Randomized phase III trial in locally advanced squamous cell carcinoma (SCC) of the esophagus: chemoradiation with and without surgery

Reviewer: S. Jack Wei, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 2, 2003

Presenter: M Stahl
Presenter's Affiliation: German Oesophageal Cancer Study Group
Type of Session: Scientific

Background

Treatment of locally advanced esophageal cancer remains difficult. Treatment with surgery alone results in overall survival (OS) of less than 15%. Recent studies have demonstrated improved outcomes by combining surgery with chemoradiation. It remains unclear if the addition of surgery to chemoradiation results in improved outcome.

Materials and Methods

Patients were eligible if they had T3-T4, N0-1 squamous cell carcinoma of the esophagus and performance status of 0-1.
Patients were randomized to 2 arms: 1) 3 cycles of 5-FU/leucovorin/etoposide/cisplatin (FLEC) followed by 40 Gy radiation therapy (RT) + etoposide/platinum (EP) followed by transthoracic esophagectomy or 2) Induction FLEC chemotherapy followed by >66 Gy RT + EP.

Results

177 patients were randomized from 1994 to 2002.
Complete resection was acheived in 81% of patiens in Arm 1.
There was no difference in median survival and 3 year OS between the 2 groups (16.3 mo and 30.7% for the surgery arm vs. 15.2 mo and 23.6% for the chemoRT arm, p=0.06)
Improved 3 year local control was seen in patients undergoing surgery (42% vs. 26%).
Patients who recieved surgery were less likely to have local recurrence as first site of failure (64% vs. 81%, p=0.08)
Higher treatment mortality was seen with the surgery arm (10% vs. 3.5%) although this was not statistically significant.
On subgroup analysis, patients who responded to induction chemotherapy had similar 3 yr OS between the two treatment arms (45% vs. 44%); non-responders had 3 yr OS of 18% for the surgery arm vs. 11% for the chemoRT arm.
Non-responders who underwent complete resection had a 3 yr OS of 35%.

Author's Conclusions

The addition of surgery to chemoRT likely results in improved local control.
There is no definite survival advantage to the addition surgery.
A possible subset of patients who did not respond to treatment may benefit from surgery.
Future trials are needed to determine better predictors for response to induction chemotherapy that may help direct subsequent treatment.

Clinical/Scientific Implications

The results of this study fail to show definitive benefit of the addition of surgery to chemoRT in locally advanced esophageal cancer. Although there may be an improvement in local control, this does not translate into a survival advantage and is associated with a higher rate of treatment-related morbidity and mortality. Treatment results for this patient population remains poor, and further studies are needed to identify alternative treatments.

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