Optimizing Patient Selection for Surgery Using Pathologic Analysis Following Neoadjuvant Therapy in Locally Advanced Rectal Cancer (OPAL)

Role of Local Endoscopic Excision After Neoadjuvant Therapy in Locally Advanced Rectal Cancer: A Prospective Study

This interventional, non-randomized, prospective trial aims to evaluate the role of endoscopic resection following neoadjuvant treatment in patients with locally advanced rectal cancer.

Phase I focuses on assessing the feasibility, safety and efficacy of endoscopic resection of residual scar or superficial residual neoplastic tissue following neoadjuvant treatment.

Phase II explores the potential of this approach to guide patient selection for total mesorectal excision and to serve as a definitive treatment option for those with limited residual disease.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Rectal Cancer (LARC)
• Intervention / Treatment: Procedure: Total mesorectal excision; Procedure: Endoscopic resection; Behavioral: Short interval restaging

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mariana Figueiredo; Phone Number: +32 23533332; Email: mariana.figueiredo@stpierre-bru.be
• Study Contact Backup: Name: Amélie Deleporte; Phone Number: +32 25354144; Email: amelie.deleporte@stpierre-bru.be

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Recruiting
    • CHU Saint Pierre
    • Contact: Mariana Figueiredo, Medical doctor; Phone Number: +32 25353332; Email: mariana.figueiredo@stpierre-bru.be

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age > 18 years old
• Signed informed consent
• Patients diagnosed with locally advanced rectal cancer showing complete or near-complete clinical response after neoadjuvant therapy without evidence of invasive disease (>T2) or locoregional invasion on magnetic resonance imaging and without any signs of metastatic disease on a computerized tomography scan.
• Patients diagnosed with locally advanced rectal cancer showing incomplete response with presence of superficial residual lesions, without invasive features on endoscopic evaluation, without evidence of invasive disease (>T2) or locoregional invasion on magnetic resonance imaging and without any signs of metastatic disease on a computerized tomography scan.
• Without previous medical history of rectal cancer or rectal surgery

Exclusion Criteria:

