Esophageal cancer

Increasing difficulty swallowing, painful swallowing and unintended weight loss deserve investigation. Reflux or indigestion can have other causes, but persistent changes should not be assumed to be ordinary reflux. Endoscopy with biopsy confirms the histological diagnosis.

Squamous carcinoma is associated with exposures including tobacco and alcohol; adenocarcinoma is associated with reflux and Barrett’s esophagus. These associations do not identify an individual’s cause. Ask for the pathology type and the location measured from the incisors and relative to the gastroesophageal junction.

CT evaluates regional and distant disease; endoscopic ultrasound can assess wall depth and nearby nodes when useful and technically feasible. PET-CT can identify otherwise unsuspected spread in a potentially curative work-up. Selected upper or middle tumors may need airway assessment. Tests should answer whether the intended treatment remains appropriate.

Resectability describes whether the tumor can be removed; operability describes whether a person can tolerate the operation. Heart and lung function, frailty, weight loss and nutrition affect that judgment. Gastroesophageal-junction tumors need consistent site and staging definitions rather than switching between a gastric and esophageal label to fit a drug.

Some superficial cancers can be removed endoscopically. The removed specimen then establishes depth, differentiation, lymphovascular invasion and margin status. These determine whether endoscopic treatment was adequate or whether nodal-risk treatment is still needed. A lesion looking small does not by itself establish that local removal is curative.

For fit patients with resectable locally advanced esophageal adenocarcinoma, the ESOPEC randomized trial favored perioperative FLOT chemotherapy plus surgery over preoperative CROSS chemoradiation plus surgery. This supports a major role for FLOT in that population; it does not prove the same choice for squamous carcinoma or every person unable to tolerate FLOT.

Squamous carcinoma often follows a neoadjuvant chemoradiation and surgery pathway, with regional practice and individual circumstances considered. Definitive chemoradiation is another curative approach in appropriate cases. For a junctional adenocarcinoma, perioperative durvalumab plus FLOT has a US indication for resectable gastric/GEJ adenocarcinoma; that label should not be expanded to every esophageal primary.

In the United States, adjuvant nivolumab is indicated for adults with completely resected esophageal or GEJ cancer who have residual pathological disease after neoadjuvant chemoradiation. The residual-disease and prior-chemoradiation requirements matter. This is not automatically the same indication after FLOT alone, after a pathological complete response or after radiation without surgery.

Definitive chemoradiation can be used when surgery is unsuitable or not part of the chosen curative plan. Follow-up must look for persistent or recurrent local disease. A scan or superficial biopsy alone cannot guarantee complete eradication. Any surveillance-based approach instead of planned surgery requires an experienced team, a structured reassessment protocol and discussion of salvage options.

Current US first-line options include pembrolizumab with platinum/fluoropyrimidine chemotherapy for eligible unresectable locally advanced or metastatic esophageal cancer with PD-L1 CPS at least 1. For squamous carcinoma, nivolumab with platinum/fluoropyrimidine chemotherapy or with ipilimumab, and tislelizumab with platinum-containing chemotherapy, have PD-L1-positive requirements in their current US indications.

CPS, tumor-cell/TPS and TAP are different scoring approaches. Keep the assay and score on the report rather than translating every result into a single generic percentage. After previous treatment, prior checkpoint exposure matters: the US tislelizumab monotherapy indication after chemotherapy excludes prior PD-(L)1-containing chemotherapy; pembrolizumab monotherapy for previously treated squamous disease requires CPS at least 10.

Advanced adenocarcinoma assessment commonly includes HER2, PD-L1 and MMR/MSI. In the United States, zanidatamab plus tislelizumab and fluoropyrimidine/platinum chemotherapy is approved first-line for adults with HER2-positive unresectable locally advanced or metastatic gastric, GEJ or esophageal adenocarcinoma, defined as IHC 3+ or IHC 2+/ISH+. Zanidatamab plus that chemotherapy without tislelizumab has a narrower HER2 IHC 3+ indication.

The treatment site and testing definition must match the regimen. A gastric/GEJ-only approval, including certain CLDN18.2 treatments, does not automatically cover an esophageal primary. MSI-H/dMMR can identify a separate immunotherapy route under the relevant previous-treatment and local authorization conditions.

Assess weight change and food intake early, before treatment becomes difficult to tolerate. Dietitian support, texture changes, supplements or a feeding route may be needed. A stent can relieve obstruction in selected patients, but its use must fit the planned surgery/radiation and fistula risk; it is not the automatic answer to every swallowing problem.

Coughing with swallowing, recurrent chest infections, inability to drink, major bleeding or sudden severe chest pain require prompt clinical assessment. After esophagectomy, smaller meals and help with reflux, altered digestion and weight maintenance may be needed. Recurrent swallowing difficulty can reflect narrowing or recurrent cancer and needs evaluation.

For another opinion, bring endoscopy and pathology, exact tumor location, staging scans, PD-L1/HER2/MMR reports, previous radiation fields and drug history, plus recent weight and intake records. Ask whether the goal is cure or disease control, how swallowing will be supported and which result would change the next step.