Stages of Esophageal Cancer

Learn about the stages of esophageal cancer and how Texas Oncology provides diagnosis, treatment, and support at every stage across its statewide network.

Stage 0 Stage I Stage II Stage III Stage IV

Stage 0 Esophageal Cancer

Overview

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.

A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of stage 0 esophageal cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

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%.

Strategies to improve treatment

Since this is such an unusual presentation for cancer of the esophagus in the United States, there are essentially no new strategies directed specifically at treatment; however photodynamic therapy may be an option.

Photodynamic treatment: Photodynamic ablation has been used for the palliation of patients with esophageal cancer. Photodynamic treatment involves injection of a light sensitizer into a vein, which is then taken up by cells. A laser is then directed at the cancer cells. The reaction between the laser and the light sensitizer destroys the cells. The objective response rate at one month with this approach has been reported to be 32% for patients receiving photodynamic laser treatment, which compared favorably to the 20% reported for patients receiving thermal-laser treatment.

Stage I Esophageal Cancer

Overview

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.

The following is a general overview of the treatment of stage I esophageal cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

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.

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. Future progress in the treatment of esophageal cancer will result from continued participation in appropriate studies. Currently, there are several areas of active exploration aimed at improving the treatment of esophageal cancer.

Supportive Care: Supportive care refers to treatments designed to prevent and control the side effects of cancer and its treatment. Side effects not only cause patients discomfort, but also may prevent the optimal delivery of therapy at its planned dose and schedule. In order to achieve optimal outcomes from treatment and improve quality of life, it is imperative that side effects resulting from cancer and its treatment are appropriately managed.

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.

Stage II Esophageal Cancer

Overview

Patients with stage II esophageal cancer have cancer that invades into or through the muscular wall of the esophagus, but not into nearby local structures (IIA). When there is regional lymph node involvement with any extent of primary cancer but no invasion of local structures, this is called stage IIB. Stage II cancer may also be referred to as locally advanced.

The following is a general overview of the treatment of stage II esophageal cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Optimal treatment of patients with stage II 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 surgeons, medical oncologists, radiation oncologists, medical gastroenterologists and nutritionists.

Patients with stage II esophageal cancer can be treated with curative intent using either a primary surgical or a primary combined chemotherapy and radiation therapy approach. However, combined chemotherapy and radiation therapy is usually reserved for patients who are not able or do not wish to undergo major surgery. There have been no clinical studies directly comparing combined chemotherapy and radiation therapy with surgery alone for the treatment of patients with stage II esophageal cancer. However, the American Society of Radiology has published guidelines for the treatment of stages I-III esophageal cancer and currently recommends surgery alone as the best treatment for patients with stage II esophageal cancer.

Generally, patients with stage IIB cancer involving the lymph nodes have a worse prognosis than patients with stage IIA cancer without lymph node involvement. Survival of patients with stage IIB is also related to the number of lymph nodes involved with cancer.

Primary treatment with surgery alone

It is difficult to get accurate information about outcomes for patients with stage II esophageal cancer, as most published clinical studies have pooled together the results of patients with stage I-III cancer. In one large clinical study of 160 patients, the average survival duration was 11 months following treatment with surgery alone. In another study involving 110 patients with squamous cell cancer and 124 with adenocarcinoma, the average survival was 16 months, the 5-year survival rate was 20% and 6% of patients died from complications of surgery. The results of this trial indicate that in general, patients with stage IIA cancer experience a better than 20% survival and patients with stage IIB cancer experience a slightly worse outcome. In one study from Japan, the average survival of 14 patients with stage II esophageal cancer following surgery alone was 25 months.

Neoadjuvant therapy (treatment before surgery)

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. The major problems with this approach are the higher mortality rates that occur when radiation therapy and/or chemotherapy are administered before surgery and the delay of surgery for some patients who do not respond to therapy. In most but not all studies, chemotherapy alone, radiation therapy alone or both therapies delivered before surgery have not consistently improved survival following surgery in patients with stage II esophageal cancer. Many current clinical trials are directed at improving outcomes of patients with stage II esophageal cancer by administering newer neoadjuvant treatment regimens containing taxane-based chemotherapy and/or radiation therapy.

