Trial Outcomes & Findings for Appropriate Timing of Surgery After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer (NCT NCT03287843)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

350 participants

Primary outcome timeframe

2 months

Results posted on

2022-03-31

Participant Flow

Participant milestones

Participant milestones
Measure	Classic Interval Group İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection	Long Interval Group İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection
Overall Study STARTED	175	175
Overall Study Excluded	12	8
Overall Study Lost to Follow up	3	0
Overall Study COMPLETED	160	167
Overall Study NOT COMPLETED	15	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Classic Interval Group n=160 Participants İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection	Long Interval Group n=167 Participants İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection	Total n=327 Participants Total of all reporting groups
Age, Continuous	60.4 years n=5 Participants	61.7 years n=7 Participants	61.0 years n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	71 Participants n=7 Participants	136 Participants n=5 Participants
Sex: Female, Male Male	95 Participants n=5 Participants	96 Participants n=7 Participants	191 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Classic Interval Group n=160 Participants İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection	Long Interval Group n=167 Participants İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection
Pathological Complete Response Rate	16 Participants	31 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Classic Interval Group n=160 Participants İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection	Long Interval Group n=167 Participants İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection
Completeness of the Mesorectal Dissection Low	5 Participants	8 Participants
Completeness of the Mesorectal Dissection Moderate	11 Participants	10 Participants
Completeness of the Mesorectal Dissection High	144 Participants	149 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Classic Interval Group n=160 Participants İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection	Long Interval Group n=167 Participants İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection
Tumour Regression Grade Mandard Grade 1	16 Participants	31 Participants
Tumour Regression Grade Mandard Grade 2	37 Participants	36 Participants
Tumour Regression Grade Mandard Grade 3	73 Participants	67 Participants
Tumour Regression Grade Mandard Grade 4	31 Participants	29 Participants
Tumour Regression Grade Mandard Grade 5	3 Participants	4 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Classic Interval Group n=160 Participants İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection	Long Interval Group n=167 Participants İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection
Surgical Complications Clavien Dindo 1	4 Participants	7 Participants
Surgical Complications Clavien Dindo 2	15 Participants	14 Participants
Surgical Complications Clavien Dindo 3a	4 Participants	3 Participants
Surgical Complications Clavien Dindo 3b	8 Participants	2 Participants
Surgical Complications Clavien Dindo 4a	4 Participants	2 Participants
Surgical Complications Clavien Dindo 4b	0 Participants	1 Participants
Surgical Complications Clavien Dindo 5	1 Participants	4 Participants
Surgical Complications No complication	124 Participants	134 Participants

SECONDARY outcome

Timeframe: 5 years after surgery

Both pelvic recurrence and distant metastasis will be assessed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 5 years after surgery

Recurrence free survival

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 5 years after surgery

Total survival with or without disease

Outcome measures

Outcome data not reported

Adverse Events

Classic Interval Group

Serious events: 36 serious events

Other events: 0 other events

Deaths: 1 deaths

Long Interval Group

Serious events: 33 serious events

Other events: 0 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Classic Interval Group n=160 participants at risk İn this arm patients will go under surgery before eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision before 56 days (4-8 weeks): Low anterior resection or abdominoperineal resection	Long Interval Group n=167 participants at risk İn this arm patients will go under surgery after eight weeks, after neoadjuvant chemoradiation therapy. Total mesorectal excision after 56 days (8-12 weeks): Low anterior resection or abdominoperineal resection
Gastrointestinal disorders Anastomotic leakage	2.5% 4/160	2.4% 4/167
Surgical and medical procedures Wound infection	3.8% 6/160	5.4% 9/167
Renal and urinary disorders Urinary leakage	0.62% 1/160	0.00% 0/167
Infections and infestations Pelvic abscess	0.62% 1/160	1.2% 2/167
Surgical and medical procedures Postoperative bleeding	1.2% 2/160	1.2% 2/167
Respiratory, thoracic and mediastinal disorders Atelectasis	1.2% 2/160	0.60% 1/167
Respiratory, thoracic and mediastinal disorders Pneumonia	0.62% 1/160	1.8% 3/167
Renal and urinary disorders Urinary tract infectio	1.9% 3/160	1.2% 2/167
Renal and urinary disorders Prerenal insufficiency	3.1% 5/160	2.4% 4/167
Gastrointestinal disorders Mechanical bowel obstruction	3.1% 5/160	2.4% 4/167
Vascular disorders Deep vein thrombosis, pulmonary embolism	1.2% 2/160	1.2% 2/167
Surgical and medical procedures Other	2.5% 4/160	0.00% 0/167

Other adverse events

Adverse event data not reported

Additional Information

Erhan Akgun,MD, Proffessor

Ege University Hospital

Phone: +902323905050

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place