The 4th St. Gallen EORTC Gastrointestinal Cancer Conference: Controversial issues in the multimodal primary treatment of gastric, junctional and oesophageal adenocarcinoma

doi:10.1016/j.ejca.2019.01.106

European Journal of Cancer

Volume 112, May 2019, Pages 1-8

https://doi.org/10.1016/j.ejca.2019.01.106 Get rights and content

Highlights

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Summary report of the expert consensus discussion and vote focussed on the primary treatment of gastric and gastro-oesophageal adenocarcinoma.
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Expert consensus.
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EUS needed in AEG II/III.
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Laparoscopy in all gastric cancers and AEG II/III.
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FLOT regimen standard in gastric cancer.

Abstract

Multimodal primary treatment of localised adenocarcinoma of the stomach, the oesophagus and the oesophagogastric junction (AEG) was reviewed by a multidisciplinary expert panel in a moderated consensus session. Here, we report the key points of the discussion and the resulting recommendations. The exact definition of the tumour location and extent by white light endoscopy in conjunction with computed tomography scans is the backbone for any treatment decision. Their value is limited with respect to the infiltration depth, lymph node involvement and peritoneal involvement. Additional endoscopic ultrasound was recommended mainly for tumours of the lower oesophagogastric junction (i.e. AEG type II and III according to Siewert) and in early cancers before endoscopic resection. Laparoscopy to diagnose peritoneal involvement was thought to be necessary before the start of neoadjuvant treatment in all gastric cancers and in AEG type II and III. In general, perioperative multimodal treatment was suggested for all locally advanced oesophageal tumours and for gastric cancers with a clinical stage above T1N0. There was consensus that the combination of fluorouracil, folinic acid, oxaliplatin and docetaxel is now a new standard chemotherapy (CTx) regimen for fit patients. In contrast, the optimal choice of perioperative CTx versus neoadjuvant radiochemotherapy (neoRCTx), especially for AEG, was identified as an open question. Expert treatment recommendations depend on the tumour location, biology, the risk of incomplete (R1) resection, response to treatment, local or systemic recurrence risks, the predicted perioperative morbidity and patients' comorbidities. In summary, any treatment decision requires an interdisciplinary discussion in a comprehensive multidisciplinary setting.

Introduction

The topic of the 4th St. Gallen EORTC Gastrointestinal Cancer Conference 2018 was the primary approach to patients with potentially curable adenocarcinoma of the stomach, the gastro-oesophageal junction or the oesophagus, three anatomically defined tumour locations with distinct, although overlapping, molecular features and treatment strategies [1]. Differences in histopathology can be used to distinguish between intestinal-type gastric cancer and diffuse type according to the Lauren classification. The pathogenesis of intestinal-type gastric cancer and oesophageal adenocarcinoma is thought to follow a metaplasia–dysplasia–carcinoma sequence with identifiable premalignant conditions, namely, atrophy in the stomach and Barrett's metaplasia in the distal oesophagus [2].

More recently, comprehensive genomic characterisation has identified four molecular subtypes of gastric cancer: (i) tumours positive for Epstein–Barr virus, (ii) microsatellite unstable tumours, (iii) genomically stable tumours and (iv) tumours with chromosomal instability (CIN) [3]. Oesophageal adenocarcinoma commonly exhibits CIN, which makes its molecular background mechanism comparable to CIN-type gastric cancer [4].

About 2% of gastric cancers are associated with familial cancer syndromes: (i) hereditary diffuse gastric cancer, (ii) gastric adenocarcinoma and proximal polyposis of the stomach and (iii) familial intestinal gastric cancer [5], [6] and also the Lynch syndrome. These may need more extensive surgical approaches than those recommended for sporadic cancers [7].

A multidisciplinary faculty of specialised surgeons, medical and radiation oncologists, pathologists, radiologists and gastroenterologists reviewed the current treatment recommendations in a panel session based on a moderated consensus process. The main focus was on controversial issues that could not be easily resolved through the study of published evidence and guidelines. As in the St. Gallen Breast Cancer Conferences, the panel was asked to discuss the scientific evidence, contribute their personal and centre experiences and finally vote on recommendations developed from a precirculated set of questions. As an introductory question, the panel was asked if it is still appropriate to differentiate between patients with gastric and gastro-oesophageal cancer with respect to multimodal treatment decisions. The vast majority (89% or 16/18 including one abstention) of the panel members voted ‘yes’ on this issue. Hence, we have summarised the key discussion points of the panel members for gastric cancer and adenocarcinoma of the gastro-oesophageal junction or the oesophagus (AEG according to Siewert) [8] separately.

Section snippets

Methods

In preparation for the panel session held on March 17, 2018, existing guidelines were used to identify areas of uncertainty to define the topics for debate [9], [10], [11], [12], [13], [14], [15]. Topics and the resulting questions were circulated among panel members 3 weeks before the meeting. Seventy-seven questions were retained for the panel discussion. During the session, which was moderated by J.Z. and M.L., the panel members were asked to assess and comment on optimal care based on

Staging

Routine staging of gastric cancer includes white light endoscopy with biopsies taken for histopathological diagnosis and cross-sectional radiologic imaging of the thorax and abdomen.

The minimum number of biopsies needed for optimal evaluation was recommended by the panel to be at least six (72% of the panellists) or eight (17%), mainly because gastric cancers display a highly variable growth pattern with intratumoural heterogeneity and because diagnosis may be missed [16], [17]. At least five

Staging

Routine staging of AEG includes white light endoscopy and cross-sectional radiologic imaging of the thorax and abdomen. In selected cases, chromoendoscopy can help to define the longitudinal extent of the tumours with the aim to classify them as AEG type I (in the distal oesophagus), type II (cardia or gastro-oesophageal junction) or type III (subcardial gastric cancer) according to Siewert [8], [14].

EUS in addition to thoracic CT was recommended for all patients by most experts (75%), the

Conflict of interest statement

Manfred Lutz received grants or research support from Celgene and Shire and honoraria or consultation fees from Eli Lilly and Falk Foundation. John Zalcberg received grants or research supports from Specialized Therapeutics and Shire and honoraria or consultation fees from Pfizer, Amgen and MSD. Arnaud Roth received honoraria or consultation fees from Roche, Bayer, BMS, Celgene, Amgen and Merck. William Allum received honoraria or consultation fees from Eli Lilly, Nestle and Taiho and is a

Acknowledgements

This meeting was made possible through the generous financial support of St. Gallen Oncology Conferences. The authors wish to thank Hans-Jörg Senn and Agnes Glaus for their expertise as well as Judith Eberhardt and Fabienne Hevi for the excellent operational management of the conference.

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ReviewThe 4th St. Gallen EORTC Gastrointestinal Cancer Conference: Controversial issues in the multimodal primary treatment of gastric, junctional and oesophageal adenocarcinoma

Highlights

Abstract

Introduction

Section snippets

Methods

Staging

Staging

Conflict of interest statement

Acknowledgements

Crit Rev Oncol Hematol

Lancet Oncol

Am J Hum Genet

Ann Oncol

Eur J Surg Oncol

Eur J Cancer

Ann Oncol

Eur J Surg Oncol

Lancet Oncol

Ann Oncol

Ann Oncol

Lancet Oncol

Gastric adenocarcinoma

Nat Rev Dis Primers

Comprehensive molecular characterization of gastric adenocarcinoma

Nature

Integrated genomic characterization of oesophageal carcinoma

Nature

Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers

J Med Genet

Review
The 4th St. Gallen EORTC Gastrointestinal Cancer Conference: Controversial issues in the multimodal primary treatment of gastric, junctional and oesophageal adenocarcinoma