In one large clinical trial evaluating neoadjuvant treatment, 300 patients with stage I-II squamous esophageal cancer were randomly assigned to receive surgery alone or chemotherapy and radiation therapy before surgery. There were fewer recurrences of cancer in patients treated with radiation therapy and chemotherapy before surgery. However, this benefit was balanced out by an increase in deaths following surgery in patients who had received chemotherapy and radiation therapy. The average survival was 1.5 years for both groups. Survival at 3 years was approximately 35% for both groups. The presence of lymph node involvement (stage IIB) was associated with a poor outcome, as was the inability to surgically remove all cancer.

In another clinical trial, paclitaxel, Paraplatin^® and fluorouracil chemotherapy were given with radiation therapy to 73 patients with localized (stage I-III) esophageal cancer. Eighty-one percent of all patients underwent surgery and 95% of these had complete resection of all visible cancer. Fifty-four percent of patients undergoing surgery had a complete pathological response, 18% had cancer visible only under the microscope and 32% had residual cancer. A complete pathological response means that no cancer cells were present in the resected cancer specimen. A complete clinical response was observed in 7 of the 14 patients not undergoing surgery. Survival at one year for all patients was 69%, with 50% of patients alive at two years. There were no treatment-related deaths during the chemotherapy and radiation therapy, but 10% of patients died from surgical complications. These results showed that paclitaxel, Paraplatin^® and fluorouracil was a very active drug combination producing a complete clinical and pathologic response in half the patients. However, the 10% death rate following surgery is high and it is unclear what role surgery contributed to overall survival.

With the development of new chemotherapy regimens there will continue to be new clinical trials of neoadjuvant therapy performed in patients with stage II cancer of the esophagus undergoing esophagectomy. The goal of these trials is to develop an effective regimen of chemotherapy and radiation therapy that does not increase the death rate following surgery, but increases survival.

Neoadjuvant and adjuvant treatment

Researchers have also evaluated the combination of neoadjuvant low-dose chemotherapy prior to surgery followed by additional adjuvant chemotherapy after surgery. In the largest clinical trial published, 440 patients with stage II-IV esophageal cancer received treatment with surgery alone or with low-dose neoadjuvant chemotherapy followed by surgery and additional chemotherapy. One year following treatment, the survival rate was 59% for those who received chemotherapy and 60% for those who had surgery alone; at 2 years, survival was 35% and 37%, respectively. In this clinical trial, pre-operative chemotherapy with a combination of Platinol^® and fluorouracil did not improve overall survival among patients with squamous or adenocarcinoma of the esophagus compared to treatment with surgery alone.

Radiation therapy and chemotherapy as primary treatment

Patients with stage II esophageal cancer who cannot or who do not want to undergo surgery may be treated with combined chemotherapy and radiation therapy. Chemotherapy consists of anti-cancer drugs that have 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 esophageal cancer patients have suggested that this strategy may improve remission rates and prolong survival. However, there have been no clinical studies directly comparing combined chemotherapy and radiation therapy with surgery alone for the treatment of patients with stage II esophageal cancer.

In one clinical trial, stage II esophageal cancer patients who received combined chemotherapy and radiation therapy experienced a 5-year survival rate of 20% with local cancer recurrences occurring in 45% of patients. In another clinical trial, 129 patients with stage II and III esophageal cancer were randomly assigned to receive radiation therapy alone or radiation therapy and chemotherapy. The majority of patients had squamous cell cancer and approximately 70% had stage II cancer of the esophagus. Chemotherapy consisted of the combination Platinol^® and fluorouracil. The combined chemotherapy and radiation therapy treatment was associated with a 5-year survival of 27%, compared to 0% for patients receiving radiation therapy alone. The number of local recurrences and distant relapses were fewer in patients receiving combined therapy than in patients receiving radiation therapy alone. The results of this trial indicate that the survival of stage II patients receiving combined therapy is slightly better than 20% and that survival of patients with stage III cancer receiving combined therapy would be worse.

Strategies to improve treatment

New Combination Regimens: Several newer chemotherapeutic drugs have demonstrated an ability to kill esophageal cancer cells in patients with advanced cancer. Research is ongoing to develop and explore single or multi-agent chemotherapy regimens including the taxanes, Gemzar^® and other newer chemotherapy drugs with or without radiation in patients with stage II cancer.

