Esophageal Cancer Clinical Practice Guidelines (2019)

National Comprehensive Cancer Network (NCCN)

This is a quick summary of the guidelines without analysis or commentary. For more information, go directly to the guidelines by clicking the link in the reference.

August 01, 2019

The updated guidelines on esophageal cancer were released in July 2019 by the National Comprehensive Cancer Network (NCCN).[1]

Biomarker Testing

HER2 testing is recommended for all patients with esophageal or esophagogastric junction (EGJ) cancer at the time of diagnosis.

Microsatellite instability–high (MSI-H), deficient mismatch repair (dMMR), and programmed death ligand 1 (PD-L1) testing is recommended in all patients with esophageal or EGJ adenocarcinoma if metastatic disease is documented or suspected.

Principles of Surgery

Esophagectomy should be considered for all medically fit patients with resectable esophageal cancer (>5 cm from the cricopharyngeus).

Cervical or cervicothoracic esophageal cancers <5 cm from the cricopharyngeus should be treated with definitive chemoradiation.

Combined Modality Therapy

Preoperative chemoradiation is the preferred approach for localized resectable disease.

Perioperative chemotherapy or preoperative chemotherapy are alternative options for adenocarcinoma of the thoracic esophagus or EGJ.

Other treatment options include postoperative chemoradiation and postoperative chemotherapy.

Definitive chemoradiation should be reserved for patients with unresectable disease or those who decline surgery.

Systemic Therapy for Locally Advanced or Metastatic Disease

First-line therapy

First-line systemic therapy regimens with 2 cytotoxic drugs are preferred for treatment of advanced disease because of their lower toxicity.

Three-drug cytotoxic regimens should be reserved for medically fit patients with good performance status and access to frequent toxicity evaluation.

The preferred regimens for first-line systemic therapy include a fluoropyrimidine (fluorouracil or capecitabine) combined with either oxaliplatin or cisplatin.

In patients with HER2-positive metastatic adenocarcinoma, trastuzumab should be added to first-line chemotherapy (category 1 for combination with cisplatin and fluoropyrimidine).

Second-line and subsequent therapy

The selection of regimens for second-line or subsequent therapy depends on prior therapy and performance status.

Category 1 preferred options for second-line or subsequent therapy include single-agent docetaxel, paclitaxel, and irinotecan.

Pembrolizumab is a preferred second-line or subsequent therapy option for MSI-H/dMMR tumors; a second-line therapy option for esophageal cancers with PD-L1 expression levels (by combined positive score [CPS]) of ≥10 (category 2B); and a third-line or subsequent therapy option for esophageal and EGJ adenocarcinomas with PD-L1 expression levels by CPS of ≥1.

FOLFIRI is a preferred second-line treatment option if it was not used in first-line therapy.

Other recommended combined regimens for second-line therapy include irinotecan and cisplatin, and irinotecan and docetaxel (category 2B).

Targeted Therapies

Trastuzumab combined with mFOLFOX6 is an effective regimen with an acceptable safety profile and warrants further study in patients with HER2+ gastroesophageal cancers.

Ramucirumab, as a single agent or in combination with paclitaxel, and pembrolizumab (for MSI-H/dMMR tumors) are options for second-line or subsequent therapy for patients with metastatic disease.

For more information, see Esophageal Cancer. For more Clinical Practice Guidelines, please go to Guidelines.

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