Abstract
Abstract
Background: Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications.
The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas.
Methods/design: Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma ≥ 3 cm, located between 1–15 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane in a piecemeal fashion, and patients will be discharged from the hospital. Residual adenoma that is visible during the first surveillance endoscopy at 3 months will be removed endoscopically in both treatment strategies and is considered as part of the primary treatment.
Primary outcome measure is the proportion of patients with recurrence after 3 months. Secondary outcome measures are: 2) number of days not spent in hospital from initial treatment until 2 years afterwards; 3) major and minor morbidity; 4) disease specific and general quality of life; 5) anorectal function; 6) health care utilization and costs. A cost-effectiveness and cost-utility analysis of EMR against TEM for large rectal adenomas will be performed from a societal perspective with respectively the costs per recurrence free patient and the cost per quality adjusted life year as outcome measures.
Based on comparable recurrence rates for TEM and EMR of 3.3% and considering an upper-limit of 10% for EMR to be non-inferior (beta-error 0.2 and one-sided alpha-error 0.05), 89 patients are needed per group.
Discussion: The TREND study is the first randomized trial evaluating whether TEM or EMR is more cost-effective for the treatment of large rectal adenomas.
Background
Rectal cancer is a common disease in the Netherlands with approximately 4,000 new cases and 2,000 deaths annually. The incidence of rectal cancer increases with age, male sex and obesity, without ethnic preference. In the pathogenesis, premalignant intraepithelial neoplasia that is located in a rectal adenoma, precedes the occurrence of invasive rectal cancer. Early endoscopic detection and removal of rectal adenomas prevents the development of rectal cancer and is therefore the most reliable contributor to the 'cure' of this disease. When rectal adenomas become large, however, standard endoscopic therapies like simple loop polypectomy or one-step endoscopic resection will be inadequate. Therefore, large rectal adenomas must be removed either surgically or by extended endoscopic mucosal resection (EMR).
In 1984 a novel surgical approach for the resection of large rectal adenomas has been introduced in Germany: transanal endoscopic microsurgery (TEM). This procedure encompasses general anesthesia, the use of expensive specialized equipment, a full-thickness rectal wall excision and hospital admission. Since its introduction, many surgical practices (including the Netherlands) have adopted TEM as the new standard therapy for large rectal adenomas. Alongside the introduction and refinement of TEM for rectal adenomas, advanced endoscopic therapies like extended EMR have rapidly evolved. For extended EMR no sedation, no sophisticated equipment and no hospital admission are required as opposed to TEM. Furthermore, only the neoplastic mucosa is resected instead of the full-thickness rectal wall, having a potential benefit of fewer complications.
Supporters of the TEM technique praise the excellent exposure of the rectum and the minimal invasiveness, as opposed to conventional surgical techniques. Besides, recurrence rates after TEM appear to be lower when compared to conventional surgical transanal excision. The TEM technique has shown to be highly efficacious in several retrospective and prospective case series with reported recurrence rates of 0–19% and complication rates of 2–21%.
On the other hand, extended EMR has gained more and more support in the last few years, mainly due to good clinical results after EMR in the esophagus and stomach. Endoscopic mucosal resection has also been described for the treatment of large colorectal adenomas, revealing recurrence rates of 0–9% and complication rates of only 0–9%. In case adenomas can not be removed completely during one EMR attempt, repeat EMR for residual disease generally leads to an overall success rate of 96–100%. Recently, the first prospective study analyzing extended EMR for large rectal adenomas has been described, revealing a recurrence rate of 8% and complication rate of 8%. In this study, all recurrences were detected during the first control endoscopy after 3 months; repeat EMR of residual disease led to an overall success rate of 98.4%.
Since the efficacy of extended EMR for large rectal adenomas appears to be comparable to TEM, we started a prospective registration of patients with large non-pedunculated rectal adenomas who were treated by EMR in the Academic Medical Center Amsterdam. Preliminary results of this study were published in form, demonstrating that EMR is safe and effective for the resection of large rectal adenomas having an overall success rate so far of 100%.
Until now, TEM and EMR have never been formally compared, and no such comparative studies have been registered at this moment. Although selection bias inevitably exists in prospective and retrospective case series, the results of these studies suggest that both TEM and EMR have comparable recurrence rates. Even when recurrences occur after TEM or EMR, most of these can successfully be re-treated without the need for radical surgery. The literature furthermore suggests that EMR is associated with fewer complications, reduced hospital admission, and no general anesthesia is required for EMR, all of which are favorable in both patients' and societal perspective. These contrasts of the two procedures might well lead to differences in costs and quality of life. Therefore, we designed a multicenter randomized trial to compare TEM and EMR for the resection of large rectal adenomas. The main objective of this study will be a cost-effectiveness and cost-utility analysis of these two procedures.