HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma

This clinical practice guideline “HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma Update” will address appropriate testing of human epidermal growth factor receptor 2 (HER2) status in patients with advanced gastroesophageal adenocarcinoma (GEA). The key questions that the guideline development panel of experts addressed were:

1. In specimens from patients with advanced GEA, do HER2 test results from other sites or specimens (resection specimens, tissues from metastatic sites, FNA/cytology specimens from primary or metastatic tumors, liquid biopsies) yield concordant results when compared to primary biopsy specimens?
2. In specimens from patients with advanced GEA, how do the test characteristics of genomic testing (NGS/PCR across tissue-based and blood-based platforms) compare with traditional HER2 assessment methodologies (IHC with different antibodies, ISH with various probe platforms)?
3. In patients with advanced HER2-positive GEA being considered for subsequent therapy after disease progression, does repeat HER2 testing inform further treatment decisions compared to not repeating testing?
4. In untreated patients with advanced HER2-positive GEA, is PD-L1 testing recommended as a tool for clinical decision making compared to not testing?

Ten recommendations are included to address opportunities for improving patient outcomes. The updated guideline includes four new or updated recommendations and reinforces six existing recommendations as good practice statements to reflect current evidence and practice clarity.

• Guideline status: Open Comment Period
• Published online ahead of print: November 14, 2016
• Originally published: December 2016
• Collaborators: American Society for Clinical Pathology and American Society of Clinical Oncology

All stakeholders—pathologists, gastroenterologists, oncologists, histotechnologists, hospital or laboratory managers, and patient advocacy group representatives—are encouraged to review and submit feedback on the draft recommendations from May 28 to June 18, 2025.

Review the following resources to provide your feedback:

• Data extraction references
• Draft recommendations
• Grades for certainty of evidence and strength of recommendations
• Expert panel disclosures of interest report
   

The information, data, and draft recommendations provided by the College of American Pathologists are presented for informational and public feedback purposes only. The draft recommendations and supporting documents will be removed on June 25, 2025. The draft recommendations along with the public comments received and completed evidence review will be reassessed by the expert panel in order to formulate the final recommendations. These draft materials should not be stored, adapted, or redistributed in any manner.

Please note: Comments are not posted automatically. All comments will be posted on a weekly basis beginning June 4, 2025. Following the open comment period, the guideline authors will consider all feedback to finalize the recommendations. The final recommendations will be formally published as a guideline in Archives of Pathology & Laboratory Medicine. The CAP Pathology and Laboratory Quality Center for Evidence-based Guidelines (Center) develops recommendations related to the practice of pathology and laboratory medicine. Through this work, we and our members continually improve the quality of diagnostic medicine and patient outcomes. For questions, please contact CENTER@CAP.ORG.