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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (18 October 2022) | Viewed by 32817

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Dr. Matthias Reeh

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Department of General, Visceral and Thoracic Surgery, University Medical Center, Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
Interests: esophageal adenocarcinoma; gastric cancers; colorectal cancer; circulating tumor cells

Special Issue Information

Dear Colleagues,

This Special Issue is about Oesophageal adenocarcinoma (OEA). OEA is among the most lethal conditions gastroenterologists face today, with only 16% of patients surviving 5 years and a median survival time of less than 1 year. Unfortunately, little progress has been made in improving survival and patients’ outcome. Oesophageal adenocarcinoma usually presents at a late stage, with most patients presenting with T3 or T4 disease and, thus, high mortality rates. Very few treatment regimens are available. What is more, the incidence of OEA has increased in the last 40 years, by approximately 600% from the 1970s. The reasons for this increase and tumor biology in particular are poorly understood. Treatment of OEA has evolved in recent years, with several new treatment techniques that lead to improvements in oncology, gastroenterology, and surgery. However, recent studies have shown that we are still far away from a clear understanding of oesophageal adenocarcinoma.

Here, we welcome papers outlining tumor biology, diagnostics, and treatment modalities of Oesophageal adenocarcinoma.

Dr. Matthias Reeh
Guest Editor

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Keywords

oesophageal adenocarcinoma (OEA)
tumor biology
diagnostics
treatment

Published Papers (13 papers)

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Editorial

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3 pages, 188 KiB

Open AccessEditorial

Oesophageal Adenocarcinomas: Where Do We Stand Today?

by Karl-Frederick Karstens, Björn Ole Stüben and Matthias Reeh

Cancers 2021, 13(1), 109; https://doi.org/10.3390/cancers13010109 - 31 Dec 2020

Cited by 3 | Viewed by 1558

Abstract

Oesophageal cancers (oesophageal squamous cell carcinomas and adenocarcinomas) haven been responsible for more than one million deaths worldwide in 2018 [...] Full article

(This article belongs to the Special Issue Oesophageal Adenocarcinoma)

Research

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15 pages, 1738 KiB

Open AccessArticle

Correlations between Molecular Alterations, Histopathological Characteristics, and Poor Prognosis in Esophageal Adenocarcinoma

by Arianna Orsini, Luca Mastracci, Isotta Bozzarelli, Anna Ferrari, Federica Isidori, Roberto Fiocca, Marialuisa Lugaresi, Antonietta D’Errico, Deborah Malvi, Erica Cataldi-Stagetti, Paola Spaggiari, Anna Tomezzoli, Luca Albarello, Ari Ristimäki, Luca Bottiglieri, Kausilia K. Krishnadath, Riccardo Rosati, Uberto Fumagalli Romario, Giovanni De Manzoni, Jari Räsänen, Giovanni Martinelli, Sandro Mattioli, Elena Bonora and on behalf of the EACSGE Consortium Show full author list Hide full author list

Cancers 2023, 15(5), 1408; https://doi.org/10.3390/cancers15051408 - 23 Feb 2023

Cited by 2 | Viewed by 1628

Abstract

Esophageal adenocarcinoma (EAC) is a severe malignancy with increasing incidence, poorly understood pathogenesis, and low survival rates. We sequenced 164 EAC samples of naïve patients (without chemo-radiotherapy) with high coverage using next-generation sequencing technologies. A total of 337 variants were identified across the whole cohort, with TP53 as the most frequently altered gene (67.27%). Missense mutations in TP53 correlated with worse cancer-specific survival (log-rank p = 0.001). In seven cases, we found disruptive mutations in HNF1alpha associated with other gene alterations. Moreover, we detected gene fusions through massive parallel sequencing of RNA, indicating that it is not a rare event in EAC. In conclusion, we report that a specific type of TP53 mutation (missense changes) negatively affected cancer-specific survival in EAC. HNF1alpha was identified as a new EAC-mutated gene. Full article

(This article belongs to the Special Issue Oesophageal Adenocarcinoma)

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14 pages, 1124 KiB

Open AccessArticle

HER2-Positive Gastroesophageal Cancers Are Associated with a Higher Risk of Brain Metastasis

by Gary Tincknell, Asma Naveed, Jane Nankervis, Ayesha Mukhtiar, Ann-Katrin Piper, Therese M. Becker, Lorraine Chantrill, Morteza Aghmesheh, Kara Lea Vine, Marie Ranson and Daniel Brungs

