Adjuvant and neoadjuvant treatment of gastric cancer
- Craig Earle, MD, MSc, FRCPC
Craig Earle, MD, MSc, FRCPC
- Director, Health Services Research Program
- Cancer Care Center and the Ontario Institute for Cancer Research
- Harvey Mamon, MD, PhD
Harvey Mamon, MD, PhD
- Associate Professor of Radiation Oncology
- Harvard Medical School
- Section Editors
- Richard M Goldberg, MD
Richard M Goldberg, MD
- Section Editor — Gastrointestinal Cancer
- Director of the West Virginia University Cancer Institute and the Mary Babb Randolph Cancer Center
- Professor of Medicine
- Laurence S. & Jean J. DeLynn Chair of Oncology
- Christopher G Willett, MD
Christopher G Willett, MD
- Section Editor — Radiation Therapy
- Duke University Medical School
The incidence of gastric cancer has been declining steadily since the 1930s, yet it remains a major cause of cancer death in the United States . The high mortality rate reflects the prevalence of advanced disease at presentation . In population-based series of Western populations, the five-year survival rate for patients with completely resected stage I gastric cancer is approximately 70 to 75 percent, while it drops to 35 percent or less for stage II disease and beyond (table 1) . These sobering results have spawned efforts to improve the treatment results for this group of patients using adjuvant (postoperative) or neoadjuvant (preoperative) therapies. (See "Surgical management of invasive gastric cancer", section on 'Prognosis'.)
The positive impact of such therapies on survival in patients with resected gastric cancer has become clearer over time, although there is no consensus as to the best approach. In many parts of the world, chemotherapy alone (either following surgery or combined preoperative and postoperative administration, as in the multinational MAGIC trial ) is the preferred treatment strategy. On the other hand, a large American Intergroup trial (INT0116) demonstrating a significant survival benefit for chemoradiotherapy after complete resection resulted in the adoption of this strategy in the United States, despite concerns that inadequate surgical staging (particularly the extent of lymphadenectomy) may have led to an overestimation of benefit . The issues surrounding extent of lymph node dissection in gastric cancer are discussed in detail elsewhere. (See "Surgical management of invasive gastric cancer", section on 'Extent of lymph node dissection'.)
Another controversial issue is the management of cancers arising at the esophagogastric junction (EGJ). The classification and management of these tumors have evolved over time. In the 2010 edition of the tumor, node, metastasis (TNM) staging manual, tumors arising at the EGJ or in the cardia of the stomach (figure 1) within 5 cm of the EGJ that extend into the EGJ or esophagus (the so-called Siewert III EGJ tumors ) were staged and treated as esophageal (table 2) rather than stomach cancers . However, tumors that arise beyond 5 cm of the EGJ, or are within 5 cm of the EGJ but without extension to the esophagus or EGJ are still classified and treated as gastric cancers. In the most recent eighth edition staging classification from 2017 , tumors involving the EGJ with a tumor epicenter no more than 2 cm into the proximal stomach are staged as esophageal cancers, while EGJ tumors with their epicenter located more than 2 cm into the proximal stomach are staged as stomach cancers, as are all cardia cancers not involving the EGJ. (See "Diagnosis and staging of esophageal cancer", section on 'TNM staging criteria' and "Clinical features, diagnosis, and staging of gastric cancer", section on 'TNM staging criteria'.)
This topic review will focus on adjuvant and neoadjuvant therapies for noncardia gastric cancer. The epidemiology, staging, and surgical treatment of gastric cancers and multimodality approaches for treatment of esophageal and EGJ tumors are covered separately. (See "Epidemiology of gastric cancer" and "Clinical features, diagnosis, and staging of gastric cancer" and "Surgical management of invasive gastric cancer" and "Radiation therapy, chemoradiotherapy, neoadjuvant approaches, and postoperative adjuvant therapy for localized cancers of the esophagus" and "Multimodality approaches to potentially resectable esophagogastric junction and gastric cardia adenocarcinomas".)
OVERVIEW OF THE THERAPEUTIC APPROACH
●Complete surgical resection is a prerequisite for cure of gastric cancer. However, the poor long-term survival rates after surgery alone for patients with locally advanced gastric and esophagogastric junction (EGJ) cancer have led to the exploration of a variety of adjuvant (postoperative) and neoadjuvant (preoperative) treatment strategies incorporating chemotherapy with or without radiation therapy (RT). The survival benefit from combined modality therapy as compared with surgery alone has become clearer over time.
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- OVERVIEW OF THE THERAPEUTIC APPROACH
- PATIENTS WHO HAVE ALREADY UNDERGONE POTENTIALLY CURATIVE RESECTION
- Adjuvant chemoradiotherapy
- - Intergroup 0116
- - CALGB 80101
- - ARTIST trial
- Adjuvant chemotherapy
- - Benefits
- - Choice of regimen
- Japanese S-1 trial
- CLASSIC trial
- Chemotherapy versus chemoradiotherapy
- Timing of adjuvant therapy
- Patient selection for adjuvant therapy
- PATIENTS WITH POTENTIALLY RESECTABLE DISEASE NOT YET RESECTED
- Neoadjuvant/perioperative chemotherapy
- - MAGIC trial
- - French FNLCC/FFCD trial
- - EORTC trial 40954
- - Meta-analysis
- - Choice of regimen and patient selection
- Neoadjuvant chemoradiotherapy
- Management of poor responders
- INITIALLY LOCALLY UNRESECTABLE NONMETASTATIC DISEASE
- ONGOING RESEARCH
- POSTTREATMENT CANCER SURVEILLANCE
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS