ON THIS PAGE: You will find information about the number of people who are diagnosed with esophageal cancer each year. You will also read general information on surviving the disease. Remember, survival rates depend on several factors. Use the menu to see other pages.
This year, an estimated 17,650 adults (13,750 men and 3,900 women) in the United States will be diagnosed with esophageal cancer. The disease accounts for 1% of cancers diagnosed in the United States. It is diagnosed more often in other parts of the world.
It is estimated that 16,080 deaths (13,020 men and 3,060 women) from this disease will occur this year. Esophageal cancer is the seventh most common cause of cancer death among men.
The 5-year survival rate tells you what percent of people live at least 5 years after the cancer is found. Percent means how many out of 100. The 5-year survival rate for people with esophageal cancer is 19%.
However, survival rates depend on several factors, including the stage of the cancer when it is first diagnosed. The 5-year survival rate of people with cancer located only in the esophagus is 45%. The 5-year survival rate for those with disease that has spread to surrounding tissues or organs and/or the regional lymph nodes is 24%. If it has spread to distant parts of the body, the survival rate is 5%.
It is important to remember that statistics on the survival rates for people with esophageal cancer are an estimate. The estimate comes from annual data based on the number of people with this cancer in the United States. Also, experts measure the survival statistics every 5 years. So the estimate may not show the results of better diagnosis or treatment available for less than 5 years. Talk with your doctor if you have any questions about this information. Learn more about understanding statistics.
Statistics adapted from the American Cancer Society’s (ACS) publication, Cancer Facts & Figures 2019, and the ACS website (January 2019).
The next section in this guide is Medical Illustrations. It offers drawings of body parts often affected by esophageal cancer. Use the menu to choose a different section to read in this guide.
Thinking Outside the Box With Esophageal Cancer Treatment
“It was the week before Thanksgiving, November 2017, that I had my first incidence of clogging when swallowing,” Smalley says. In his business, he often worked long hours and ate dinner late, so he attributed the clogging to eating too fast and chose not to seek immediate medical help.
But after six months of increasingly painful swallowing, in June 2018, Smalley decided to heed the advice of his gastroenterologist to undergo a colonoscopy and endoscopy, procedures that use instruments to view the inside of the colon and esophagus.
“The gastroenterologist said the colonoscopy was clean as a whistle, but when he showed me pictures from my esophagus, I could tell by the look on his face that some- thing was wrong,” Smalley recalls.
Biopsies of his esophagus taken during the procedure revealed that Smalley, who does not drink or smoke but did suffer from gastrointestinal reflux disease, or GERD, had esophageal cancer.
An Uncommon Cancer
Esophageal cancers can occur in either the upper part of the esophagus, called the upper esophageal sphincter, or the lower part, which connects with the stomach; disease there is called gastroesophageal junction cancer.
Esophageal cancers are divided into two main types. Squamous cell carcinoma, which accounts for about 25% of esophageal cancers, occurs in the cells lining the length of the esophagus and is usually diagnosed in the upper region. The more common esophageal adenocarcinoma starts in the mucus-forming gland cells and usually occurs in the lower third of the organ.
“Historically, squamous cell carcinoma was more common, as it is a histology associated with chronic alcohol abuse and cigarettes,” says Dr. Ronan J. Kelly, director of the Charles A. Sammons Cancer Center at Baylor Scott & White Health in Dallas and an adjunct associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine in Baltimore. “As we have seen a decrease in the incidence of smoking, the rates of esophageal squamous cell carcinoma are decreasing rapidly and reports of adenocarcinoma, associated with lifestyle factors like obesity and chronic gastro- esophageal reflux disease, are increasing dramatically.”
The American Cancer Society estimates that esophageal cancer makes up about 1% of all cancers diagnosed in the United States. It is estimated that, in 2019, there will be about 17,500 new esophageal cancer cases diagnosed and 16,000 esophageal cancer deaths.
Factors that increase a person’s risk of esophageal cancer include heavy tobacco or alcohol use, older age — the median age at diagnosis is 68 — or having a precancerous condition called Barrett’s esophagus. Additionally, more men than women receive a diagnosis of esophageal cancer. Infection with human papillomavirus is also a risk factor.
More than half of cases diagnosed will be caught in either the localized stage, in which disease is confined to the esophagus, or the regional stage, in which disease has spread only to lymph nodes in the same region of the body as the tumor. Four in 10 people receive a diagnosis of meta- static disease, which means it has spread to other organs.
“Esophageal cancer still has one of the worst prognoses compared with other cancers,” Kelly says, adding that patients who have metastatic disease face the poorest health outcomes.
Of course, that means that chances for survival are best if the disease is caught early, according to Dr. Manish A. Shah, chief of the solid tumor service and director of the gastrointestinal oncology program at NewYork- Presbyterian/Weill Cornell Medicine Medical Center.
One of the most commons signs and symptoms of esophageal cancer is painful or difficult swallowing, according to Shah. Other commons signs include weight loss, pain behind the breastbone, hoarseness and cough, indigestion or a lump under the skin. “However, there are a number of patients who do not have any of these issues, yet can still develop esophageal adenocarcinoma,” Kelly says.
An Atypical Case
Dana Deighton was just 43 when she received a diagnosis of esophageal cancer in 2012. A marketing professional and mother of three, she was part of a very active family that enjoyed sports and outdoor activities.
Deighton’s attention turned to her health in 2012 when she began to experience a variety of odd symptoms that were attributed to a suspected but unconfirmed case of the autoimmune disease lupus. After successfully treating those symptoms for about six months, Deighton noticed a new set of issues. “It began as stomach pain that was nonspecific, and I thought maybe it was irritable bowel syndrome,” Deighton recalls. “Then the stomach pain began to migrate to my back, and I wasn’t able to even sit at a table comfortably for a long time.”
As the pain grew worse, Deighton explored possible food intolerances, such as a gluten allergy, but had no success in relieving her symptoms. “During yet another trip to my general practitioner, I happened to throw my hands up in a type of frustration and felt a big lump on my neck, about the size of a large grape,” she says. “That is when I knew something was not right.”
Deighton underwent an ultrasound and biopsy of the lymph node, but tests came back nondefinitive. Continued diagnostic tests looking for ovarian cancer, then lung cancer, then colorectal cancer eventually revealed a tumor in her lower esophagus that had already begun to spread.
“All the leading doctors up and down the East Coast said, ‘You don’t have much time. We would recommend palliative care so you can enjoy your time with your family,’” Deighton says. “I knew they were basing this prognosis on all the other cases they treat — men who are over 65 and had smoked or drank, or had an unhealthy lifestyle.”
Because she did not fit the mold of a typical patient with esophageal cancer, Deighton was determined to find treatment that was right for her.
Standard of Cancer
Surgery — called esophagectomy — is traditionally among the most common treatments for patients who have localized or regional esophageal cancer. Surgery alone is typically used only in patients with early-stage disease, according to Shah. During an esophagectomy, the surgeon removes the diseased part of the esophagus and connects the remaining healthy parts to the stomach.
For patients with locally advanced disease or those who may not qualify for surgery, treatment will start with a combination of chemotherapy and radiation therapy. New study findings show that coupling chemotherapy with prehabilitation — nutritional and psychosocial support and exercise — can shorten patients’ hospital stays and frequency and boost their nutritional status.
“Standard treatment for the last several years has been combination chemotherapy with a platinum agent like Taxol (paclitaxel) combined with carboplatin plus radiation,” Shah says. Prior to his surgery, Smalley received this regimen, a strategy called neoadjuvant chemotherapy, which is given in an attempt to shrink the tumor before it is surgically removed.
Other chemotherapy combinations can be used depending on the patient’s age, health and history of previous drug regimens, as well as the location of the tumor. Eventually, doctors may be able to test patients to assess whether chemoradiotherapy is likely to eliminate most or all of the cancer so that surgery can be avoided. Possible methods are being investigated in clinical trials, such as one in China involving locally advanced disease; researchers will look for resistance biomarkers in tissue and blood samples and through positron emission tomography, or PET scans. Another predictive measure recently tested found that patients whose tumors have poorly differentiated cells, which tend to be faster-growing and more aggressive, are most likely to experience cancer recurrences after chemoradiation and surgery appeared to eradicate their cancer. This could help doctors tailor treatment and surveil- lance to individuals.
Smalley was given chemotherapy treatments combined with external-beam radiation, which comes from a machine outside the body and focuses on the cancer. Certain patients with more advanced esophageal cancer may undergo internal radiation therapy, or brachytherapy, which involves placing radioactive material inside the esophagus for a period of time. This procedure is mainly for symptom relief.
