ELRR by TEM Versus Laparoscopic TME in iT2N0M0 SMALL LOW RECTAL CANCER (ELRRvsLTME)

Randomized Controlled Clinical Trial: Endoluminal Loco-regional Resection (ELRR) by Transanal Endoscopic Microsurgery (TEM) Versus Laparoscopic Total Mesorectal Excision (LTME) in it2n0m0 Small Low Rectal Cancer

The present prospective randomized study investigated the results of ELRR (ENDOLUMINAL LOCO-REGIONAL RESECTION BY TRANSANAL ENDOSCOPIC MICROSURGERY) versus LTME (LAPAROSCOPIC TOTAL MESORECTAL EXCISION) in the management of 100 patients with iT2N0M0 small low rectal cancer after Neoadjuvant Treatment.

Study Overview

• Status: Completed
• Conditions: Rectal Cancer
• Intervention / Treatment: Procedure: ELRR BY TEM; Procedure: LTME

Detailed Description

From April 1997 to April 2004, patients with cT2 rectal cancer and no suspicion for positive lymph-nodes or distant metastases (cN0 M0) were enrolled in this study.

History, routine laboratory tests including tumour markers, digital examination to evaluate tumour fixation and sphincter tone, clinical evaluation, were recorded for each patient in a data base.

At admission, staging included: 1) endorectal ultrasound (EUS) 2) rigid rectoscopy and tumour biopsies; 3) total colonoscopy with vital dye staining of the rectum and 6-8 standard biopsies of normal mucosa at a distance of approximately 1 cm around the tumour with India ink tattooing of biopsy sites; 4) helical Total Body Computerized Tomography (CT), and 5) pelvic magnetic resonance imaging (MRI). Rigid rectoscopy was performed in order to measure the exact distance of the tumour from the anal verge and to select the most appropriate patient's position on the operative table in case of TEM surgery.

Positive lymph-node status at imaging was established according to the following criteria:

1. at EUS, diameter > 0.8 cm, circular or irregular shape, hypervascularization at colour Doppler and hypoechogenicity.
2. at CT and MRI, diameter of > 0.8 cm, circular or irregular shape. All patients with suspicious nodes or contradictory response at EUS, CT or MRI T staging were not enrolled in the present study.

Inclusion criteria were: tumour located within 6 cm from the anal verge, tumour diameter not larger than 3 cm, and staged as cT2 N0 M0, G1-2. Patients classified as American Society of Anaesthesiologists (ASA) 3 or 4 were excluded.

All patients underwent preoperative radiotherapy. The total dose given was 50.4 Gy in 28 fractions over 5 weeks. The irradiated areas were: anus, rectum, mesorectum, regional and iliac lymph-nodes. Continuous infusion of 5-FU 200 mg/m2/day was performed during radiotherapy treatment.

Forty days after the end of NT, staging as described above (except for total colonoscopy) was repeated. Downsizing was classified in two groups: patients with tumour mass reduction more than 50% (responders) and patients with tumour mass reduction less than 50% (low or non responders). According to the study protocol, patients with disease progression were excluded.

Randomization was performed the day before operation. Patients were stratified in two groups and subsequently allocated 1:1 to the two arms of the study, ELRR by TEM (arm A) or LTME (arm B) by means of sealed opaque envelopes containing computer-generated random numbers. In the end, 50 patients underwent ELRR by TEM (arm A) and 50 patients underwent laparoscopic resection (LTME) (laparoscopic low anterior resection or abdominal-perineal resection) (arm B). The recruitment was interrupted when 100 patients had undergone operation.

Surgery was performed between 45 and 55 days after the end of radio-chemotherapy. Preoperative washout of the colon (polyethyleneglycol) and short-term antibiotic prophylaxis (metronidazole and second generation cephalosporin) were administered to all patients. Surgical procedures were performed only by two surgeons expert in open rectal surgery and skilled in both laparoscopic and TEM procedures.

TEM procedures were performed with the Wolf Company (Tuttlingen, Germany) instrumentation. The surgical technique of ELRR was as follows: mucosal incision included all the tattoo spots performed at admission staging, in order to excise a minimum of 1 cm of normal mucosa around the tumour, according to its diameter before NT. Starting from the mucosal incision the dissection was continued deeply in order to remove all the mesorectum adjacent to the tumour, following a cutting line with an angle of approximatively 120-135° with respect to the mucosal plane. For posterior and lateral lesions the bottom dissection plane was carried down to the "holy plane" and for anterior lesions to the level of the vagina septum or the prostatic capsule. In case of tumour with the distal limit at the level of the anal canal, the incision included the dentate line and the internal sphincter fibres were partially removed. For distal tumours, in order to maintain the CO2 rectum insufflation it is recommended to adjust the rectoscope axis so as to keep its inferior circumference adherent to the anal canal. In all patients the defect was closed by multiple running stitches, according to the technique described by Buess.

