Medically reviewed by C.H. Weaver M.D. Medical editor 8/2018

Patients with stage 0 esophageal cancer have carcinoma in situ, which is characterized by cancer cells that involve only the superficial (top) layer of cells lining the esophagus. Although these are usually small cancers, they may, on occasion, spread superficially and involve a large part of the esophagus.

Stage 0 esophageal cancer is rare in the United States, but is more common in Asia, where patients at risk of developing esophageal cancer are subjected to routine periodic esophagoscopy. Treatment for stage 0 esophageal cancer involves surgical resection with wide margins. If there is no superficial spread, most stage 0 cancers can be removed through an endoscope. The cure rate is greater than 90%.

Patients with stage I esophageal cancer have cancer that invades beneath the surface lining of the esophagus, but not into the muscle wall of the esophagus, the lymph nodes or other locations in the body. This is also called an early, superficial or localized cancer that is surgically resectable.

Optimal treatment of patients with stage I esophageal cancer often requires more than one therapeutic approach. Thus, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving medical oncologists, radiation oncologists, surgeons, medical gastroenterologists and nutritionists.

Stage I esophageal cancer is relatively uncommon. It is difficult to estimate the outcomes of patients with stage I esophageal cancer who do not undergo surgery as primary therapy because clinical staging is frequently inaccurate. Many patients who have clinical stage I cancer will in fact have more extensive cancer discovered at surgery. For example, in one clinical study from Japan, almost half of patients who were originally diagnosed with stage I esophageal cancer were found to have previously undetected cancer in local lymph nodes and were reclassified as stage IIB cancer following surgery. Patients with stage I esophageal cancer can be treated with curative intent using either surgery or chemotherapy and radiation therapy. Currently, the chemotherapy and radiation therapy approach is usually reserved for patients who cannot tolerate surgery.

Primary Treatment with Surgery Alone: The current preferred treatment for patients with stage I esophageal cancer who are in good clinical condition is esophagectomy (complete removal of the esophagus). In addition, when patients truly have cancer that does not invade the muscle wall of the esophagus, surgery can frequently be performed through an endoscope. In one clinical study from Japan, the 5-year survival rate for patients with stage I esophageal cancer was 86% following endoscopic surgical resection. In another study from Japan, the average survival for 6 patients treated with surgery alone was 15 years.

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Primary Treatment with Radiation and Chemotherapy:

Patients who are not well enough or who do not wish to undergo major surgery can be treated with a combination of radiation therapy and chemotherapy. Chemotherapy is the treatment of cancer with anti-cancer drugs. Chemotherapy has the ability to kill cancer cells. Chemotherapy and radiation therapy may act together to increase the destruction of cancer cells. The results of several clinical studies using concurrent chemotherapy and radiation therapy in patients with esophageal cancer have indicated that combination chemotherapy and radiation may improve remission rates and prolong survival compared to chemotherapy or radiation therapy alone. In one clinical study, 26 patients with stage I esophageal cancer received radiation therapy combined with fluorouracil and Mutamycin® chemotherapy, resulting in a 3-year survival rate of 73%. Since no direct comparisons between surgical resection and radiation plus chemotherapy have been made, it is unknown whether these results are equivalent to esophagectomy.

Strategies to Improve Treatment

The progress that has been made in the treatment of esophageal cancer has resulted from improved patient participation in clinical studies. Currently, there are several areas of active exploration aimed at improving the treatment of esophageal cancer.

New Combination Regimens: Several newer chemotherapeutic drugs have demonstrated an ability to kill, or incapacitate, esophageal cancer cells in patients with advanced cancer. Research is ongoing to develop and explore single or multi-agent chemotherapy regimens in combination with radiation.

Adjuvant Treatment (treatment after surgery): Treatment with radiation therapy, chemotherapy or a combination following surgery has not been shown to affect survival of patients with stage I esophageal cancer. The development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies alone or in combination with radiation therapy is an active area of clinical research carried out in phase II clinical trials. Newly developed regimens are only utilized to treat patients with stage I esophageal cancer when they are proven superior to current chemotherapy regimens in patients with more advanced cancer. Currently, the chemotherapy agents paclitaxel and Taxotere® are being evaluated in patients with stage I cancer since these are among the most active agents for the treatment of squamous cell esophageal cancer.

Neoadjuvant Therapy: Chemotherapy and/or radiation therapy administered prior to surgery is referred to as neoadjuvant therapy. In theory, neoadjuvant therapy can decrease the size of the cancer, making it easier to remove with surgery. There is currently no evidence that radiation therapy and/or chemotherapy administered prior to surgery is of benefit for patients treated with surgery for stage I esophageal cancer. In one clinical study, 297 patients with stage I-II squamous esophageal cancer were treated with surgery alone or with chemotherapy and radiation therapy before surgery and the results were then directly compared. There were fewer recurrences of cancer in patients treated with radiation therapy and chemotherapy. However, this benefit was balanced out by an increase in side effects resulting in more deaths following surgery in the patients who had received chemotherapy and radiation therapy. The potential effectiveness of neoadjuvant chemotherapy and radiation therapy is still being studied in clinical trials, which are primarily evaluating newer combination chemotherapy regimens.

Gene Therapy: Currently, there are no gene therapies approved for the treatment of esophageal cancer. Gene therapy is defined as the transfer of new genetic material into a cell for therapeutic benefit. This can be accomplished by replacing or inactivating a dysfunctional gene or replacing or adding a functional gene into a cell to make it function normally. Gene therapy has been directed towards the control of rapid growth of cancer cells, control of cancer cell death and efforts to facilitate immune mediated death of cancer cells. A few gene therapy studies are being carried out in patients with refractory esophageal cancer. If successful, these therapies could be applied to patients with earlier stages of esophageal cancer.