In Deighton’s case, all her physicians agreed on one thing: Starting systemic chemotherapy was critical. Although standard of care for metastatic cases is usually a chemo- therapy regimen known as FOLFOX (leucovorin, fluorouracil and oxaliplatin), an insurance hiccup denied coverage of the pump required for the delivery of one of those medications. Knowing she was not going home without some sort of treatment, her doctor switched to EOX (epirubicin, oxaliplatin and capecitabine). That regimen is no longer typically used to treat esophageal cancer, but it didn’t require a pump, according to Dr. David H. Ilson, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City.
“This was a blessing for me, because the regimen was really effective and resulted in residual resolution in some of my distant metastases,” Deighton says.
Patients like Deighton are often given chemotherapy alone for their metastatic disease. Radiation therapy may be added to relieve symptoms associated with the disease, such as pain or difficulty swallowing. Deighton did not have these problems, but after completing her chemotherapy, she was determined to pursue radiation therapy with curative intent. She found a few written cases in which radiologists suggested that this could further resolve the cancer, and she discussed the idea with several physicians. Just one was willing to try it.
“My physician recognized my health, instead of just my cancer, and that I may be able to handle some outside-of-the- box treatment ideas,” Deighton says. “The trust he cultivated was very powerful, yet never reckless or without a strong dose of what could be a disappointing and uncomfortable reality.”
Her outside-the-box radiation resulted in further resolution and was followed by a high-risk esophagectomy, an unusual treatment for a patient with stage 4 disease.
“It was dangerous, and every day I know how lucky I am,” Deighton says.
In recent years, several targeted treatments have also been approved for esophageal cancer. “Targeted treatments are reserved for stage 4 metastatic disease,” Ilson explains.
Patients with advanced disease should be tested for the status of their HER2 protein, which drives cancer; 10% to 30% of gastroesophageal adenocarcinomas express too much of this protein. The drug Herceptin (trastuzumab) an antibody against HER2, targets and disables the protein and is approved for gastroesophageal junction cancers. The disease can also be treated with any of five biosimilars that are nearly identical to Herceptin, including Kanjinti (trastuzumab-anns), which was approved in June.
After completing her surgery, Deighton’s physicians wanted to continue to fight her disease by treating her with Herceptin. Similar to many chemotherapies, Herceptin is given by infusion once every three weeks, usually in combination with chemotherapy.
If treatment with Herceptin is not successful or patients do not have HER2-positive disease, the next targeted agent to consider is Cyramza (ramucirumab), which targets the VEGF protein, according to Ilson. This protein tells the body to make new blood vessels, which can feed tumors and help them grow. “There are some data that ramucirumab can be given alone, but that is less effective than when it is combined with a chemotherapy like paclitaxel,” Ilson says.
Additional cellular signaling pathways that may help drive this cancer type — PARP, EGFR, PIK3CA and FGFR — are being studied and could lead to new targeted drugs for esophageal cancer. Signaling pathways orchestrate the activities of cells, and glitches in communication along them can give rise to cancer or other diseases.
A third precision approach involves a type of immunotherapy called immune checkpoint inhibition. Immunotherapy attempts to use a person’s own immune system to fight their cancer. The only Food and Drug Administration (FDA)-approved immunotherapy for gastroesophageal junction cancers is Keytruda (pembrolizumab), which targets the protein PD-1. “It is approved for gastroesophageal junction or gastric cancers, but the National Comprehensive Cancer Network guidelines typically apply the same criteria for those cancers to esophageal cancers,” Ilson explains.
Keytruda can be used in patients whose disease has progressed or recurred on multiple prior lines of chemo- therapy or whose cancer is positive for the protein PD-1 or for PD-L1, a molecule that binds to it. Overexpression of PD-L1 is estimated to occur in 40% of esophageal squamous cell carcinomas and 18% of adenocarcinomas. In addition, Keytruda can be used to treat cancer that is microsatellite instability (MSI)-high, meaning it has trouble repairing its own DNA when damaged. However, Ilson says, less than 1% of patients with esophageal cancer have MSI-high disease, as Deighton does.
