Diagnostic Workup for Stage 4 GEJ Adenocarcinoma

Manish A. Shah, MD:The appropriate staging for gastric and GEJ cancers begins with a physical examination and basic blood work. You need an endoscopy to establish the mass and the upper GI tract and to get tissue to make a diagnosis. You need a CAT scan to evaluate the extent of the disease. And that’s actually my typical starting pattern: an endoscopy and CAT scan. If the CAT scan is negative and it’s not obvious on the CAT scan, if there’s no disease or gastric wall thickening, then I would proceed with an endoscopic ultrasound because that can help differentiate early-stage versus locally advanced disease. If patients have early-stage disease, then often you might be able to go straight to surgery. If it’s locally advanced, you would consider perioperative therapy. But if the CAT scan shows metastatic disease, then I often do perform a biopsy to confirm this disease, primarily because this diagnosis of metastatic gastric cancer is life changing. It’s a terminal illness, unfortunately.

For patients who don’t have metastatic disease, we often perform a laparoscopy because occult metastatic disease and peritoneum happens in about 30% of patients. So, patients with locally advanced disease, based on imaging and endoscopic ultrasound, should have a laparoscopy prior to embarking on treatment for locally advanced disease.

Molecular testing is evolving in gastric and GE junction cancers. Just 5 years ago was the first time that we actually got a targeted agent approved, and that was trastuzumab for HER2-positive disease. Since then, we have 2 additional targeted agents that are approved but require 2 additional testings. So, the additional testing that should be done includes PD-L1 testing, for which—if you’re positive—in the third-line setting you can receive pembrolizumab. And mismatch repair deficient testing, which is for pembrolizumab in the second-line setting for tumors that are mismatch repair deficient.

So, our standard panel does include those 3. We do test for HER2 overexpression by IHC or FISH. We test for mismatch repair deficiency, and we also test for PD-L1 expression based on the combined positive score. Most places have a panel, and so do we at Weill Cornell. And so, this is a pretty comprehensive panel. It looks at other features likeRASmutations orCDH1orPIK3CA, things like that. But right now, they don’t have clinical significance, at least in gastric and GE junction cancers.

Transcript edited for clarity.

A 54-Year-Old Man With Stage IV Gastroesophageal Junction Cancer

January 2018

• A 54-year-old man presented to his PCP complaining of loss of appetite, indigestion, and dysphagia lasting approximately 4 months and subsequent 12-lb weight loss
• PE: patient was pale-appearing; abdominal auscultation
• Notable laboratory findings:
  • HB 10.8 g/dL
  • LFT WNL
  • CEA, 18.4 ng/mL
• Upper GI endoscopy with endoscopic ultrasound showed a hypoechoic mass, approximately 3.3 cm, located in the gastric cardia and extending to the gastroesophageal junction, infiltrating the gastric wall into the subserosal mucosa
• Biopsy results confirmed poorly differentiated gastric adenocarcinoma
  • Molecular testing; HER2(-), MSI-stable, PD-L1 expression 0%
• CT of chest, abdomen, and pelvis indicated liver mets confirmed
• Staging; GEJ adenocarcinoma T4bN0M1, unresectable, Siewert II
• PS; ECOG 0
• After multidisciplinary assessment, the patient was started on FOLFOX
• Three-month follow-up
  • Imaging showed a partial response to systemic therapy
  • Patient complained of mild neuropathy; oxaliplatin was discontinued after 4 cycles of chemotherapy

July 2018

• Patient reports increasing fatigue
• CT imaging at 6 months shows metastatic spread to multiple subcarinal and right hilar lymph nodes; increased size in two of the liver lesions
• PS; ECOG 1
• Patient is motivated to try another systemic therapy
• The patient is planned to start therapy with paclitaxel/ramucirumab