New Adjuvant Regimens: 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. Treatment of patients with radiation therapy, chemotherapy or both therapies after surgery has not been shown to affect survival of patients with stage II cancer of the esophagus. Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies alone or in combination with radiation therapy for use as treatment is an active area of clinical research carried out in phase II clinical trials.

New Neoadjuvant Regimens (Treatment before surgery): Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies is an active area of clinical research carried out in phase II clinical trials. Neoadjuvant therapy may consist of chemotherapy alone or in combination with radiation therapy or biological agents. The potential effectiveness of neoadjuvant chemotherapy and radiation therapy is still being studied in clinical trials, which are primarily evaluating newer combination chemotherapy regimens.

Neoadjuvant and Adjuvant Treatment: Although initial clinical trials have not shown this approach to be superior to surgery alone, researchers continue to evaluate neoadjuvant low-dose chemotherapy prior to surgery followed by additional adjuvant chemotherapy after surgery. In a more recent clinical trial, 42 patients with stage II-IV esophageal cancer received treatment with low-dose neoadjuvant chemotherapy combined with radiation therapy. Thirty-nine of the 42 patients underwent esophagectomy and only one patient died of surgery related problems. After surgery, additional paclitaxel based chemotherapy was given. Overall, 51% of patients were alive 2 years after treatment and 91% of the patients achieving a complete response to treatment survived. This clinical trial suggests that decreasing the dose of neoadjuvant chemotherapy may reduce mortality associated with surgery and the addition of paclitaxel adjuvant therapy could potentially improve outcomes.

Stage III Esophageal Cancer

Overview

Patients with stage III esophageal cancer have cancer that invades through the wall of the esophagus and has spread to the lymph nodes and/or invaded adjacent structures. This is a very common stage for presentation of esophageal cancer. Stage III cancer may also be referred to as locally advanced.

The following is a general overview of the treatment of stage III esophageal cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Optimal treatment of patients with stage III 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.

For patients with stage III esophageal cancer, there are essentially two currently available treatment choices: chemotherapy and radiation therapy before surgery or chemotherapy and radiation therapy without surgery. Surgery alone is not usually advised for patients with stage III esophageal cancer except as necessary for palliation for difficulty in swallowing. There may be some exceptions to this recommendation for patients with stage III cancer who only have minimal lymph node nodal involvement with cancer or those with minimal spread of cancer to adjacent structures.

The American Society of Radiology has published guidelines for the treatment of esophageal cancer and has recommended chemotherapy and radiation therapy and no surgery for patients with stage III esophageal cancer. However, many current clinical trials are directed at improving outcomes of patients with stage III esophageal cancer by administering chemotherapy and radiation therapy before surgery (neoadjuvant treatment). This approach assumes that chemotherapy and radiation therapy will increase the likelihood of curative surgery being performed in patients who are inoperable at diagnosis. It also presumes that surgery can eliminate residual cancer that remains after treatment with chemotherapy and radiation therapy. The major problem with this approach is the high mortality rate following surgery, which is often increased by currently utilized radiation therapy and chemotherapy programs.

Patients with stage III esophageal cancer with extensive local and lymph node spread are also often included in clinical trials along with patients with metastatic stage IV esophageal cancer to evaluate new chemotherapy regimens.

Chemotherapy and radiation therapy as primary treatment

Chemotherapy is usually combined with radiation therapy for the treatment of patients with stage III esophageal cancer. Chemotherapy refers to anti-cancer drugs designed to treat cancer systemically. Chemotherapy and radiation therapy may act together to increase the destruction of cancer cells. Chemotherapy may also destroy cancer cells in locations not reached by radiation therapy.

The results of several clinical studies performed in esophageal cancer patients receiving concurrent chemotherapy and radiation therapy have indicated that this strategy may improve remission rates and prolong survival compared to surgery with or without radiation. In general, concurrent radiation and chemotherapy results in 3-5 year survival rates of 20-30%, with average survival rates of less than one year. The combination of radiation and chemotherapy is superior to treatment with radiation therapy alone.

For example, a randomized clinical trial involving 129 patients with stage II and III esophageal cancer compared radiation therapy alone to radiation therapy and chemotherapy. The majority of patients had squamous cell cancer. Approximately 70% of patients participating in this clinical trial had stage II and 30% had stage III esophageal cancer. Chemotherapy consisted of a combination of Platinol^® and fluorouracil. The combined chemotherapy and radiation therapy treatment was associated with a 5-year survival of 27%, compared to 0% for patients receiving radiation therapy alone. The number of local recurrences and distant relapses were fewer in patients receiving combined therapy than in patients receiving radiation therapy alone.

