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Vigilant surveillance for esophageal carcinoma relapse appropriate after bimodality therapy
Patients with esophageal cancer who experienced local relapse more than 6 months after chemoradiotherapy demonstrated favorable survival outcomes with salvage surgery, suggesting vigilant surveillance is warranted in this setting, according to study results.
Kazuki Sudo, MD, of the department of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, and colleagues sought to evaluate the role of surveillance and the occurrence of relapses in patients with esophageal carcinoma who had been treated with bimodality therapy (chemotherapy and radiation therapy).
The analysis included 276 patients with a median age of 67 years (range, 20-89). All patients underwent bimodality therapy but did not undergo surgery within 6 months of treatment.
Surveillance included visits every 3 months during the first year, every 6 months for the next 2 years, and once a year for the last 2 years.
Median follow-up was 54.3 months.
Overall, 184 patients (66.7%) experienced a relapse. The first sign of treatment failure in these patients included local relapse (n=64; 23.2%), and distant metastasis with or without local relapse (n=120 patients; 43.5%). The final rates for relapse were 14.5% for local relapse only, 15.9% for distant metastasis only, and 36.2% for distant metastasis plus local relapse. A third of patients (n=92; 33.3%) never relapsed.
A majority of local relapses (91%) occurred within 2 years of bimodality therapy, and 98% occurred within 3 years of therapy.
Of the 64 patients who experienced local relapse, 23 (36%) were able to undergo salvage surgery. The median OS for patients who underwent surgery was 58.6 months (95% CI, 28.8 – not reached). Median OS for patients unable to undergo surgery was 9.5 months (95% CI, 7.8-13.3).
“Our data show that, after bimodality therapy, patients with local relapse can undergo salvage surgery and have a decent OS,” Sudo and colleagues concluded. “Approximately 8% of the entire population seems to benefit from surveillance; therefore, vigilant surveillance in patients who have undergone bimodality therapy is recommended, at least during the first 24 months. We draw this conclusion with caution, given that cost analysis was not performed.”
Disclosure: The researchers report research funding or travel expenses from, employment or consultant/advisory roles with, and stock ownership in Abbott Laboratories, Amgen, Boston Scientific, Cook Medical, GlaxoSmithKline, Johnson & Johnson, Mauna Kea Technologies, Olympus, Pfizer and Taiho Pharmaceutical.
Perspective
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Preoperative treatment with either chemotherapy or combined chemoradiotherapy is standard treatment for locally advanced esophageal cancer, and the predominant approach in the United States is the use of combined chemoradiotherapy followed by surgery. The CROSS trial conducted in the Netherlands — which compared esophagectomy alone to preoperative weekly carboplatin, paclitaxel, and radiotherapy followed by surgery — indicated superior survival for preoperative therapy and established encouraging rates of pathologic complete response. Publication of this trial has since led to wide adoption of this therapeutic approach in esophageal cancer treatment. Because of the higher rate of pathologic complete response to chemoradiotherapy in squamous cancers, primary chemoradiotherapy is considered a care standard with the selective application of surgery for patients with biopsy-positive persistent local disease. For adenocarcinoma, primary chemoradiotherapy without surgery is considered for patients less suitable for esophagectomy, including more elderly patients with comorbidities.
Sudo and colleagues from The University of Texas MD Anderson Cancer Center now report a large retrospective series of patients with esophageal cancer treated with primary chemoradiotherapy without surgery. They evaluated the pattern of recurrence, and the frequency and utility of delayed salvage esophagectomy in patients with recurrence more than 6 months after completion of chemoradiotherapy. Squamous cancers accounted for only a minority of patients (21%). Of 276 patients, distant metastatic disease occurred in nearly half of patients (44%), local recurrence only occurred in 23%, and 33% did not develop recurrence. Of the local recurrence only patients, roughly one-third (36%) underwent salvage esophagectomy and achieved an encouraging median survival of 59 months.
This series highlights the need for close follow up and surveillance of patients treated with primary chemoradiotherapy without surgery, for at least the first 2 years after treatment. Some patients with local recurrence only may obtain benefit from salvage surgery (overall 8% of the patient series reported). The high rate of development of metastatic disease supports the potential deferral of surgery in an appropriate patient population.
Would earlier surgery in all of these patients have potentially reduced the high risk of developing metastatic disease? Preoperative chemoradiotherapy trials continue to achieve relatively poor OS (only 30% to 40% at 5 years), arguing that metastatic disease is a large component of therapy failure even when surgery is added to part of primary management.