Prior to Keytruda’s FDA approval in 2017 and after treatment with Herceptin, Deighton’s disease began to spread again. Her oncologists began off-label treatment with another PD-1-targeting immunotherapy, Opdivo (nivolumab). “I have been on it about three years now, and my doctors tell me I am one of the furthest out with gastroesophageal junction cancer who continues to do well,” Deighton says.
Opdivo is not approved for esophageal cancer, but recently released data from a phase 3 clinical trial showed that, compared with chemotherapy, it extended the lives of patients with advanced or recurrent esophageal cancer, regardless of PD-L1 status.
Smalley also underwent treatment with Opdivo in combination with his neoadjuvant chemotherapy and radiation as part of a clinical trial at Johns Hopkins.
“Immune checkpoint inhibitors are being looked at in earlier lines of treatment for metastatic disease and in combination with preoperative treatment, but only in the context of clinical trials,” Ilson says.
Before his esophagectomy, Smalley’s surgeon warned him that during recovery, he would feel like he had been hit by National Football League defenseman Ray Lewis. “What he didn’t tell me was how many times Ray Lewis was going to hit me,” Smalley jokes.
After surgery, he spent two days in the intensive care unit and about 10 days in the hospital.
Recently, Smalley’s first follow-up showed that he is clear of disease, and his esophagus has healed enough so his feeding tube can be removed. Although he is still adjusting, he is hopeful that he will get back to work soon.
Deighton, who is more than five years out from her stage 4 diagnosis with no evidence of disease, has beaten the odds and had more time to adjust to life after cancer. Her experience led her to a career as a project manager for the company Inspire, a social network for health, which aims to accelerate medical progress through a world of connected patients.
Both Smalley and Deighton credit their successful outcomes to many of the more recent advances in esopha- geal cancer treatment and to their own willingness and drive to find physicians that fit their needs.
As part of her knowledge gathering, Deighton researched patient advocacy groups like the Esophageal Cancer Action Network, of which she is now a board member. “You have to advocate for yourself,” she says. “You have to have a relationship with your doctor, read and gain knowledge, have (an) in-depth conversation and ask questions.”
The future remains uncertain but hopeful for Smalley and Deighton, and both are eager to generate greater awareness about esophageal cancer.
“Who knew that something like heartburn could cause cancer? I certainly didn’t,” Smalley says. “I’m hopeful that my treatment will help me, but when I was diagnosed, I knew I wanted to do more to help others, like participate in the clinical trial and raise awareness to help other people learn about esophageal cancer.”
When I walked through the doors of the hospital, I knew was in the right place. At CTCA, I didn’t see one doctor; I saw a team of doctors and clinicians who consulted with one another about treatment that would be appropriate for me. I was treated with compassionate care as a whole individual. I appreciated that. Together, we created a treatment plan that was tailored to me and my needs.
After completing diagnostic testing at CTCA, I found out my cancer was stage III. In April 2016, I started six weeks of chemotherapy and radiation to fight the cancer. I continued to work part-time every day from 6 to 11 a.m. I would then go to CTCA to complete my treatments. I took advantage of several supportive therapies, such as nutrition and naturopathic support, to combat my side effects, including nausea and fatigue.
In August 2016, I underwent surgery to remove my stomach and part of my esophagus, and to then reattach the small intestines to my remaining esophagus. I was off the feeding tube two days after surgery. I was determined to get up and get moving during my recovery, which I felt went well. While my wife was at work, I would walk around our neighborhood.
Throughout my treatment, I had lost a lot of weight, and there were times I wasn’t sure if I could make it through. But I trusted in God and my care team to help me finish it. My wife also encouraged me and stood by my side. With their support, I completed my treatment plan.
My path ahead
Today, I have no evidence of disease, and I return to CTCA every three months for checkups. After my surgery, I did take oral chemotherapy for three months to reduce my risk of recurrence. While I now eat smaller and more frequent meals since I no longer have a stomach, I am adjusting to my new normal. I have good days and bad, but I always have a positive attitude knowing that I survived.
I am continuing my faith studies, and we will see where that path eventually takes me. I am an active volunteer at my church and in my community, and I participate in 5K races to raise funds for cancer awareness and research. I frequently share with others what I have learned about God and our journey here on Earth. I also talk to those with cancer and share my journey. I tell them that you have to take it day by day. You can’t start thinking about what-ifs. You have to look at it with a better perspective, with a positive perspective. It’s very easy to get negative about anything. But it won’t do you any good. Think positive thoughts. That’s truly the biggest emotional battle to fight.
