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Improved survival with preoperative chemotherapy for esophageal cancer
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Long-term follow-up data found that preoperative chemotherapy improved survival in patients with operable esophageal cancer, according to a recent study.
The data were reported by William Allum, MD, a surgeon at the Royal Marsden Hospital in England. Allum and colleagues randomly assigned 802 patients with esophageal cancer to surgery alone or surgery with preoperative combination cisplatin and 5-fluorouracil.
The initial results indicated a significant disease-free and overall survival advantage in the group that received chemotherapy plus surgery. These results were reported in 2002 after a median three-year follow-up.
After six years of follow-up, disease-free and overall survival remained significantly higher in the chemotherapy-plus-surgery group. The five-year survival rate in the chemotherapy-plus-surgery group was 23% vs. 17% in the surgery-alone group. The survival difference was similar in both adenocarcinoma and squamous cell carcinoma. – by Emily Shafer
For more information:
- Allum WH, Fogarty PJ, Stenning SP, et al. #9. Presented at: 2008 Gastrointestinal Cancers Symposium; Jan. 25-27, 2008; Orlando.
These results are disappointing. The absolute survival benefit was about 5% for squamous cell carcinoma and 7% for adenocarcinoma, which is a very modest improvement for an adjuvant treatment. The other concern is that even if there was a combined 6% benefit, the mortality from surgery in the trial was 10%. The risk for dying from the surgery was nearly twice as high as the chance of seeing a benefit from chemotherapy.
This and other trials support the use of preoperative chemotherapy in adenocarcinoma, but the same is hard to argue in squamous cell carcinoma. For squamous cancer, many would argue that a combination of chemotherapy and radiation, even without surgery, should be the standard. Surgery for these patients should be reserved for patients who do not respond to chemoradiation.
The data support, at a minimum, preoperative chemotherapy on adenocarcinoma. When you add radiation to preoperative chemotherapy, you tend to get higher rates of complete response, better resection rates and trends toward better survival. The problem is that the phase-3 trials of chemoradiation are small and underpowered, so any modest differences haven’t come out clearly. The preoperative chemotherapy trials accrue many more patients and, thus, can show more modest survival benefits.
In adenocarcinoma of the esophagus, preoperative chemotherapy or chemoradiation are standard treatments. Many in the United States use chemoradiation because of the trends suggesting more benefit. For squamous cancer, preoperative chemotherapy should not represent a standard. Even if there were a lower operative mortality (3% to 5% at major cancer centers), you are still dealing with a survival benefit that is essentially equivalent to the risk for death from the surgery. Many would consider primary chemoradiation the optimal approach for squamous cancer and then selective surgery in patients with residual disease or patients who don’t respond.
We’ve now established that preoperative treatment plays a role in adenocarcinoma. Certainly, a randomized trial testing the role of radiation would be helpful, but that’s always a difficult trial to do. Researchers on a small German trial tried to look at preoperative chemotherapy vs. chemoradiation. The trial did not accrue enough patients, but the data did suggest that radiation improved local control, overall survival and complete response rates.
– David H. Ilson, MD, PhD
HemOnc Today Editorial Board member