Neoadjuvant therapy

Neoadjuvant therapy has the potential advantages of delivering immediate therapy to destroy any cancer cells that may have already spread away from the esophagus and reducing the size of the cancer, thereby allowing easier surgical resection. The role of neoadjuvant chemotherapy and radiation therapy before surgery in patients with localized esophageal cancer is controversial. In some clinical studies, patients receiving neoadjuvant chemotherapy and radiation therapy have experienced improved outcomes compared to surgery alone. Unfortunately, a higher death rate following surgery has also been reported, which may cancel out any benefit from control of cancer by this more intensive treatment approach. Clinical trials of new more effective and potentially less toxic chemotherapy regimens continue to be tested because current results of treatment with or without surgery remain unsatisfactory.

Doctors have performed a small clinical study that compared surgery alone to neoadjuvant chemotherapy followed by surgery. In this study, 74 patients with squamous cell esophageal cancer were treated with Platinol^® and fluorouracil before surgery and compared to 73 patients who were treated with surgery alone. The average survival of patients treated with neoadjuvant chemotherapy before surgery was 17 months, compared to 13 months for patients treated with surgery alone. Patients who responded to chemotherapy survived an average of 42 months, which was better than the 14 months observed in the group treated with surgery alone. This small study suggested that some patients might have benefited from neoadjuvant chemotherapy administered before surgery.

In another small clinical study, 58 patients with localized esophageal cancer were randomly assigned to receive chemotherapy, radiation therapy and surgery and 55 patients were randomly assigned to receive surgery alone. The majority of these patients had stage III cancer. The results indicated that 25% of patients achieved a complete pathological response after chemotherapy and radiation therapy. The average survival was 16 months for patients receiving combined treatment and 11 months for those receiving surgery alone. The 3-year survival rate was 32% for patients receiving combined therapy and 6% for patients receiving surgery alone. This clinical trial, in addition to the previous one, suggests that combined modality treatment appears superior to treatment with surgery alone for stage III esophageal cancer.

A more recent clinical trial evaluated newer chemotherapy drugs. In this trial, 73 patients with localized (stage I-III) esophageal cancer received paclitaxel, Paraplatin^® and fluorouracil chemotherapy with radiation therapy before surgery. Following chemotherapy and radiation, 81% of patients underwent surgery and 95% of these had complete resection of all visible cancer. The results indicated that 54% of patients undergoing surgery had a complete pathological response, 18% had cancer visible only under the microscope and 32% had residual cancer. Of the 14 patients who did not undergo surgery, 7 experienced a complete response. Survival at one year for all patients was 69% and at two years was 50%. The average survival was 24 months. There were no treatment related deaths during the chemotherapy and radiation therapy, but 10% of patients died from surgical complications. These results are impressive because of the 50% complete response rate, which is the best reported. However, the 10% death rate following surgery is high and it is unclear what role surgery contributed to overall survival.

Neoadjuvant and adjuvant treatment

Researchers have also evaluated neoadjuvant low-dose chemotherapy prior to surgery followed by additional adjuvant chemotherapy after surgery. In the largest clinical trial published, 440 patients with stage II-IV esophageal cancer received treatment with surgery alone or with low-dose neoadjuvant chemotherapy followed by surgery and additional chemotherapy. One year following treatment, the survival rate was 59% for those who received chemotherapy and 60% for those who had surgery alone; at 2 years, survival was 35% and 37%, respectively. In this clinical trial, preoperative chemotherapy with a combination of Platinol^® and fluorouracil did not improve overall survival among patients with squamous or adenocarcinoma of the esophagus compared to treatment with surgery alone.

Strategies to improve treatment

New Adjuvant Regimens (treatment after surgery): Treatment of patients with radiation therapy, chemotherapy or both combined after surgery has not been shown to affect survival of patients with stage III esophageal cancer. Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies alone or in combination with radiation therapy for use as treatment is an active area of clinical research carried out in phase II clinical trials. Currently, the taxanes, Gemzar^® and other newer chemotherapy drugs are being evaluated in patients with stage III cancer since these are among the most active agents developed for the treatment of esophageal cancer.

