Esophageal Cancer Treatment by Stage

Two different cancers share this organ's name. Squamous cell carcinoma arises from the lining. Adenocarcinoma arises from glandular change, usually in the lower esophagus, and is often linked to reflux and Barrett esophagus.

They are not treated the same, and the difference is measurable. In the CROSS trial, chemoradiation before surgery raised median overall survival in squamous cell carcinoma from 21.1 months to 81.6 months. In adenocarcinoma it moved from 27.1 months to 43.2 months. Both are gains. They are not the same size.

So the first thing to establish is which cell type this is. Location follows from it. Options follow from both.

Stage here comes from several tests, and NCI publishes how accurate each one is.

Endoscopic ultrasound stages tumor depth with 85% to 90% accuracy. CT manages 50% to 80%. For lymph nodes, endoscopic ultrasound reaches 70% to 80% and CT 50% to 70%. One retrospective series of ultrasound-guided fine-needle aspiration reported 93% sensitivity and 100% specificity for nodal staging.

PET adds a different thing. In 262 people with potentially resectable disease, PET found confirmed distant metastases in at least 4.8% after standard evaluation was already complete. Those are people whose whole plan changed.

Surgical staging can add more. An intergroup trial raised positive node detection from 41% to 56% using thoracoscopy and laparoscopy, with no major complications.

Depth is defined precisely at this end. Tis means high-grade dysplasia, with malignant cells still confined by the basement membrane. T1a means the tumor has reached the lamina propria or muscularis mucosae and no further.

NCI lists endoscopic approaches among the options here, alongside surgery. The trade-off is real. Endoscopic treatment preserves the esophagus. It also cannot assess lymph nodes, which is why depth matters so much at this stage.

For disease that has grown deeper or reached nodes, two established approaches exist. Until recently they had never been compared head to head.

The CROSS regimen is chemoradiation before surgery. It is weekly carboplatin with paclitaxel, both at low doses the team calculates, alongside a course of radiation given daily over about five weeks. The radiation dose and the number of sessions are planned individually. In the CROSS trial, 366 people were randomized against surgery alone. Median overall survival went from 24 months to 48.6 months.

FLOT is chemotherapy alone, given before and after surgery. It combines fluorouracil, leucovorin, oxaliplatin and docetaxel.

ESOPEC compared the two directly in 438 people with resectable esophageal adenocarcinoma. Three-year overall survival was 57.4% with FLOT and 50.7% with CROSS. Median overall survival was 66 months against 37 months. Pathological complete response was 16.7% against 10.1%. Death within 90 days of surgery was 3.1% against 5.6%.

One caveat belongs with that result. NCI notes that patients in the ESOPEC CROSS arm did not receive a year of adjuvant nivolumab, which is now standard after chemoradiation when disease remains.

Completion rates matter too. In the FLOT group, 89% finished the full course of chemotherapy planned before surgery. Only 53% finished the full course planned afterward.

Surgery does not end the decision. CheckMate 577 enrolled 794 people with R0 stage II or III disease who had already had neoadjuvant chemoradiation and still had residual disease in the specimen.

They received nivolumab by infusion for up to a year, on a schedule that lengthened partway through. Median disease-free survival was 22.4 months against 11.0 months with placebo. In squamous disease it was 29.7 months against 11.0. PD-L1 expression was not required for entry.

NCI adds a limit worth repeating. Overall survival data from that trial have not been published.

Here the two cell types diverge again. A checkpoint drug added to chemotherapy is a first-line option in both, but the trials that support it read out by PD-L1 level, so whether it applies to you depends on your own score rather than on the diagnosis alone.

Which of these applies to you turns on cell type, stage, PD-L1 result, fitness, organ function and what is currently approved where you are treated; the trial schedules below are evidence, not a plan.

For squamous cell carcinoma, CheckMate 648 randomized 970 people. Among those with PD-L1 expression of 1% or more, median overall survival was 15.4 months with nivolumab plus fluorouracil and cisplatin, 13.7 months with nivolumab plus ipilimumab, and 9.1 months with chemotherapy alone.

KEYNOTE-590 tested pembrolizumab added to fluorouracil and cisplatin, given in repeating cycles over a capped period. In squamous disease with a PD-L1 combined positive score of 10 or more, median overall survival was 13.9 months against 8.8 months.

That CPS number is worth asking for by value, not as a yes or no.

HER2 testing appears on many gastroesophageal reports, and its meaning depends on the setting.

NRG Oncology/RTOG-1010 screened 606 people and randomized 203 with HER2-positive esophageal adenocarcinoma to chemoradiation with or without trastuzumab before surgery. Median disease-free survival was 19.6 months against 14.2 months, with a hazard ratio of 0.99 and a P value of .97. There were five treatment-related deaths in the trastuzumab group and three in the other.

NCI's conclusion is unambiguous: trastuzumab has no role in the preoperative treatment of HER2-positive esophageal or gastroesophageal cancer. A separate phase II trial adding trastuzumab and pertuzumab to FLOT raised pathological complete response from 12% to 35%, but grade 3 or higher diarrhea rose from 5% to 41%, and the trial closed early.

More on how that result is worded is in what HER2 status means.

Systemic treatment takes weeks to work. A narrowed esophagus does not wait.

NCI names the recommended answer directly. Self-expandable metal stent positioning is the recommended method for palliation of dysphagia from esophageal cancer. Radiation can relieve it where the obstruction is partial. Intraluminal brachytherapy, photodynamic therapy, and Nd:YAG laser are also listed.

Raising a swallowing problem early keeps these options open and protects nutrition, which in turn decides what treatment is tolerable. More on the symptom is in difficulty swallowing, and background on the disease is in esophageal cancer and esophageal cancer types.

• Call 911 or go to an emergency department if you vomit blood, or you are gasping, choking, or cannot get words out. Do the same, without waiting for a call back, if your temperature hits 100.4°F (38°C) or higher while you are having chemotherapy or chemoradiation. CDC counts that as an emergency, because these regimens drop the white cells that fight infection.
• Call your care team the same day if your stools turn black or dark red, or nothing will go down at all after a stent is placed.
• Call your care team within a day or two if swallowing narrows again, it hurts in your chest or throat to swallow, you cough or choke while eating, or you keep losing weight.

• NCI PDQ — Esophageal Cancer Treatment (Health Professional Version)
• NCI PDQ — Esophageal Cancer Treatment (Patient Version)
• NHS — Oesophageal cancer: symptoms
• NCI — Infection and neutropenia during cancer treatment
• CDC — Watch out for fever