My cancer journey has taught me so much. But the most important lesson I learned was to let down my emotional walls. Cancer has given me self-confidence, and now with my walls down, I am trusting God fully to guide me. I am “all in.”
I am grateful for every moment, and I enjoy spending time with my wife, children and three grandchildren, who are the center of my universe. I know I am blessed to be here, and I am going to make the most of my days.
Diagnostic and therapeutic management of esophageal cancer is a multidisciplinary challenge. Male to female ratio in our patients was 1.6 to 1. This proportion is reported in other similar studies.
The most involved part of the esophagus was the middle third, and SCC was the most prominent type. While, in Western countries, the distal third is involved most, maybe the higher incidence of adenocarcinoma, and its potentiality to appear in the distal part can explain this discrepancy. Among 39 recruited cases, 25 (64%) reported a relief in dysphagia. One grade decrease in dysphagia was seen in 46.2% and 2 grade in 17.9%.
In a study in France, a total of 120 patients treated in a single center by insertion of SEMS (Self-expanding Metal Stent), dysphagia scores decreased in 89.1% of patients, with median scores decreasing from 3.0 to 1.0 (P < 0.05). In the present study, mean dysphagia score in the first follow-up decreased significantly compared to pre-operation (from 3.37 to 2.43). Mean survival time after procedure was 177 d (5.9 mo) in recovered group, and 60.7 d (2 mo) in the other group, which was much lower than reported in other studies.
In a study in the Netherlands (2006), data from 78 patients, rendered incurable at exploration, and who subsequently underwent palliative interventions, were analyzed retrospectively. Overall, intraluminal stenting was the palliative measure of dysphagia in 25 patients (32.3%). The median survival in the whole group was 8.9 (1-105) mo. Patients treated with chemotherapy had a higher median survival of 11.6 mo compared to that of the other palliatively-treated patients: 8.4 mo (P = 0.003). They concluded that patients with incurable oesophageal carcinoma have a poor overall survival of less than 9 mo.
In India (2006), thirty patients with inoperable esophageal carcinoma were treated with SEMS. Quality of life score improved significantly from 62-94 before stenting to 80-133 after the procedure. There was improvement in dysphagia grades. Pain was the most common complaint noted on follow up. There was no major morbidity or mortality related to the procedure.
In the present study, no complaints were reported immediately after procedure and in the next follow-up, except for the seven cases that reported aggravation or no recovery of dysphagia. One important and disappointing result of this investigation was the high mortality rate of esophageal cancer in our area. Seven deaths occurred between procedures until the first follow-up (one-month later) and at the end of the study, only 6 cases were alive. Ross et al (USA, 2007) studied ninety-seven patients with malignant dysphagia who had SEMS placed from 2000 to 2003. Dysphagia scores improved in 86%. Early unexpected deaths occurred in 2 patients. Adenocarcinoma and female sex were factors associated with increased odds of a major complication. Median survival was 77 d.
In the present study, dysphagia aggravation and re-dilation was implicated in 7.7%. This is a usual problem seen in all other investigations. In a study in Norway (2006), 37 patients with unresectable esophageal and cardial carcinoma treated with SEMS (January 1997- May 2004) were retrospectively analyzed. One patient died the day the stent was introduced. The median time to repeated hospital contact was 25 d, most often due to recurrence of dysphagia. Ten patients underwent repeated stent insertion. The median survival time after the first stent insertion was 88 d.
In an Italian report (2007), in 60 cases with malignant dysphagia due to the various etiologies stent insertion was done. The mean dysphagia score of 2.8 improved to a mean score of 1.0 after stenting (P < 0.001). Overall median survival time was 4.6 mo. In Germany (2007), stent insertion was done in eighteen patients with esophageal carcinoma. Seventeen of 18 stents were placed technically successful in a single endoscopic procedure. Mean dysphagia score improved from 2.2 to 0.6. In 10 patients, a re-intervention was necessary mainly due to dislocation of the stent.
Although placement of a stent is technically feasible, its application is hampered by frequent stent migration and insufficient prevention of gastroesophageal reflux. Further technical improvements of stents or alternative methods like brachytherapy are required for satisfactory palliation of malignant gastroesophageal stenosis.
Comparing dilation and stenting in the present survey showed that dysphagia recovered in 63.6% after dilation and in 75% after stent insertion.