Neoadjuvant and Adjuvant Treatment: Although initial clinical trials have not shown this approach to be superior to surgery alone, researchers continue to evaluate neoadjuvant chemotherapy prior to surgery followed by additional adjuvant chemotherapy after surgery. In a more recent clinical trial, 42 patients with stage II-IV esophageal cancer received treatment with low-dose neoadjuvant chemotherapy combined with radiation therapy. Following neoadjuvant treatment, 39 of the 42 patients underwent esophagectomy and only one patient died of surgery related problems. After surgery, patients received additional paclitaxel-based chemotherapy. Overall, 51% of patients were alive 2 years after treatment and 91% of the patients achieving a complete response to treatment survived. This clinical trial suggests that decreasing the dose of neoadjuvant chemotherapy may reduce mortality associated with surgery and the addition of paclitaxel adjuvant therapy could potentially improve outcomes.

Stage IV Esophageal Cancer

Overview

Patients with stage IV esophageal cancer have metastatic cancer that has spread to distant sites.

The following is a general overview of the treatment of stage IV esophageal cancer. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied to your situation. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Optimal treatment of patients with stage IV 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, gastroenterologists and nutritionists.

There are currently no standard curative therapies for treatment of stage IV esophageal cancer. The predominant symptom of esophageal cancer is dysphagia, which simply means difficulty in swallowing food and liquids. There are specific treatments that can be administered that can result in short-term benefit and improvement in nutrition. Current treatment approaches are primarily directed at controlling the symptoms of cancer and prolonging survival. A number of treatment options are currently utilized alone or in combination to achieve optimal results.

Surgery for palliation

Patients with stage IV esophageal cancer often have widespread cancer at the time of diagnosis and cannot be cured with surgery. There is controversy over how best to treat patients who cannot undergo surgery with curative intent. In one clinical study, doctors compared the outcomes of 39 patients with stage IV esophageal cancer who underwent an esophagectomy for palliation with the outcomes of 49 patients with stage IV esophageal cancer who underwent more complete removal of cancer. Both groups of patients experienced significant improvement with regard to both the quantity and quality of food intake and a reduction in the severity of eating related symptoms. After 9 months, patients in the palliative group experienced more pain and a poorer quality of life, but there were no differences in sleep, leisure activity and performance scores when compared to the other group. This study suggests that palliative esophagectomy relieves symptoms in the majority of patients with inoperable esophageal cancer. It could also be argued that both groups had palliative surgery since the majority of patients who undergo surgery with curative intent have rapid recurrence of cancer in the first year or two after surgery.

Chemotherapy

Single chemotherapy drugs such as Platinol^®, fluorouracil, Mutamycin^®, doxorubicin, and Ellence^® can result in clinical remissions in patients with esophageal cancer. Historically, standard chemotherapy treatment regimens often utilized Platinol^®, flourouracil and Ellence^® or Mutamycin^®. The overall response rate for these combination regimens is approximately 40% and the average survival duration is 8-10 months. Recent studies indicate that taxanes (paclitaxel and Taxotere^®) may be the most active single chemotherapy drugs for the treatment of esophageal cancer, with complete remissions occurring in up to 15% of patients. Other agents that have been or are being evaluated include Camptosar^® and Gemzar^®. All current clinical trials involve various combinations of drugs.

For example, in a recently published clinical trial, 61 patients with advanced unresectable or metastatic esophageal cancer were treated with Platinol^®, fluorouracil and paclitaxel. Thirty patients had adenocarcinoma and 31 had squamous cell cancer. The overall response rate was 48% for all patients; however, the complete response rate was 20% for patients with squamous cancer and only 3% for patients with adenocarcinoma. The average duration of response was 5.7 months and the average survival was 10.8 months. There were no treatment related deaths. This regimen resulted in a complete response rate of 20% in patients with squamous cell cancer, which is higher than other reported regimens.

Camptosar^® is another new chemotherapy drug with activity against cancers of the gastrointestinal tract. In one study, 35 patients with metastatic or unresectable adenocarcinoma or squamous cell esophageal cancer were treated with a combination of Camptosar^® and Platinol^®. Major clinical responses were observed in 20 patients (57%) and 2 patients experienced complete disappearance of their cancer. Responses were observed both in patients with adenocarcinoma and those with squamous cell carcinoma. The average duration of response was 4 months. In 20 patients with difficulty swallowing, 90% had improvement or resolution of their symptoms. Responding patients also experienced an improvement in their quality of life, primarily because of reductions in pain and improvement in their emotional state. The therapy was well tolerated and side effects were relatively mild.

