Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: Systematic review with meta-analysis combining individual patient and aggregate data☆
Introduction
Adenocarcinoma of the stomach, gastroesophageal junction and oesophagus (‘gastroesophageal adenocarcinoma’) ranks among the most common cancers.1, 2, 3, 4 Radical surgery is the most effective curative treatment modality. Despite improved surgical techniques and perioperative management,1, 4 five-year survival after resection is only 20–30% in patients with locoregionally advanced disease.5, 6 These poor survival rates provide a strong rationale for the design of new treatment modalities. Preoperative chemotherapy, defined as chemotherapy before and, optionally, after surgery, has been tested in randomised controlled trials (RCTs).7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 Results have been conflicting and inconclusive.
Systematic reviews and meta-analyses to date, that have summarised the evidence have either combined oesophageal squamous cell carcinoma and adenocarcinoma or failed to include all three tumour sites of GE adenocarcinoma.21, 22, 23, 24 Moreover, the analyses have been based on aggregate data, limiting their ability to sufficiently assess which patient and tumour characteristics might alter the treatment effect of preoperative chemotherapy. Therefore, we performed a new systematic comparison, based largely on individual patient data, of preoperative chemotherapy versus surgery alone for patients with locoregional resectable adenocarcinoma of the stomach, gastroesophageal junction and oesophagus.
Section snippets
Methods
The study was carried out according to Cochrane methodology and the previously published protocol.25 The full publication in the Cochrane Library provides a more detailed description of the methods.26
Identification of studies
Search results are displayed in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram (Fig. 1). Out of 7099 screened records, fourteen RCTs (total patients n = 3041) met our inclusion criteria (web extra table).7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 Five RCTs (n = 1657) included both patients with oesophageal adenocarcinoma and squamous cell carcinoma,7, 8, 12, 15, 16 and comprised n = 1045 patients with adenocarcinoma. The total number of patients with
Discussion
This meta-analysis uses IPD to assess benefits of preoperative chemotherapy for gastroesophageal adenocarcinoma. Unlike earlier meta-analyses,21, 22, 23, 24 we included all tumour locations: oesophagus, gastroesophageal junction and stomach. Our access to IPDallowed us to selectively include patients with oesophageal adenocarcinoma from trials with mixed histology. Conversely, we were able to exclude patients with squamous cell carcinoma, which has a different biological behaviour.37 Our most
Conflict of interest statement
None declared.
Acknowledgements
This work was supported by the German Federal Ministry of Education and Research (Grant number 01KG 0807). The funding source had no role in the study design; collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. We thank the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group for assistance with the literature search and project management. We thank Jean-Pierre Pignon (Meta-Analysis Unit, Institut
References (46)
- et al.
Gastric cancer: global pattern of the disease and an overview of environmental risk factors
Best Pract Res Clin Gastroenterol
(2006) - et al.
Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial
Lancet Oncol
(2005) - et al.
Neo-adjuvant chemotherapy for operable gastric cancer: long term results of the Dutch randomised FAMTX trial
Eur J Surg Oncol
(2004) - et al.
Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis
Lancet Oncol
(2011) - et al.
Individual patient data-based meta-analysis assessing the effect of preoperative chemo-radiotherapy in resectable oesophageal carcinoma
Int J Radiat Oncol Biol Phys
(2008) - et al.
The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials
J Clin Epidemiol
(1997) - et al.
A critical review of methods for the assessment of patient-level interactions in individual participant data meta-analysis of randomized trials, and guidance for practitioners
J Clin Epidemiol
(2011) - et al.
The impact of primary tumour origins in patients with advanced oesophageal, oesophago-gastric junction and gastric adenocarcinoma – individual patient data from 1775 patients in four randomised controlled trials
Ann Oncol
(2009) - et al.
Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial
Eur J Cancer
(2011) Adenocarcinoma of the esophagus and cardia: a review of the disease and its treatment
Ann Surg Oncol
(2006)
Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008
Int J Cancer
Updates on esophageal and gastric cancers
World J Gastroenterol
Curative resection for esophageal adenocarcinoma: analysis of 100 en bloc esophagectomies
Ann Surg
Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study
Ann Surg
Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer
J Clin Oncol
Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer
N Engl J Med
Treatment out come of neoadjuvant chemotherapy for Bormann’s type IV gastric cancer
Chin J Cancer Prev Treat
Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer
J Clin Oncol
Long-term outcome of preoperative chemotherapy with 5′-deoxy-5-fluorouridine (5′-DFUR) for gastric cancer
Gan To Kagaku Ryoho
Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954
J Clin Oncol
Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781
J Clin Oncol
Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma
J Clin Oncol
A comparison of multimodal therapy and surgery for esophageal adenocarcinoma
N Engl J Med
Cited by (146)
Prospective evaluation of MR-TRG (Tumor Regression Grade) in esophageal cancer after neo-adjuvant therapy: Preliminary results
2024, European Journal of RadiologyOesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
2022, Annals of OncologyEffects of neoadjuvant chemotherapy vs chemoradiotherapy in the treatment of esophageal adenocarcinoma: A systematic review and meta-analysis
2024, World Journal of GastroenterologyA Systemic Review on Photodynamic Therapy: Emerging Technology with Healing Process
2024, Current Cancer Therapy Reviews