An interventional study of Total mesorectal excision before 56 days (4-8 weeks) and Total mesorectal excision after 56 days (8-12 weeks) in Neoplasm, Rectum, sponsored by Ege University. Completed. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2022-03-31.
Sponsored by Ege University · Not applicable, Interventional, and Treatment
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.
Exclusion Criteria:
İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy.
Procedure: Total mesorectal excision before 56 days (4-8 weeks)
İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy.
Procedure: Total mesorectal excision after 56 days (8-12 weeks)
Low anterior resection or abdominoperineal resection
Low anterior resection or abdominoperineal resection
Pathological Complete Response Rate
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.
Time frame: 2 months
Completeness of the Mesorectal Dissection
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.
Time frame: 30 days after surgery
Tumour Regression Grade
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.
Time frame: 30 days after surgery
Surgical Complications
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
Time frame: 90 days after surgery
Recurrence
Both pelvic recurrence and distant metastasis will be assessed.
Time frame: 5 years after surgery
Disease-free Survival
Recurrence free survival
Time frame: 5 years after surgery
Overall Survival
Total survival with or without disease
Time frame: 5 years after surgery
| Milestone | Classic Interval Group | Long Interval Group |
|---|---|---|
| Started | 175 | 175 |
| Excluded | 12 | 8 |
| Lost to follow up | 3 | 0 |
| Completed | 160 | 167 |
| Not completed | 15 | 8 |
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.
| Participants | Classic Interval Group | Long Interval Group |
|---|---|---|
| Pathological Complete Response Rate | 16 | 31 |
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.
| Participants | Classic Interval Group | Long Interval Group |
|---|---|---|
| Low | 5 | 8 |
| Moderate | 11 | 10 |
| High | 144 | 149 |
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.
| Participants | Classic Interval Group | Long Interval Group |
|---|---|---|
| Mandard Grade 1 | 16 | 31 |
| Mandard Grade 2 | 37 | 36 |
| Mandard Grade 3 | 73 | 67 |
| Mandard Grade 4 | 31 | 29 |
| Mandard Grade 5 | 3 | 4 |
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
| Participants | Classic Interval Group | Long Interval Group |
|---|---|---|
| Clavien Dindo 1 | 4 | 7 |
| Clavien Dindo 2 | 15 | 14 |
| Clavien Dindo 3a | 4 | 3 |
| Clavien Dindo 3b | 8 | 2 |
| Clavien Dindo 4a | 4 | 2 |
| Clavien Dindo 4b | 0 | 1 |
| Clavien Dindo 5 | 1 | 4 |
| No complication | 124 | 134 |
Both pelvic recurrence and distant metastasis will be assessed.
Results for this outcome have not been posted.
Recurrence free survival
Results for this outcome have not been posted.
Total survival with or without disease
Results for this outcome have not been posted.
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Classic Interval Group | 1/160 (0.6%) | 36/160 (22.5%) | 0/160 (0%) |
| Long Interval Group | 4/167 (2.4%) | 33/167 (19.8%) | 0/167 (0%) |
| Event | Classic Interval Group | Long Interval Group |
|---|---|---|
| Wound infectionSurgical and medical procedures | 6/160 | 9/167 |
| Prerenal insufficiencyRenal and urinary disorders | 5/160 | 4/167 |
| Mechanical bowel obstructionGastrointestinal disorders | 5/160 | 4/167 |
| Anastomotic leakageGastrointestinal disorders | 4/160 | 4/167 |
| OtherSurgical and medical procedures | 4/160 | 0/167 |
| Urinary tract infectioRenal and urinary disorders | 3/160 | 2/167 |
| PneumoniaRespiratory, thoracic and mediastinal disorders | 1/160 | 3/167 |
| Postoperative bleedingSurgical and medical procedures | 2/160 | 2/167 |
| AtelectasisRespiratory, thoracic and mediastinal disorders | 2/160 | 1/167 |
| Deep vein thrombosis, pulmonary embolismVascular disorders | 2/160 | 2/167 |
350 patients were randomly assigned. After perioperative evaluation of 350 patients who underwent CRT , 15 patients in the CI group (no surgery, 5; R2 resection, 5; stage IV disease, 2; lost to follow-up, 3) and eight in the LI group (no surgery, 4; R2 resection, 2; stage IV disease, 2) were excluded from the study. 327 included in the analysis.
| Age, Continuous(years) | Classic Interval Group | Long Interval Group | Total |
|---|---|---|---|
| Mean | 60.4 (22 to 85) | 61.7 (32 to 85) | 61.0 (22 to 85) |
| Sex: Female, Male(Participants) | Classic Interval Group | Long Interval Group | Total |
|---|---|---|---|
| Female | 65 | 71 | 136 |
| Male | 95 | 96 | 191 |
No study locations are listed for this record.
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Ege University