Clinical trial NCT01609504: ELRR by TEM Versus Laparoscopic TME in iT2N0M0 SMALL LOW RECTAL CANCER
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rectal Cancer
Keywords: Rectal cancer
Radiochemotherapy
Transanal Endoscopic Microsurgery
Laparoscopic Resection
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
Collaborators: name: Università Politecnica delle Marche
First posted: 2012-06-01
Enrollment: 283
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: oncological result in term of local and/or systematic recurrence
timeFrame: 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 42, 48, 54, 60 months after operation
Secondary outcomes:
measure: Morbidity
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 3 and 6 days each group
measure: operative time
timeFrame: operative time
measure: blood loss
timeFrame: during time of operation
measure: analgesic use
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 3 and 6 days each group
measure: 30 day mortality
timeFrame: at 30 days from operation
measure: hospital stay
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 3 and 6 days each group
measure: cancer-related mortality
timeFrame: 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 42, 48, 54, 60 months after operation
Other outcomes:
Locations:
Study officials:
affiliation: university Sapienza of Rome, Italy
name: Emanuele Lezoche, Pr
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.