Although, dysphagia relief and median survival rate were lower in our study, maybe due to the delay in referring and the developed stages at the presentation; however, it seems that palliative care is effective in relieving dysphagia of inoperable esophageal carcinoma, and is suggested for increasing quality of life in the remaining life-span of the patients.
Implantation of stents proved to be an effective and safe method in palliating severe dysphagia in patients with obstructing esophageal cancer; but dilation seems more popular especially in our area; while stents are more expensive, and dilation is more preferred by patients and physicians.
Larger studies with higher sample size and facilities for screening in the lower dysphagia stages and evaluating other factors that impact on the survival rate of the patients are necessary.
Accurate and expanded results could not be achieved in the present report, due to the unavailability of some data and deaths occurred between the procedure and the first follow-up. Also, all included patients had grade 3 and 4 dysphagia, which can itself have an important impact on survival rate, because of prolonged inability of swallowing and the resulting malnutrition.
Esophageal Cancer: A Disease on the Rise
Esophageal cancer is an aggressive form of cancer, and one that often remains asymptomatic until relatively late in the disease process. “Before I was diagnosed with this, I had never heard of it,” says Bart Frazzitta, from Manalapan, New Jersey. “I didn’t even think you could get esophageal cancer.” In fact, there were approximately 14,250 new cases of esophageal cancer diagnosed in 2004 in the United States and 13,300 deaths from the disease. Additionally, of all the solid tumors, esophageal cancer is the one that has been increasing most rapidly in recent years. The reasons for the increase may be related to an increase in gastroesophageal reflux disease and other lifestyle factors.
Esophageal cancer initially develops in the esophagus, which is the smooth muscular tube that carries food and liquids from the throat to the stomach. There are two types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. Squamous cell carcinoma occurs when the cells that normally line the inside of the esophagus begin to proliferate abnormally. Adenocarcinoma develops from abnormal glandular cells that line the walls of the esophagus that has been damaged by gastroesophageal reflux disease (GERD).
Previously, squamous cell carcinoma was the predominant form of the disease. In recent decades, however, adenocarcinoma has become more prevalent and now accounts for more than half of all cases of esophageal cancer in the United States, says Stuart Spechler, MD, from the University of Texas Southwestern Medical Center in Dallas.
Unfortunately, the disease does not produce many symptoms in its early stages and thus goes undetected. Large, advanced tumors may cause weight loss, difficulty swallowing, or evidence of blood in stool or vomit.
With no early warning symptoms, individuals often don’t realize something serious is going on until they have advanced cancer. Frazzitta’s only symptom was chronic heartburn a couple of times a week for about a year. Yet when he was diagnosed in December 1999, he had stage 3 cancer, which means the disease had already spread from the esophagus to surrounding tissues or lymph nodes.
“A lot of people will go and get an antacid and feel better and think they have cured the problem,” says Frazzitta, who subsequently has become a patient advocate and co-founder of the Esophageal Cancer Education Foundation (www.fightec.org). In truth, the antacid just masked a symptom of a serious disease, which is why experts recommend that if heartburn or indigestion persists, people should see a doctor.
The two types of esophageal cancer occur with different frequencies in different ethnic groups. Squamous cell carcinoma is more common in blacks and Asians, while white men are at highest risk for adenocarcinoma.
Some of the risk factors for the two subtypes are the same, but not all of them. For example, obesity is a risk factor for adenocarcinoma, while malnutrition puts individuals at increased risk for squamous cell carcinoma. However, heavy smoking and age over 50 are associated with an increased risk of both types of disease.
Sometimes, however, even those risk factors don’t apply. Vickie Powell, a resident of Radcliff, Kentucky, was just 38 when she developed a case of the hiccups that she couldn’t keep at bay. Initially her doctor put her on an antacid, which she took for a week and a half.
“You know your own body,” says Powell. “I went back to the doctor and said something just is not right.” After more tests, she was told that she had a golf ball-sized tumor in her lower esophagus and upper stomach. She wasn’t overweight, she didn’t drink or smoke, and she doesn’t ever remember having heartburn.