The surgical technique of Arm B was laparoscopic low anterior resection or abdominal perineal resection.

Primary endpoint in this study was the oncological result in terms of local recurrence, distant metastases and cancer related mortality with minimum follow-up time of 5 years. Secondary endpoints were: operative time, blood loss, analgesic use, morbidity, hospital stay and 30 day mortality. Major morbidity was defined as complications requiring surgical treatment. In order to evaluate local and/or systemic recurrence, all patients were prospectively followed-up by clinical examination, tumour markers' assay and rectoscopy every 3 months for the first 3 years, then every six months. Total body CT, and pelvic MRI were repeated every 6 months for the first 5 years. According to the study protocol, no adjuvant therapy was administered, as recommended by the consultant oncologist in T2N0 rectal cancer patients.

• Study Type: Interventional
• Enrollment (Actual): 283
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Tumor located within 6 cm from the anal verge
• Tumor diameter not larger than 3 cm, and staged as iT2, N0, G1-2

Exclusion Criteria:

• Patients classified as American Society of Anaesthesiologists (ASA) 3 or 4

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transanal Endoscopic Microsurgery; Patients were treated by TEM as follows: mucosal incision included all the tatoo spots performed at admission staging, in order to excise a minimum of 1 cm of normal mucosa around the tumor, according to its diameter before NT (ELRR- Endo Luminal Loco Regional Resection)	Procedure: ELRR BY TEM; The surgical technique of ELRR was as follows: mucosal incision included all the tatoo spots performed at admission staging, in order to excise a minimum of 1 cm of normal mucosa around the tumor, according to its diameter before NT; Other Names: FULL-THICKNESS + FAT EXCISION BY TEM
Active Comparator: Total Mesorectal Excision	Procedure: LTME; LAPAROSCOPIC TOTAL MESORECTAL EXCISION INCLUDING MESORECTAL (ACCORDING TO HEALD CRITERIA); Other Names: LAPAROSCOPIC LOW ANTERIOR/ABDOMINO-PERINEAL RESECTION

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
oncological result in term of local and/or systematic recurrence	To evaluate local and/or systematic recurrence, all patients were followed up prospectively by clinical examination, measurement of tumour markers and sigmoidoscopy every 3 months for the first 3 years, and every 6 months thereafter. Whole-body CT and pelvic MRI were repeated every 6 months for the first 5 year. All patients had a minimum follow-up of 5 years.	3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 42, 48, 54, 60 months after operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morbidity	No. of patients with postoperative complications	participants will be followed for the duration of hospital stay, an expected average of 3 and 6 days each group
operative time	operative time (minutes)	operative time
blood loss	blood loss (ml)	during time of operation
analgesic use	No. of patients receiving analgesia	participants will be followed for the duration of hospital stay, an expected average of 3 and 6 days each group
30 day mortality	No. of patients died within 30 days from operation	at 30 days from operation
hospital stay	hospital stay (days)	participants will be followed for the duration of hospital stay, an expected average of 3 and 6 days each group
cancer-related mortality	No. of patients died for cancer. To evaluate local and/or systemic recurrence, all patients were followed up prospectively. After 5 year every 12 months. All patients had a minimum follow-up of 5 years	3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 42, 48, 54, 60 months after operation

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza
• Collaborators: Università Politecnica delle Marche
• Investigators: Principal Investigator: Emanuele Lezoche, Pr, university Sapienza of Rome, Italy

Publications and helpful links

General Publications

• Lezoche E, Baldarelli M, Lezoche G, Paganini AM, Gesuita R, Guerrieri M. Randomized clinical trial of endoluminal locoregional resection versus laparoscopic total mesorectal excision for T2 rectal cancer after neoadjuvant therapy. Br J Surg. 2012 Sep;99(9):1211-8. doi: 10.1002/bjs.8821.

Study record dates

Study Major Dates

• Study Start: April 1, 1997
• Primary Completion (Actual): April 1, 2004
• Study Completion (Actual): April 1, 2004

Study Registration Dates

• First Submitted: September 15, 2011
• First Submitted That Met QC Criteria: May 29, 2012
• First Posted (Estimate): June 1, 2012

Study Record Updates

• Last Update Posted (Estimate): June 1, 2012
• Last Update Submitted That Met QC Criteria: May 29, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Rectal cancer; Radiochemotherapy; Transanal Endoscopic Microsurgery; Laparoscopic Resection
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: URBINO-LEZ-1995