Why Biomarker Testing Can’t Be an Afterthought in Upper GI Cancer

Biomarker status has a significant impact on treatment selection for unresectable advanced gastric cancer, and the increased number of biomarkers creates inconsistency between protocols across different oncology practices. In a Case-Based Roundtable event moderated by Ronan J. Kelly, MD, MBA, director of the Charles A. Sammons Cancer Center at Baylor University Medical Center in Dallas, Texas, oncologists considered a case patient with gastric adenocarcinoma and discussed their experiences with biomarker testing in this setting.

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CASE SUMMARY

• A 60-year-old man with abrupt 10-pound weight loss, dyspepsia, bloating after meals, and loss of appetite, and all symptoms worsening over the past 3 months
• Family history: father deceased age 50 (gastric cancer)​
• Medical history: overweight, hypertension​
• Esophagogastroduodenoscopy showed 2-cm protruding mass in the body of the stomach, without ulceration​
• Biopsy revealed poorly differentiated adenocarcinoma

DISCUSSION QUESTIONS

• What biomarkers do you consider when determining systemic therapy for this patient? For example,​ HER2​, PD-L1 expression level by combined positive score (CPS), mismatch repair/microsatellite instability status​, tumor mutational burden (TMB)​, NTRK gene fusion/mutation​, Epstein-Barr virus​, next-generation sequencing (NGS) and/or liquid biopsy​, Claudin 18.2, other​
• Do you do reflex testing (pathologist-initiated) with the initial pathology sample?​
• Discuss how reflex testing has impacted your practice and/or how you foresee its future role in your practice.

EVENT RECAP

One of the first substantive discussions of the evening centered on how and how consistently oncologists are ordering biomarker testing for patients with newly diagnosed metastatic gastric and gastroesophageal junction (GEJ) cancers. Kelly framed the conversation around a practical patient case: a 60-year-old man presenting with weight loss, dyspepsia, and a poorly differentiated adenocarcinoma of the stomach, prompting the group to consider which biomarkers should be standard workup before initiating systemic therapy.

Kelly laid out the full landscape of relevant markers along with the question of whether pathologist-initiated reflex testing is being incorporated into practice. The group's responses revealed a meaningful range of real-world approaches.

Manmeet Mangat, MD, noted that his practice routinely orders NGS for all patients with metastatic disease, and increasingly for earlier-stage diagnoses as well. Kelly acknowledged the value of that approach but was quick to point out an important limitation: several of the most clinically relevant markers in this disease—PD-L1 by CPS scoring, HER2 by immunohistochemistry or fluorescence in situ hybridization, and Claudin 18.2 expression—cannot be reliably captured by NGS alone. These require immunohistochemistry (IHC) staining on tissue slides sent to pathology, and there is a real risk that clinicians who send out NGS and wait for results may be missing key information needed to personalize first-line therapy.

Deepak Bhamidipati, MD, who practices in Tennessee, offered a nuance from personal experience: some commercial platforms, such as Tempus and Caris, do include IHC add-ons for HER2 and Claudin 18.2 by default, which may be what many colleagues think when they say their NGS covers everything. Even so, he acknowledged that pathologists without a strong oncology focus may not automatically reflexively test for all relevant markers, making physician-initiated ordering an important backstop.

Rashad Khan, MD, practicing in East Texas, described a situation that is likely familiar to many community oncologists: his pathology department waits for clinician-directed NGS orders rather than initiating reflex testing, which means Claudin 18.2 and other IHC-based markers may not be returned unless specifically requested.

Kelly underscored the practical implication here. NGS turnaround can run 1 to 2 weeks depending on the laboratory and location, but IHC results should be available within a few days, a meaningful distinction when patients are symptomatic and treatment decisions are time-sensitive. He referenced a recent conference where colleagues raised similar concerns about testing gaps in the community, suggesting this is not a localized problem.

Rozina Chowdhery, MD, offered a more encouraging picture from her practice, which operates within an affiliation with a large academic center: all IHC and NGS are performed in-house as part of a standardized panel for gastric and GEJ cancers. The takeaway from the discussion as a whole was that while awareness of the required biomarker landscape has grown, the consistency of testing, particularly for Claudin 18.2, remains variable, and reflex testing protocols have not been universally adopted. For the group, this reinforced why physician education on the complete testing picture remains essential as treatment algorithms become increasingly biomarker-driven.

CASE UPDATE

• Molecular testing: HER2/neu (-); mismatch repair proficient/microsatellite stable; PD-L1 CPS: 5; Claudin18.2 < 75%​
• CT scan of abdomen and chest revealed a gastric polypoid mass and thickening; no ascites; 2 lesions in the left lung lower lobe​
• Lung biopsy confirmed metastatic adenocarcinoma consistent with gastric primary ​
• Diagnosis: stage IV gastric adenocarcinoma

How would you vote?

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_{DISCLOSURES: Kelly had no known relevant disclosures.}