cure rates and minimizing treatment-related morbidity. Full article
(This article belongs to the Special Issue Current Treatments of Esophageal and Esophagogastric Junction Cancers)
11 pages, 422 KB  
Review
An Overview of the Treatment Strategy of Esophagogastric Junction Cancer
by Masatoshi Nakagawa, Masanobu Nakajima, Masaki Yoshimatsu, Yu Ueta, Noboru Inoue, Takahiro Ochiai, Shuhei Takise, Junki Fujita, Shinji Morita and Kazuyuki Kojima
Cancers 2025, 17(12), 1961; https://doi.org/10.3390/cancers17121961 - 12 Jun 2025
Viewed by 1152
Abstract
Background: The incidence of esophagogastric junction cancer (EGJC) is increasing in both Western and Eastern countries. Despite this trend, a globally accepted treatment strategy remains elusive due to the tumor’s anatomical complexity and variability in clinical practice. Aim: This review aims to provide [...] Read more.
Background: The incidence of esophagogastric junction cancer (EGJC) is increasing in both Western and Eastern countries. Despite this trend, a globally accepted treatment strategy remains elusive due to the tumor’s anatomical complexity and variability in clinical practice. Aim: This review aims to provide a comprehensive overview of current evidence regarding EGJC treatment, focusing on the surgical approach, extent of lymph node dissection, and perioperative therapy. Special attention is given to regional differences and the implications of recent clinical trials. Findings: Transhiatal and minimally invasive surgical approaches have demonstrated favorable safety profiles, particularly for Siewert type II tumors. Lymph node dissection strategies are increasingly tailored based on the extent of esophageal invasion. Pre- and postoperative chemotherapy and chemoradiotherapy are standard in the West, while East Asian countries are gradually adopting these approaches through trials such as RESOLVE (China) and PRODIGY (Korea). Immunotherapy has also emerged as a promising option following the CheckMate 577 trial. Conclusions: EGJC requires individualized treatment planning based on tumor characteristics and regional practices. While ongoing trials continue to inform optimal management, international collaboration and a stepwise, biomarker-informed approach will be essential to harmonize treatment strategies for this anatomically and therapeutically complex disease. Full article
(This article belongs to the Special Issue Current Treatments of Esophageal and Esophagogastric Junction Cancers)
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11 pages, 2661 KB  
Review
Development in Esophagectomy for Esophageal Cancer: The Current Standing Point of Robotic Surgery
by Yosuke Morimoto, Satoru Matsuda, Yuki Hirata, Yuki Hoshi, Masashi Takeuchi, Hirofumi Kawakubo and Yuko Kitagawa
Cancers 2025, 17(11), 1878; https://doi.org/10.3390/cancers17111878 - 4 Jun 2025
Cited by 1 | Viewed by 2261
Abstract
Despite advancements in multidisciplinary treatment, esophagectomy remains the primary curative treatment for esophageal cancer. Given that lymph node metastases can spread from the cervical to abdominal regions, three-field lymph node dissection has been established as a standard approach. However, this highly invasive procedure [...] Read more.
Despite advancements in multidisciplinary treatment, esophagectomy remains the primary curative treatment for esophageal cancer. Given that lymph node metastases can spread from the cervical to abdominal regions, three-field lymph node dissection has been established as a standard approach. However, this highly invasive procedure involves multiple anatomical regions—thoracic, abdominal, and cervical—leading to significant surgical burden. To reduce surgical invasiveness, minimally invasive esophagectomy (MIE) has become increasingly common worldwide. With its adoption and advancements in multidisciplinary therapy, discussions have emerged regarding the potential omission of lymph node dissection in selected cases. Since the introduction of robot-assisted minimally invasive esophagectomy (RAMIE) in 2004, this technique has progressively replaced conventional MIE. Robotic systems—equipped with a magnified 3D camera, articulated instruments, and tremor filtering—allow surgeons to perform complex procedures with greater precision than manual techniques. One randomized controlled trial (RCT) has demonstrated fewer postoperative complications with RAMIE compared to open esophagectomy. Additionally, RAMIE has been shown to enable more extensive lymph node dissection around the left recurrent laryngeal nerve than conventional MIE. However, the long-term oncological benefits of RAMIE remain unproven, as no RCTs have definitely confirmed its impact on long-term survival in esophageal cancer patients. Ongoing randomized trials are expected to provide further insights into its prognostic benefits. Full article
(This article belongs to the Special Issue Current Treatments of Esophageal and Esophagogastric Junction Cancers)
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