A major risk factor for adenocarcinoma of the esophagus is Barrett’s esophagus, which occurs when the valve that lies between the stomach and the esophagus doesn’t function properly. Normally, it acts like a one-way gate, letting food and liquid move from the esophagus into the stomach, but keeping the acid and digestive enzymes of the stomach in the stomach. If the valve weakens, then acid will escape into the esophagus, which is called acid reflux. Repeated exposure to the acid damages the esophageal cells, causing them to die.
When new cells arise to take their place, a strange thing happens, says Dr. Spechler, who is an expert on Barrett’s esophagus. Instead of regenerating new esophageal cells that would continue to be damaged by the acid escaping from the stomach, the esophagus begins to produce cells that resemble those that line the intestinal tract. Such cells are ready for an acid bath and aren’t damaged as easily by acid reflux.
Unfortunately, these cells are predisposed to form cancers when they arise in the esophagus. Thus, patients with chronic GERD and who develop Barrett’s esophagus are at significantly higher risk for esophageal cancer and should undergo regular cancer surveillance. One common form of surveillance is called endoscopy, in which a physician runs a thin tube with a camera and a light at the end into the esophagus, allowing for a visual of what the tissue looks like.
Screening all GERD patients with endoscopy to look for Barrett’s esophagus is neither feasible nor practical, however. Approximately 60 million adults in the United States have regular heartburn, but only a tiny fraction of those will develop esophageal cancer. Researchers are trying to identify better ways to diagnose esophageal cancer earlier.
Like many cancers, the timing of diagnosis is critical in esophageal cancer. “If we can catch it early, we can cure it,” says Dr. Spechler. With that in mind, physicians like to closely follow patients who have Barrett’s esophagus or other high-risk factors for the disease.
If the cells in the esophagus begin to look abnormal but are not yet cancerous, a stage called dysplasia, Dr. Spechler and others will often recommend surgical treatment to prevent full-blown cancer from developing. If left untreated, 31 to 59 percent of patients with high-grade dysplasia will develop cancer within five years.
Currently, the standard surgery for high-grade dysplasia is an esophagectomy, in which the surgeon removes the unhealthy portion of the esophagus and possibly some of the neighboring stomach, and then reconnects the remaining regions of the tube together. Although this surgery is effective at preventing the disease and treating some stages of the cancer itself, it is a difficult surgery and between 3 and 12 percent of patients may die as a result of the surgery itself.
Researchers are testing less drastic surgical methods, but these are still in clinical trials, and it is not yet clear how effective they are at preventing the development of cancer, although early results look promising. One method involves using an endoscope with a small blade attached to the end to cut away the unhealthy cells. Another method being tested is to use a laser to burn away the dysplastic cells.
For those patients who are diagnosed with esophageal cancer, esophagectomy is the standard therapy, unless the cancer has spread beyond the esophagus and adjacent tissue. The proportion of esophageal cancer patients alive five years after diagnosis is between 5 and 30 percent, depending on the stage of cancer they have at diagnosis and how well they respond to treatment.
Most patients with localized esophageal cancer (stage 1 or 2 disease) used to be treated with surgery alone. In recent years, a combination of chemotherapy and radiation or chemotherapy and radiation followed by surgery is being used more often to treat esophageal cancer, says David Ilson, MD, from Memorial Sloan-Kettering Cancer Center in New York. The addition of chemotherapy to a radiation treatment protocol can enhance the effectiveness of radiation and increase the proportion of patients who achieve a complete remission or a good partial remission with radiation. Subsequent surgery, done after chemotherapy and radiation, can then be used to remove any residual cancer. Combining chemotherapy, radiation therapy and surgery (called combined modality approaches) are increasing the cure rate of this cancer.
The current standard chemotherapy given with radiation therapy is a combination of 5-FU plus cisplatin, but this can lead to significant side effects of mouth sores and esophagitis. “We are trying to identify more effective chemotherapy regimens that have fewer side effects,” says Dr. Ilson.
Regimens currently being tested use cisplatin in combination with newer chemotherapy drugs like Camptosar® (irinotecan), Taxotere® (docetaxel), Taxol® (paclitaxel) and Gemzar® (gemcitabine). Since cisplatin causes a number of side effects, including nausea, vomiting, kidney damage and hearing loss, a better-tolerated analogue of platinum oxaliplatin (Eloxatin™) is being studied in esophageal cancer.
For patients with metastatic (stage 4) disease, surgery is not recommended. Rather, physicians treat such advanced disease with chemotherapy, which is not likely to cure the cancer but may slow its progress and make the patient more comfortable.