Cancers 2022, 14(23), 5754; https://doi.org/10.3390/cancers14235754 - 23 Nov 2022

Cited by 4 | Viewed by 1574

Abstract

Brain metastasis from gastroesophageal adenocarcinomas (GOCs) is a rare but a devastating diagnosis. Human epidermal growth factor receptor 2 (HER2) is a prognostic and predictive biomarker in GOCs. The association of HER2 with GOC brain metastasis is not known. We performed a retrospective analysis of patients with GOCs with known HER2 status between January 2015 and November 2021. HER2 was assessed on either the primary tumour or metastasis by immunohistochemistry or in situ hybridization. The diagnosis of brain metastasis was made on standard imaging techniques in patients with symptoms or signs. HER2 results were available for 201 patients, with 34 patients (16.9%) HER2 positive. A total of 12 patients developed symptomatic brain metastasis from GOCs, of which 7 (58.3%) were HER2 positive. The development of symptomatic brain metastasis was significantly higher in the HER2-positive GOCs (OR8.26, 95%CI 2.09–35.60; p = 0.0009). There was no significant association of HER2 status and overall survival in patients with brain metastasis. Although the rate of brain metastasis remains low in GOCs, the incidence of symptomatic brain metastasis was significantly higher in patients with HER2-positive tumours. Full article

(This article belongs to the Special Issue Oesophageal Adenocarcinoma)

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13 pages, 1474 KiB

Open AccessArticle

Completion of FLOT Therapy, Regardless of Tumor Regression, Significantly Improves Overall Survival in Patients with Esophageal Adenocarcinoma

by Björn-Ole Stüben, Jakob Stuhlfelder, Marius Kemper, Michael Tachezy, Tarik Ghadban, Jakob Robert Izbicki, Carsten Bokemeyer, Marianne Sinn, Karl-Frederick Karstens and Matthias Reeh

Cancers 2022, 14(4), 1084; https://doi.org/10.3390/cancers14041084 - 21 Feb 2022

Cited by 3 | Viewed by 3361

Abstract

Esophageal cancer is the eighth most common cancer worldwide, with poor prognosis and high mortality. The combination of surgery and systemic therapy provide the best chances for long-term survival. The purpose of this study was to analyze the impact of the FLOT protocol on the overall survival of patients following surgery for esophageal adenocarcinoma, with a focus on the patients who did not benefit in terms of pathological remission from the neoadjuvant therapy. A retrospective analysis of all the patients who underwent esophagectomies from 2012 to 2017 for locally advanced adenocarcinomas of the esophagus at a tertiary medical center was performed. The results show that the completion of systemic therapy, regardless of the tumor regression grading, had a significant positive impact on the overall survival. The patients with complete regression and complete systemic therapy showed the best outcomes. Anastomotic insufficiency did not negatively impact the long-term survival, while complications of the systemic therapy led to significantly reduced overall survival. We conclude that adjuvant systemic therapy should, when possible, always be completed, regardless of the tumor regression, following an esophagectomy. Full article

(This article belongs to the Special Issue Oesophageal Adenocarcinoma)

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17 pages, 1730 KiB

Open AccessArticle

High Serum Levels of Wnt Signaling Antagonist Dickkopf-Related Protein 1 Are Associated with Impaired Overall Survival and Recurrence in Esophageal Cancer Patients

by José Giron Ramirez, Daniel J. Smit, Fabrice Viol, Jörg Schrader, Tarik Ghadban, Klaus Pantel, Jakob R. Izbicki and Matthias Reeh

Cancers 2021, 13(19), 4980; https://doi.org/10.3390/cancers13194980 - 04 Oct 2021

