Both the character of esophageal cancer and its treatment appear to be changing, although the outlook for long-term survival from this disease, which is usually diagnosed late, remains grim, according to investigators at the recent 9th International Congress on Anti-Cancer Treatment in Paris.
Five-year survival is at best only about 30%, the investigators said, although this is an improvement upon the 5% 5-year survivals commonly seen before combined chemotherapy/radiotherapy trials began about 20 years ago.
The common histology of the tumor also appears to be changing from squamous cell cancer to more adenocarcinomas. Why this is so is "a hundred dollar question. We need more epidemiologic studies," said Muhyi Al-Sarraf, M.D., clinical professor at both Wayne State University, Detroit, and the University of Michigan, Ann Arbor. Al-Sarraf said the only available data are from cooperative group studies.
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Reflux Link
Investigators agree that there are probably environmental factors involved, since the incidence of esophageal cancer varies around the world. In the United States, the increase in esophageal cancer is believed linked to undiagnosed and untreated cases of gastrointestinal reflux.
"I think primary care physicians need to be aware of the increased incidence of adenocarcinoma, particularly in patients with esophagitis, because this cancer is caused by reflux," said Bruce Minsky M.D., a radiologist at Memorial Sloan-Kettering Cancer Center, New York.
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Like early diagnosis, treatment remains somewhat problematic, although investigators reported that radiation treatment alone or chemotherapy alone, whether followed by surgery or not, are now considered out.
In its place is concomitant radio/chemotherapy. Still to be worked out are the best drug combinations and the appropriate dose of radiation. The exact role of surgery is also a subject of controversy.
Ajani, for example, said that the value of chemoradiotherapy in potentially resectable esophageal cancer has not been clearly demonstrated for patients going to surgery because "randomized data do not yet favor the routine use of preoperative chemoradiotherapy."
Al-Sarraf indicated that equivalent results have been achieved with chemoradiotherapy or surgery, raising the question of the need for surgery at all in some patients. "I think it's important that not every patient needs surgery, and can go directly to chemoradiation. The results are the same, but they're not really similar, because we're talking about different patient groups," he said.
In his summary of "where we are," Al-Sarraf said that, "If you look at the literature, there's no survival with chemoradiotherapy that's higher than 30%. And that's exactly what we get with surgery.
"But another thing is that not everyone walking off the street can get surgery. If you look at the University of Michigan, where the patients' weight loss is not great, maybe 80% can go to surgery, but if you go to the hospital literature you don't get more than 40%."
On the other hand, he said, almost everyone can get chemoradiation, "regardless of age, stage [of disease], or performance status." Al-Sarraf added that questions about surgery still need to be answered.
Also important are which chemotherapy and radiotherapy regimens are best for improving survival, according to investigators.
Minsky cautioned that some studies have used super-normal doses, and that fractionation as well as total dose of radiation should be considered.
As for which chemotherapy is best, Minsky said, "I think the standard at this time is a combination of 5-fluorouracil and cisplatin. However there are other combinations being used, such as taxol and cisplatin."
Ajani also mentioned other agents under investigation such as the camptothecins, cisplatin analogs, and pro-drugs of 5-FU. Photodynamic therapy is also under investigation, although it is still deemed highly experimental.
Prevention Is Key
While early diagnosis may be important, the prevention of dysplastic lesions from progressing to cancer as well as the prevention of a recurrence of neoplasia in the aerodigestive tract, is an even more important goal, investigators agreed.
Waun Ki Hong, M.D., of M. D. Anderson, a pioneer in the use of retinoids for prevention of both oral and cervical cancers, said prevention is especially important because of the lack of a major therapeutic breakthrough for esophageal cancer.
In one of his small esophageal cancer studies, Hong noted, about 60% of patients showed reversal of premalignant lesions after being treated with a single retinoid. For the 40% with more advanced lesions who did not respond, he said, about half responded to a combination of a retinoid plus alpha interferon and alpha tocopherol. Examination of several biomarkers showed that clinical response was associated with the elimination of mutated p53 clones.
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