Appropriate Timing of Surgery After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

Not Applicable

Completed

• Conditions: Neoplasm, Rectum
• Interventions: Procedure: Total mesorectal excision before 56 days (4-8 weeks); Procedure: Total mesorectal excision after 56 days (8-12 weeks)

• Registration Number: NCT03287843
• Lead Sponsor: Ege University

Brief Summary

This study aimed to compare the outcomes of early versus late surgical resection in patients who underwent curative total mesorectal excision after neoadjuvant chemoradiation. Half of the participants will undergo surgery before 8 weeks, while the other half will undergo surgery after 8 weeks.

Detailed Description

Not available

Study Timeline

• Study Start: 2006-01-01
• Primary Completion: 2017-01-01
• Study First Submitted: 2017-09-13
• Study First Submitted QC: 2017-09-17
• Study First Posted: 2017-09-19
• Results First Submitted: 2019-02-08
• Results First Submitted QC: 2019-07-21
• Results First Posted: 2019-08-29
• Study Completion: 2022-01-01
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-22
• Last Update Posted: 2022-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

1. Clinic stage II-III cancer ( T3- T4 tm or/and N(+) disease )
2. Patients with histologically confirmed adenocarcinoma of the rectum
3. Tumor distal border located within 15 cm. from anal verge (as measured by rigid rectoscopy)
4. Standardized total mesorectal excision surgery
5. Tumor must be clinically resectable with curative intent (R0 resection must be most likely)
6. Elective operation
7. The patient must consent to be in the study and the informed consent must be signed

Exclusion Criteria

1. Clinic stage I and IV cancer disease
2. Patients with malignant disease of the rectum other than adenocarcinoma
3. Recurrent rectal cancer
4. Emergency cases (Mechanical bowel obstruction, perforation)
5. Other previous or concurrent malignancies
6. Any contraindication for radiochemotherapy
7. Previous chemotherapy or radiotherapy to the pelvis
8. Tumor has arisen from chronic inflammatory bowel disease or hereditary polyposis disease
9. American Society of Anesthesiologists Score >3 patients

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Early surgery group	Total mesorectal excision before 56 days (4-8 weeks)	İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy.
Late surgery group	Total mesorectal excision after 56 days (8-12 weeks)	İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy.

Primary Outcome Measures

Name	Time	Method
Pathological Complete Response Rate	2 months	Complete pathological response, defined as the absence of viable tumor cells, may develop after neoadjuvant treatment for rectal cancer. Prognostic factors affecting pathological complete response will be evaluated.

Secondary Outcome Measures

Name	Time	Method
Disease-free Survival	5 years after surgery	Recurrence free survival
Overall Survival	5 years after surgery	Total survival with or without disease
Tumour Regression Grade	30 days after surgery	All pathological examinations were undertaken by two experienced gastrointestinal pathologists. Pathological treatment response to neoadjuvant chemoradiotherapy was evaluated by a five-tiered system described by Mandard.; Tumor regression grade groups were identified as: Grade 1: the absence of residual cancer Grade 2: the presence of residual cancer cells scattered throughout the fibrosis Grade 3: an increase in the number of residual cancer cells but fibrosis still predominant Grade 4: residual cancer outgrowing fibrosis Grade 5, the absence of regressive changes; Grade 1 considered as complete response. Grade 2-4 considered as partial response and Grade 5 considered as no response.
Surgical Complications	90 days after surgery	Morbidity will be assessed according to the classification of Clavien-Dindo as follows: Grade 1: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions. Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgetics, diuretics, electrolytes, and physiotherapy. This grade also includes wound infections opened at the bedside Grade 2: Requiring pharmacological treatment with drugs other than such allowed for grade I complications. Blood transfusions and total parenteral nutrition are also included.; Grade 3: Requiring surgical, endoscopic or radiological intervention (Grade 3a: Intervention not under general anesthesia, Grade 3b: Intervention under general anesthesia) Grade 4: Life-threatening complication requiring Intensive Care Unit management (Grade 4a: Single organ dysfunction (including dialysis), Grade 4b: Multiorgan dysfunction) Grade 5 Death
Completeness of the Mesorectal Dissection	30 days after surgery	Examination will be made in a fresh state for completeness of the mesorectal dissection and will be graded according to the criteria of Quirke as follows: Low: (Grade 1) Little bulk of the mesorectum with defects down into the muscularis propria and/or very irregular circumferential resection margin.; Moderate: (Grade 2) Moderate bulk of the mesorectum but there is irregularity in the mesorectal surface. Moderate coning of the specimen toward the distal margin. At no site is the muscularis propria visible with exception of the insertion of the levator muscles. Moderate irregularity of the circumferential resection margin.; High: (Grade 3) Intact mesorectum with smooth mesorectal surface. No defect deeper than 5 mm. No coning on the specimen. Smooth circumferential resection margins on slicing.
Recurrence	5 years after surgery	Both pelvic recurrence and distant metastasis will be assessed.