Cited by 6 | Viewed by 2189

Abstract

Dickkopf-related protein 1 (DKK1), an antagonist of the canonical Wnt pathway, has received tremendous attention over the past years as its dysregulation is said to be critically involved in a wide variety of gastrointestinal cancers. However, the potential clinical implications of DKK1 remain poorly understood. Although multimodal treatment options have been implemented over the past years, esophageal cancer (EC) patients still suffer from poor five-year overall survival rates ranging from 15% to 25%. Especially prognostic factors and biomarkers for risk stratification are lacking to choose the most beneficial treatment out of the emerging landscape of different treatment options. In this study, we analyzed the serum DKK1 (S-DKK1) levels of 91 EC patients prior to surgery in a single center study at the University Medical Center Hamburg-Eppendorf by enzyme-linked immunosorbent assay. High levels of S-DKK1 could be especially observed in patients suffering from esophageal adenocarcinoma which may promote the hypothesis of a crucial role of DKK1 in inflammation. S-DKK1 levels of ≥5800 pg/mL were shown to be associated with unfavorable five-year survival rates and the presence of CTCs. Interestingly, significantly lower S-DKK1 levels were detected in patients after neoadjuvant treatment, implying that S-DKK1 may serve as a useful biomarker for treatment monitoring. Multivariate analysis identified S-DKK1 as an independent prognostic marker with respect to overall survival in EC patients with a hazard ratio of 2.23. In conclusion, our data implicate a negative prognostic role of DKK1 with respect to the clinical outcome in EC patients. Further prospective studies should be conducted to implement S-DKK1 into the clinical routine for risk stratification and treatment monitoring. Full article

(This article belongs to the Special Issue Oesophageal Adenocarcinoma)

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12 pages, 2173 KiB

Open AccessArticle

Landscape of Biomarkers and Actionable Gene Alterations in Adenocarcinoma of GEJ and Stomach—A Real World Data Analysis

by Louisa Hempel, Julia Veloso de Oliveira, Andreas Gaumann, Valeria Milani, Katrin Schweneker, Kristina Schenck, Bastian Fleischmann, Patrick Philipp, Stefanie Mederle, Arun Garg, Armin Piehler, Beate Gandorfer, Cordula Schick, Axel Kleespies, Ludger Sellmann, Marius Bartels, Thorsten Oliver Goetze, Alexander Stein, Eray Goekkurt, Lucia Pfitzner, Sebastian Robert and Dirk Hempel Show full author list Hide full author list

Cancers 2021, 13(17), 4453; https://doi.org/10.3390/cancers13174453 - 03 Sep 2021

Cited by 2 | Viewed by 2124

Abstract

After several years of negative phase III trials in gastric and esophageal cancer, a significant breakthrough in the treatment of metastatic adenocarcinomas of the gastroesophageal junction (GEJ) and stomach (GC) is now becoming evident with the emerging of precision oncology and implementation of molecular targets in tumor treatment. In addition, new generation studies such as umbrella and basket trials are focused on these molecular targets, which makes an early molecular diagnosis based on IHC/ISH and NGS necessary. The required companion diagnostics of Her2neu overamplification or PD-L1 expression is based on immunohistochemistry (IHC) or additionally in situ hybridization (ISH) in case of an IHC Her2neu score of 2+. However, there are investigator-dependent differences in the assessment of Her2neu amplification and different PD-L1 scoring systems obtained by IHC/ISH. The use of high-throughput technologies such as next-generation sequencing (NGS) holds the potential to standardize the analysis and thus make them more comparable. In the presented study, real-world multigene sequencing data of 72 Caucasian patients diagnosed with metastatic adenocarcinomas of GEJ and stomach were analyzed. In the clinical companion diagnostics, we found ESCAT level I molecular targets in one-third of our patients, which directly determined the therapy. In addition, we found potential targets in 14/72 patients (19.4%) who potentially qualify for precision therapies in corresponding molecular studies. The study highlights the importance of comprehensive molecular profiling for precision treatment of GEJ/GC and indicates that a biomarker evaluation should be performed for all patients with metastatic adenocarcinomas before the initiation of first-line treatment and during second-line or subsequent treatment. Full article

(This article belongs to the Special Issue Oesophageal Adenocarcinoma)

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13 pages, 4602 KiB

Open AccessArticle

CT Body Composition of Sarcopenia and Sarcopenic Obesity: Predictors of Postoperative Complications and Survival in Patients with Locally Advanced Esophageal Adenocarcinoma

by Uli Fehrenbach, Tilo Wuensch, Pia Gabriel, Laura Segger, Takeru Yamaguchi, Timo Alexander Auer, Nick Lasse Beetz, Christian Denecke, Dino Kröll, Jonas Raakow, Sebastian Knitter, Sascha Chopra, Peter Thuss-Patience, Johann Pratschke, Bernd Hamm, Matthias Biebl and Dominik Geisel

Cancers 2021, 13(12), 2921; https://doi.org/10.3390/cancers13122921 - 11 Jun 2021

