SAN DIEGO – An interval between neoadjuvant chemoradiation and esophagectomy that extends beyond 8 weeks is not associated with increased perioperative complications, increased pathological complete response, or change in overall survival, results from a long-term single-center study showed.
"For patients who have not yet recovered from neoadjuvant chemoradiation, it is safe to delay surgery to allow them to improve their performance status," Dr. Jae Y. Kim said at the annual meeting of the Society of Thoracic Surgeons.
Traditionally, he said, surgery has been recommended within 8 weeks after completing neoadjuvant chemoradiation for esophageal cancer, yet many patients choose to delay their surgery.
Some patients have not yet recovered from chemoradiation, while others are delayed for personal or logistical reasons, explained Dr. Kim, a thoracic surgery fellow at the University of Texas M.D. Anderson Cancer Center, Houston. "The impact of this delay on outcomes is unknown." Radiation-induced tumor necrosis increases over time, he said, and there is evidence from rectal cancer that a longer interval may increase the rate of pathological complete response. "On the other hand, there are theoretical concerns that this delay may lead to increased radiation fibrosis and cause a more difficult operation. It is also possible that a delay would allow for tumor regrowth."
In an effort to determine whether an increased interval between chemoradiation and surgery is associated with risk of major perioperative complications or overall survival, Dr. Kim and his associates conducted a retrospective study of 266 patients with esophageal cancer followed by neoadjuvant chemoradiation who were treated at M.D. Anderson in 2002-2008. They divided the patients into two groups: a "short-interval" group of 150 who underwent esophagectomy within 8 weeks of chemoradiation, and a "delayed" group of 116 who underwent esophagectomy more than 8 weeks following chemoradiation.
"Most patients were clustered around 4-11 weeks," Dr. Kim said. "No patient had surgery more than 46 weeks after completing neoadjuvant chemoradiation."
The median interval from completion of neoadjuvant therapy to surgery was 46 days in the short-interval group and 76 days in the delayed group. In both groups, more than 95% of patients were staged with PET-CT and endoscopic ultrasound.
The researchers compared the two groups in terms of perioperative complications, rate of pathological complete response, and overall survival.
The two groups were similar in 18 of 22 baseline characteristics examined, but they were different in four areas. Compared with their counterparts in the short-interval group, the patients in the delayed group were slightly older (mean age, 60 years vs. 57 years, respectively), had more coronary artery disease (17% vs. 7%), had less adenocarcinoma histology (87% vs. 97%), and weighed less (53% with a body mass index of 25 kg/m2 or greater vs. 75% of their counterparts in the short-interval group).
By any objective measure used to gauge the difficulty of the operation, the two groups were similar, including mean OR time (390 minutes in the short-interval group vs. 398 minutes in the delayed group), mean number of lymph nodes removed (21% vs. 20%), and mean estimated blood loss (505 mL vs. 478 mL).
The rates of major complications also were similar between the two groups, including perioperative mortality (2% in the short-interval group vs. 3% in the delayed group), median length of stay (11 days in each group), and rate of anastomotic leak (11% vs. 16%).
The rate of pathological complete response was similar between the two groups (21% vs. 23%).
Overall 5-year survival in the short-interval group was 46%, compared with 36% in the delayed-surgery group, a nonsignificant difference. Disease-free 5-year survival in the short-interval group was 44%, compared with 36% in the delayed group.
"The timing of surgery, both as a continuous and a dichotomous variable, was not associated" with perioperative complication or death, pathological complete response, or overall survival, Dr. Kim added.
On multivariable analysis, older age, more involved lymph nodes, and advanced pathological stage were independently associated with decreased survival.
The researchers performed a subgroup analysis of patients with adenocarcinoma histology and found that the results were similar.
Dr. Kim said that he had no relevant financial disclosures.