Currently available combination chemotherapy treatment for stage IV cancer results in complete remission in up to 20% of patients, with average survival of 8-12 months. As newer drugs, such as the taxanes, Camptosar^®, and Gemzar^®, are incorporated into regimens, this may continue to improve.

Other treatment modalities

Many other treatment modalities are utilized to prolong survival and quality of life for patients with esophageal cancer.

Thermal Laser: Thermal laser coagulation performed by endoscopy can provide temporary relief of dysphagia. Laser ablation appears to be most helpful for treating polypoid cancers that grow into the esophagus causing occlusion. Laser treatment is less effective for upper esophageal cancers or cancers of the gastroesophageal junction. A multi-center clinical trial has compared photodynamic laser therapy to thermal laser ablation for the palliation of patients with esophageal cancer who experience difficulty swallowing food. In general, photodynamic laser therapy was more effective than thermal laser treatment.

Photodynamic Treatment: Photodynamic ablation has been used for the palliation of patients with esophageal cancer. Photodynamic treatment involves injection of a light sensitizer into a vein, which is then taken up by cells. A laser is then directed at the cancer cells. The reaction between the laser and the light sensitizer destroys the cells. The objective response rate at one month with this approach has been reported to be 32% for patients receiving photodynamic laser treatment, which compared favorably to the 20% reported for patients receiving thermal-laser treatment.

Esophageal Dilatation: Frequently, after the administration of chemotherapy, radiation therapy, laser or photodynamic treatment, the area of the esophagus with cancer can be constricted or narrowed. Narrowing of the esophagus may be due to recurrent cancer or to treatment induced strictures or both. Relief of this constriction by dilation can temporarily improve swallowing. During esophageal dilation, a physician uses endoscopic or fluoroscopic guidance to pass flexible dilators (mercury filled rubber tubes) through the mouth. Increasing diameters of dilators, called bougies, are gradually introduced until the difficulty in swallowing resolves. One clinical study reported a 92% success rate for dilation. The duration of symptom relief after successful dilatation varies from days to weeks. One complication of esophageal dilation is the potential for perforation; however, this occurs only rarely. In a large study of 154 patients, a total of 3,140 dilators were passed before, during and after radiation therapy and resulted in only two perforations.

Esophageal Stents or Prostheses: Stents are rigid tubes that stay in the esophagus to keep it open. Recently, a clinical study evaluated the use of esophageal stents over a 4-year period for the management of patients with inoperable esophageal cancer. In a group of 160 patients with esophageal cancer,159 had stents placed successfully. In this study, a traditional rigid tube was placed in 84 patients and metallic self-expanding stents were placed in 75 patients. After placement of the stents, chemotherapy and/or radiation therapy was administered to 82 patients. The results indicated that 11% of patients had complications, including displacement of the stent, incomplete expansion of the stent, perforation of the esophagus or bleeding. Swallowing was improved in 97% of patients. These doctors concluded that placement of stents to improve swallowing was a relatively safe palliative procedure. Self-expanding metallic stents were thought to be preferable to rigid stents for maintaining an open esophagus.

Strategies to improve treatment

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

New Chemotherapy Regimens: Development of new multi-drug chemotherapy treatment regimens that incorporate new or additional anti-cancer therapies is an active area of clinical research carried out in phase II clinical trials. These studies are performed in patients with stage IV or recurrent esophageal cancer.

Phase I Trials: New chemotherapy drugs or other anti-cancer therapies continue to be developed and evaluated in phase I clinical trials. The purpose of phase I trials is to evaluate new therapies in order to determine the best way of administering the drug and to determine whether the drug has any anti-cancer activity in patients with esophageal cancer. Patients with stage IV esophageal cancer should consider participation in phase I trials.

Multiple Drug Resistance Inhibitors: Esophageal cancer can be drug resistant at the outset of treatment or develop drug resistance after treatment. Several drugs are being tested to determine if they will overcome or prevent the development of multiple drug resistance in esophageal and other cancers.

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 dysfunction 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 death or efforts to make the immune system kill cancer cells. A few gene therapy studies are being carried out in patients with esophageal cancer.