Cited by 34 | Viewed by 4514

Abstract

Background: To assess the impact of body composition imaging biomarkers in computed tomography (CT) on the perioperative morbidity and survival after surgery of patients with esophageal cancer (EC). Methods: Eighty-five patients who underwent esophagectomy for locally advanced EC after neoadjuvant therapy between 2014 and 2019 were retrospectively enrolled. Pre- and postoperative CT scans were used to assess the body composition imaging biomarkers (visceral (VAT) and subcutaneous adipose tissue (SAT) areas, psoas muscle area (PMA) and volume (PMV), total abdominal muscle area (TAMA)). Sarcopenia was defined as lumbar skeletal muscle index (LSMI) ≤38.5 cm²/m² in women and ≤52.4 cm²/m² in men. Patients with a body mass index (BMI) of ≥30 were considered obese. These imaging biomarkers were correlated with major complications, anastomotic leakage, postoperative pneumonia, duration of postoperative hospitalization, disease-free survival (DFS), and overall survival (OS). Results: Preoperatively, sarcopenia was identified in 58 patients (68.2%), and sarcopenic obesity was present in 7 patients (8.2%). Sarcopenic patients were found to have an elevated risk for the occurrence of major complications (OR: 2.587, p = 0.048) and prolonged hospitalization (32 d vs. 19 d, p = 0.040). Patients with sarcopenic obesity had a significantly higher risk for postoperative pneumonia (OR: 6.364 p = 0.018) and a longer postoperative hospital stay (71 d vs. 24 d, p = 0.021). Neither sarcopenia nor sarcopenic obesity was an independent risk factor for the occurrence of anastomotic leakage (p > 0.05). Low preoperative muscle biomarkers (PMA and PMV) and their decrease (ΔPMV and ΔTAMA) during the follow-up period significantly correlated with shorter DFS and OS (p = 0.005 to 0.048). Conclusion: CT body composition imaging biomarkers can identify high-risk patients with locally advanced esophageal cancer undergoing surgery. Sarcopenic patients have a higher risk of major complications, and patients with sarcopenic obesity are more prone to postoperative pneumonia. Sarcopenia and sarcopenic obesity are both subsequently associated with a prolonged hospitalization. Low preoperative muscle mass and its decrease during the postoperative follow-up are associated with lower DFS and OS. Full article

(This article belongs to the Special Issue Oesophageal Adenocarcinoma)

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15 pages, 5706 KiB

Open AccessArticle

Novel Histologic Categorization Based on Lauren Histotypes Conveys Prognostic Information for Gastroesophageal Junction Cancers—Analysis from a Large Single Center Cohort in Germany

by Rebekka Schirren, Alexander Novotny, Julia Slotta-Huspenina, Helmut Friess and Daniel Reim

Cancers 2021, 13(6), 1303; https://doi.org/10.3390/cancers13061303 - 15 Mar 2021

Cited by 1 | Viewed by 1501

Abstract

Adenocarcinoma of the gastroesophageal junction (AEG) ranks among the most common cancers in the Western world with increasing incidence. However, the prognostic influence and applicability of the Lauren classification was not examined in detail before. The purpose of this analysis was to analyze the oncologic outcomes of GE-junction cancer related to the Lauren histotype in a large single center cohort. Data from the prospectively documented database of the Klinikum Rechts der Isar (TUM School of Medicine) for patients undergoing curatively intended oncologic resection for GE-junction cancer between 1984 and 2018 were extracted. Univariate and multivariate regression analyses were performed to identify predictors for overall survival. Kaplan-Meier analyses were done to investigate the survival rates according to the Lauren histotype. After identification of two distinct histologic categories with prognostic implications, propensity score matching (PSM) was performed to balance for confounders and evaluate its oncologic outcomes retrospectively. In the time period indicated, 1710 patients were treated for GE-junction cancer. Exclusion criteria were: R2-resections (n = 134), metastatic disease (n = 296), 30-day mortality (n = 45), Siewert type I (n = 21), and missing/incomplete data (n = 61). Finally, 1153 patients were analyzed. In a multiple variable analysis, age, UICC-stage, all Lauren histotypes, R-stage, and postoperative complications were significant predictors of overall survival. Kaplan Meier analysis demonstrated significant survival differences between intestinal, diffuse, and mixed Lauren-histotypes (p = 0.001 and p = 0.029). Survival rates were comparable between non-classifiable and intestinal Lauren-types (p = 0.16) and between diffuse and mixed types (p = 0.56). When combining non-classifiable, well, and moderately differentiated Lauren-types and combining poorly differentiated intestinal, diffuse, and mixed types, two highly prognostic groups were identified (p < 0.0001). This was confirmed after PSM for possible confounders. The Lauren histotypes demonstrate highly prognostic value after oncologic resection of GE-junction cancer (Siewert type II and type III) in a single center Western patient cohort. A simplified histotype classification based on Lauren subtypes revealed a clear distinction of prognostic groups and should be considered for further evaluation. Full article