Chemotherapy drugs that are used include 5-FU, cisplatin, Taxol, Taxotere, Camptosar and Eloxatin. Additionally, a phase III randomized trial in the United Kingdom is testing the efficacy of a Xeloda® (capecitabine) combination in esophageal cancer. But Dr. Ilson says Xeloda is not yet used frequently in the United States for this disease.
In addition to traditional chemotherapy agents, physicians are testing the use of newer, less toxic targeted drugs in esophageal cancer. Unlike standard chemotherapy drugs, which kill all dividing cells, targeted therapies block specific steps in the cancer cell growth pathway and leave most healthy cells undamaged.
Dr. Ilson’s research group is setting up trials to test the monoclonal antibody Erbitux™ (cetuximab), which targets the epidermal growth factor receptor (EGFR), in combination with standard chemotherapy in patients with locally advanced esophageal cancer. They will also test Avastin® (bevacizumab), another monoclonal antibody that blocks blood vessel formation, in combination with chemotherapy and radiation in adenocarcinoma-type esophageal cancer.
Patients with advanced esophageal cancer may experience difficulty swallowing and an inability to take solid food, which can cause malnourishment and an inability to tolerate chemotherapy. In patients who are not candidates for curative surgery or radiation-based treatment, the relief of swallowing difficulties is a primary goal of palliative or symptom-relieving management. Chemotherapy alone in advanced disease may relieve swallowing problems.
Additionally, there are several options for local therapy, and esophageal stenting is one of the most common. During the procedure, a physician uses endoscopy to place a stent in the esophagus, and, because the stent is a semi-rigid tube, it prevents the tumor from blocking or narrowing the esophagus.
Another option that is sometimes used is called photodynamic therapy. In photodynamic therapy, the patient receives an injection of a drug called Photofrin® (porfimer sodium) that causes cells to be sensitive to light. The gastroenterologist uses an endoscope to then shine laser light on the tumor, killing the cancer cells. One problem with this approach is that the patient has to avoid light for several weeks after treatment, which can significantly lower his or her quality of life. Also, the results of this treatment are relatively short-lived.
If a patient has failed chemotherapy or they have a stent in place but the tumor is overgrowing the stent, physicians may use radiation to locally control the tumor. In some cases, the doctor may opt to use laser therapy in which a laser is attached to an endoscope to kill off parts of the tumor that are causing swallowing difficulties. In this situation, however, radiation is used more frequently than lasers, says Dr. Ilson.
For patients who are malnourished and not able to take in adequate amounts of calories, a feeding tube is placed in the stomach. This tube (usually called a PEG tube) allows food to be administered directly into the stomach, thus ensuring the patient receives adequate nutrition.
Until less toxic treatments are available, the emotional and physical cost of therapy can be high. For example, Powell had an esophagogastrectomy in which the surgeons removed one-fifth of her stomach, 8 inches of her esophagus, the surrounding lymph nodes and the sphincter muscle that controls flow between the esophagus and the stomach. Additionally, because she was so young, her doctor wanted to use a particularly aggressive therapy to prevent recurrence. Thus, after surgery, she received two rounds of chemotherapy, with each round consisting of five days of continuous intravenous drip of 5-FU and cisplatin. She also had 30 radiation treatments.
Now, as she has just had her seventh-year CT scan, she remains cancer-free, though she suffers from surgery complications. Without a sphincter muscle, she still has trouble keeping food down and has to eat small meals every couple of hours rather than three normal-sized ones. And even the small ones make her nauseous. “For a while I was really depressed about it, but I have learned to deal with it. This is what I have left. But I am cancer-free and I try to move on every day,” she says. “Sometimes I don’t realize how lucky I am until I go to the doctor and I tell my story. Now, I’m just at a point where I want to help as many people as I can.”
Frazzitta, who participants can meet at the CURE Patient & Survivor Forum in Washington, D.C., this July, had six weeks of Taxol and cisplatin chemotherapy plus radiation to treat his stage 3 disease. After recovering from this therapy for two months, he underwent an esophagogastrectomy in which the surgeon removed two-thirds of his esophagus and one-third of his stomach. He left the hospital 10 days later.
That was May 2000. Now, nearly five years later he won’t say he’s cancer-free, but his last CT scan six months ago was clear—and he hopes the next one will be clear as well.