Esophageal and EGJ Cancers

Work up for staging:

• CT CAP with IV and oral contrast

• Endoscopic Ultrasound

• Bronchoscopy for tumors at/above the carina to rule out fistula

• Upper GI endoscopy/biopsy

• Consider staging laparoscopy: Best test to assess peritoneal metastases (mostly seen in signet ring histology).

  • At least 15 LNs need to be removed during surgery

Staging:

T1a: Tumor invades the lamina propria or muscularis mucosae

T1b: Tumor invades the submucosa

T2: Tumor invades the muscularis propria

T3: Tumor invades the adventitia

T4: Tumor invades the adjacent structures

Pathology:

• SCC: usually in the upper part of esophagus

  • Associated with tobacco use, EtOH use, achalasia, lye ingestion, plummer-vinson syndrome

• Adenocarcinoma: usually in the lower part of the esophagus/GE Junction

  • Associated with Barrett's esophagus

  • If there is high grade dysplasia or Tis lesions: 60% risk of developing invasive cancer

    • Consider endoscopic resection and/or ablation, or even esophagectomy

    • Low grade dysplasia risk to become invasive is much lower

    • Can do anti reflux therapy followed by EGD in 6-12 months

    
    

Treatment:

Localized/ Locally Advanced Resectable:

• Tis or T1a:

  • Endoscopic Submucosal Dissection (ESD) or esophagectomy

• T1b:

  • Esophagectomy

• T2N0 (if low risk, <3 cm, well diff, not located in cervical esophagus):

  • Esophagectomy

• T2N0 (if high risk, LVI, >3 cm, poorly diff, located in cervical esophagus) or anyTN+:

  • Neoadjuvant chemoRT (Carbo/taxol) → Surgery (CROSS trial)

  • Perioperative FLOT → Surgery (ESOPEC Trial)

  • Perioperative FLOT + durvalumab → Surgery (Matternhorn trial)

  • Definitive chemoRT:

    • Those who decline surgery

    • Preferred for cervical esophagus

  • Consider IO if MSI-H/dMMR

    • Any patient who receives neoadjuvant chemoRT with residual pathologic disease should receive adjuvant Nivolumab x1 year (Checkmate-577)

Metastatic Disease/Locally Advanced Unresectable:

• If squamous cell carcinoma:

  • First line:

    • Chemoimmunotherapy is preferred independent of PD-L1 CPS:

      • FOLFOX (or CAPEOX) + Nivolumab

      • FOLFOX (or CAPEOX) + Pembrolizumab

      • FOLFOX (or CAPEOX) + tislelizumab

    • If IO is contraindicated:

      • FOLFOX (or CAPEOX)

      • Carboplatin (or Cisplatin) +/- Taxol

    • If MSI-high/dMMR (independent of PD-L1 status):

      • Pembrolizumab

      • Dostarlimab

      • Nivolumab + Ipilimumab

    • If NTRK gene fusion positive:

      • Entrectinib

      • Larotrectinib

      • Repotrectinib:

  • Subsequent line:

    • Nivolumab

    • Docetaxel/ Paclitaxel

    • Irinotecan +/- 5FU

    • Tislelizumab-jsgr

    • Dabrafenib/Trametinib (BRAF V600E mutated)

    • Selpercatinib (RET positive)

• If Adenocarcinoma:

  • HER2 positive:

    • FOLFOX (or CAPEOX) + Trastuzumab +/- Pembro (based on PDL1 CPS)

  • HER2 negative:

    • If PDL1 CPS >1:

      • FOLFOX (or CAPEOX) + Nivolumab

      • FOLFOX (or CAPEOX) + Pembrolizumab

      • FOLFOX (or CAPEOX) + tislelizumab

    • If IO is contraindicated or PD-L1 CPS 0:

      • FOLFOX (or CAPEOX)

    • If CLDN 18.2 positive:

      • FOLFOX (or CAPEOX) + zolbetuximab

    • If MSI-high/dMMR (independent of PD-L1 status):

      • Pembrolizumab

      • Dostarlimab

      • Nivolumab + Ipilimumab

    • If NTRK gene fusion positive:

      • Entrectinib

      • Larotrectinib

      • Repotrectinib:

  • Subsequent line:

    • Ramucirumab + Paclitaxel

    • Enhertu for HER2+

    • Docetaxel/ Paclitaxel

    • Irinotecan +/- 5FU

    • Dabrafenib/ Trametinib (BRAF V600E mutated)

    • Selpercatinib (RET positive)

    • Lonsurf (trifluridine/Tipiracil): 3rd line