(This article belongs to the Special Issue Oesophageal Adenocarcinoma)

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Review

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13 pages, 607 KiB

Open AccessReview

Causal Link of Human Papillomavirus in Barrett Esophagus and Adenocarcinoma: Are We There Yet?

by Shanmugarajah Rajendra and Prateek Sharma

Cancers 2023, 15(3), 873; https://doi.org/10.3390/cancers15030873 - 31 Jan 2023

Viewed by 1837

Abstract

Esophageal cancer is a relatively common malignancy worldwide with a high mortality (5-year survival of <15%). Despite screening, surveillance, improved imaging and treatment, the exponential rise in OAC continues. The strongest risk factors for OAC are chronic heartburn and metaplastic transformation of the lower third of the esophagus (Barrett’s esophagus). The risk profile includes Caucasian race, male gender older age, obesity and smoking. Although the tumor risk in BO has been progressively revised downwards, the exponential rise in OAC remains unchecked. This paradox points to an unidentified missing link. Relatively recently, we provided the world’s initial data for a strong association of biologically relevant hr-HPV with BD and OAC. Since then, systematic reviews and meta-analysis have documented HPV DNA prevalence rates in OAC of between 13 to 35%. In this review, we provide some evidence for a probable causal relationship between hr-HPV and OAC. This is challenging given the multifactorial etiology and long latency. Increasingly, high-risk HPV (hr-HPV) is regarded as a risk factor for OAC. This discovery will aid identification of a sub-group of high-risk progressors to esophageal cancer by surveillance and the development of effective preventive strategies including vaccination. Full article

(This article belongs to the Special Issue Oesophageal Adenocarcinoma)

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15 pages, 873 KiB

Open AccessReview

Adequate Management of Postoperative Complications after Esophagectomy: A Cornerstone for a Positive Outcome

by Imad Kamaleddine, Alexander Hendricks, Magdalena Popova and Clemens Schafmayer

Cancers 2022, 14(22), 5556; https://doi.org/10.3390/cancers14225556 - 12 Nov 2022

Cited by 3 | Viewed by 2334

Abstract

Background: Esophagectomy for cancer is one of the most complex procedures in visceral surgery. Postoperative complications negatively affect the patient’s overall survival. They are not influenced by the histology type (adenocarcinoma (AC)/squamous cell carcinoma (SCC)), or the surgical approach (open, laparoscopic, or robotic-assisted). Among those dreadful complications are anastomotic leak (AL), esophago-respiratory fistula (ERF), and chylothorax (CT). Methods: In this review, we summarize the methods to avoid these complications, the diagnostic approach, and new therapeutic strategies. Results: In the last 20 years, both centralization of the medical care, and the development of endoscopy and radiology have positively influenced the management of postoperative complications. For the purpose of their prevention, perioperative measures have been applied. The treatment includes conservative, endoscopic, and surgical approaches. Conclusions: Post-esophagectomy complications are common. Prevention measures should be known. Early recognition and adequate treatment of these complications save lives and lead to better outcomes. Full article

(This article belongs to the Special Issue Oesophageal Adenocarcinoma)

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14 pages, 884 KiB

Open AccessReview

Tumor Microenvironment of Esophageal Cancer

by Lars M. Schiffmann, Patrick S. Plum, Hans F. Fuchs, Benjamin Babic, Christiane J. Bruns and Thomas Schmidt

Cancers 2021, 13(18), 4678; https://doi.org/10.3390/cancers13184678 - 18 Sep 2021

Cited by 14 | Viewed by 3712

Abstract

Esophageal cancer is among the top ten most deadly cancers worldwide with adenocarcinomas of the esophagus showing increasing incidences over the last years. The prognosis is determined by tumor stage at diagnosis and in locally advanced stages by response to (radio-)chemotherapy followed by radical surgery. Less than a third of patients with esophageal adenocarcinomas completely respond to neoadjuvant therapies which urgently asks for further strategies to improve these rates. Aiming at the tumor microenvironment with novel targeted therapies can be one strategy to achieve this goal. This review connects experimental, translational, and clinical findings on each component of the esophageal cancer tumor microenvironment involving tumor angiogenesis, tumor-infiltrating immune cells, such as macrophages, T-cells, myeloid-derived suppressor cells, and cancer-associated fibroblasts. The review evaluates the current state of already approved concepts and depicts novel potentially targetable pathways related to esophageal cancer tumor microenvironment. Full article

(This article belongs to the Special Issue Oesophageal Adenocarcinoma)

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18 pages, 326 KiB

Open AccessReview

Combined Therapy of Locally Advanced Oesophageal and Gastro–Oesophageal Junction Adenocarcinomas: State of the Art and Aspects of Predictive Factors

by Milan Vošmik, Jindřich Kopecký, Stanislav John, Ondřej Kubeček, Petr Lochman, Aml Mustafa Banni, Libor Hruška and Igor Sirák

Cancers 2021, 13(18), 4591; https://doi.org/10.3390/cancers13184591 - 13 Sep 2021

Viewed by 1876

Abstract

The following main treatment approaches are currently used in locally advanced adenocarcinomas of the oesophagus and gastrooesophageal junction (GOJ): preoperative chemoradiotherapy and surgery, and perioperative chemotherapy and surgery. While preoperative chemoradiotherapy is used primarily in oesophageal tumours, perioperative chemotherapy is the treatment of choice in Western countries for gastric cancer. The optimal treatment strategy for GOJ adenocarcinoma is still not clear. In comparison to other malignancies, biomarkers are used as predictive factors in distal oesophageal and GOJ adenocarcinomas in a very limited way, and moreover, only in metastatic stages (e.g., HER2 status, or microsatellite instability status). The aim of the article is to provide an overview of current treatment options in locally advanced adenocarcinomas of oesophagus and GOJ based on the latest evidence, including the possible potential of predictive biomarkers in optimizing treatment. Full article

(This article belongs to the Special Issue Oesophageal Adenocarcinoma)

Other

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23 pages, 514 KiB

Open AccessSystematic Review

Post-Neoadjuvant Surveillance and Surgery as Needed Compared with Post-Neoadjuvant Surgery on Principle in Multimodal Treatment for Esophageal Cancer: A Scoping Review

by Julian Hipp, Blin Nagavci, Claudia Schmoor, Joerg Meerpohl, Jens Hoeppner and Christine Schmucker

Cancers 2021, 13(3), 429; https://doi.org/10.3390/cancers13030429 - 23 Jan 2021

Cited by 14 | Viewed by 2963

Abstract

Background: A substantial fraction of patients with esophageal cancer show post-neoadjuvant pathological complete response (pCR). Principal esophagectomy after neoadjuvant treatment is the standard of care for all patients, although surveillance and surgery as needed in case of local recurrence may be a treatment alternative for patients with complete response (CR). Methods: We performed a scoping review to describe key characteristics of relevant clinical studies including adults with non-metastatic esophageal cancer receiving multimodal treatment. Until September 2020, relevant studies were identified through systematic searches in the bibliographic databases Medline, Web of Science, Cochrane Library, Science Direct, ClinicalTrials, the German study register, and the WHO registry platform. Results: In total, three completed randomized controlled trials (RCTs, with 468 participants), three planned/ongoing RCTs (with a planned sample size of 752 participants), one non-randomized controlled study (NRS, with 53 participants), ten retrospective cohort studies (with 2228 participants), and one survey on patients’ preferences (with 100 participants) were identified. All studies applied neoadjuvant chemoradiation protocols. None of the studies examined neoadjuvant chemotherapeutic protocols. Studies investigated patient populations with esophageal squamous cell carcinoma, adenocarcinoma, and mixed cohorts. Important outcomes reported were overall, disease-free and local recurrence-free survival. Limitations of the currently available study pool include heterogeneous chemoradiation protocols, a lack of modern neoadjuvant treatment protocols in RCTs, short follow-up times, the use of heterogeneous diagnostic methods, and different definitions of clinical CR. Conclusion: Although post-neoadjuvant surveillance and surgery as needed compared with post-neoadjuvant surgery on principle has been investigated within different study designs, the currently available results are based on a wide variation of diagnostic tools to identify patients with pCR, short follow-up times, small sample sizes, and variations in therapeutic procedures. A thoroughly planned RCT considering the limitations in the currently available literature will be of great importance to provide patients with CR with the best and less harmful treatment. Full article

(This article belongs to the Special Issue Oesophageal Adenocarcinoma)

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