• Previous medical history of rectal cancer
• Previous rectal surgery

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: No significant response; Persistant local signs of malignancy	Procedure: Total mesorectal excision; This technique consists of the surgical complete removal of the rectum, together with the surrounding mesorectum lymphovascular fatty tissue (mesorectum).
Experimental: Complete clinical response; Defined as the presence of residual clear scar seen on endoscopic examination, without evidence of invasive disease (>T2) or locoregional invasion on magnetic resonance imaging and without any signs of metastatic disease on a computerized tomography scan.	Procedure: Endoscopic resection; Eligible patients will undergo endoscopic submucosal dissection (ESD) or endoscopic intermuscular dissection (EID) after two to eight weeks of nCRT completion, depending on the used neo-adjuvant regimen. Procedures will be performed using the GIF EZ-1500 endoscope (Olympus America, Center Valley, PA, USA) and an electrosurgical unit (VIO 300 D; Erbe, Germany) to power the electrosurgical knife (1.5-mm DualKnife J, Olympus America). For mucosal incision, Endocut or Drycut mode will be used, while Precise, Swift or Spray Coagulation modes will support submucosal dissection and hemostasis. An initial submucosal lift will be created by Glycéol Gel injection. The ERBE Flushing Pump (Erbe, Germany) will supply further submucosal lift during dissection through foot pedal-controlled, pressurized injections of methylene blue and saline solution delivered via the DualKnife J's ceramic-tipped tubing.
Experimental: Near complete clinical response; Defined as the presence of irregular mucosa or small mucosal nodules or superficial ulceration or persisting erythema of the scar seen on endoscopic examination, without evidence of invasive disease (>T2) or locoregional invasion on magnetic resonance imaging and without any signs of metastatic disease on a computerized tomography scan.	Procedure: Total mesorectal excision; This technique consists of the surgical complete removal of the rectum, together with the surrounding mesorectum lymphovascular fatty tissue (mesorectum).; Procedure: Endoscopic resection; Eligible patients will undergo endoscopic submucosal dissection (ESD) or endoscopic intermuscular dissection (EID) after two to eight weeks of nCRT completion, depending on the used neo-adjuvant regimen. Procedures will be performed using the GIF EZ-1500 endoscope (Olympus America, Center Valley, PA, USA) and an electrosurgical unit (VIO 300 D; Erbe, Germany) to power the electrosurgical knife (1.5-mm DualKnife J, Olympus America). For mucosal incision, Endocut or Drycut mode will be used, while Precise, Swift or Spray Coagulation modes will support submucosal dissection and hemostasis. An initial submucosal lift will be created by Glycéol Gel injection. The ERBE Flushing Pump (Erbe, Germany) will supply further submucosal lift during dissection through foot pedal-controlled, pressurized injections of methylene blue and saline solution delivered via the DualKnife J's ceramic-tipped tubing.; Behavioral: Short interval restaging; Close follow-up and endoscopic re-evaluation four to eight weeks after the initial evaluation*. *Defined as the first endoscopic evaluation after completion of the neoadjuvant treatment
Experimental: Incomplete response with presence of superficial residual tissue; Defined as the presence of superficial residual tissue without features of deep invasion seen on endoscopic examination, without evidence of invasive disease (>T2) or locoregional invasion on magnetic resonance imaging and without any signs of metastatic disease on a computerized tomography scan.	Procedure: Total mesorectal excision; This technique consists of the surgical complete removal of the rectum, together with the surrounding mesorectum lymphovascular fatty tissue (mesorectum).; Procedure: Endoscopic resection; Eligible patients will undergo endoscopic submucosal dissection (ESD) or endoscopic intermuscular dissection (EID) after two to eight weeks of nCRT completion, depending on the used neo-adjuvant regimen. Procedures will be performed using the GIF EZ-1500 endoscope (Olympus America, Center Valley, PA, USA) and an electrosurgical unit (VIO 300 D; Erbe, Germany) to power the electrosurgical knife (1.5-mm DualKnife J, Olympus America). For mucosal incision, Endocut or Drycut mode will be used, while Precise, Swift or Spray Coagulation modes will support submucosal dissection and hemostasis. An initial submucosal lift will be created by Glycéol Gel injection. The ERBE Flushing Pump (Erbe, Germany) will supply further submucosal lift during dissection through foot pedal-controlled, pressurized injections of methylene blue and saline solution delivered via the DualKnife J's ceramic-tipped tubing.; Behavioral: Short interval restaging; Close follow-up and endoscopic re-evaluation four to eight weeks after the initial evaluation*. *Defined as the first endoscopic evaluation after completion of the neoadjuvant treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Endoscopic Resection	Feasibility of the endoscopic resection technique in the context of locally advanced rectal cancer treated with neoadjuvant therapy including radio-chemotherapy. This will be assessed by the curative, en-bloc, and R0 resection rates.	From the endoscopic procedure date to the date of reported pathology results, estimated to a maximum of 15 days
Disease Recurrence	This will be assessed by the rate of local or distant recurrences and the need of salvage surgery within 1, 3 and 5 years following the neoadjuvant treatment and endoscopic resection.	From the endoscopic procedure date until 5 years after the completion of the neoadjuvant therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete endoscopic resection rate	This is defined as the absence of residual visible tissue after endoscopic resection	The day of the endoscopic procedure
En-bloc endoscopic resection rate	This is defined as a single piece endoscopic resection, with clear margins	The day of the endoscopic procedure
Incidence of procedure-related technical complications (Safety of the technique)	This will be defined as any complication occuring during the performance of the endoscopic procedure, such as muscle galling, rectal muscle perforation, minor or major bleeding, anesthesia-related adverse events, endoscopic material defect	The day of the endoscopic procedure
Incidence of early procedure-related adverse events	This will be assessed by evaluating the incidence of procedure-related adverse events (AEs) and serious adverse events (SAEs) within 30 days post-procedure. This includes bleeding rates, perforation rates, infection rates among other complications.	Starting the next day following the endoscopic procedure until 30 days after the procedure
Incidence of late procedure-related adverse events (Long-term safety of the procedure)	This will be assessed by evaluating the incidence of late procedure-related complications within 1, 3 and 5 years after the procedure. This includes delayed haemorrhage, delayed perforation, stenosis, stricture, infection and local pain among other complications	From the endoscopic procedure date until 5 years after the procedure date
Endoscopic tumor characteristics	This will be assessed by the correlation between endoscopic tumor characteristics and the rates of recurrence and salvage surgery. Endoscopic tumor characteristics include the presence of a non-lifting sign, muscle retraction sign, fibrosis, and the description of vessels density (low/moderate/high)	From the endoscopic procedure date until 5 years after the procedure date
Pathologic tumor characteristics	This will be assessed by the correlation between residual tumor characteristics (e.g. resected specimen surface, the presence of residual tumor, tumor differentiation, margin status, lymphovascular invasion (LVI), perineural invasion (PNI), fibrosis degree, tumor budding) and the rates of recurrence and salvage surgery	From the endoscopic procedure date until 5 years after the completion of the neoadjuvant therapy
Pathological response	This will be assessed by the correlation between the degree of pathological response (e.g., complete, partial, or poor response) and the rates of recurrence and salvage surgery	From the endoscopic procedure date until 5 years after the completion of the neoadjuvant therapy
Molecular biomarkers	This will be assessed by evaluating molecular biomarkers such as Next Generation Sequencing (NGS) on the resected specimen, and correlating these findings with the rates of recurrence and salvage surgery	From the pathologic report date until 5 years after the endoscopic procedure date
Survival Outcomes	Overall survival (OS) and disease-free survival (DFS) at 1, 3 and 5 years.	From the endoscopic procedure date until 5 years after the completion of the neoadjuvant therapy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Procedure Duration	The average time taken to perform the endoscopic resection, measured in minutes and reported by the endoscopist	The day of the endoscopic procedure
Length of Hospital Stay	Number of days patients are hospitalized post-procedure	From the endoscopic procedure date to the date of the patient's discharge from the hospital, up to 30 days

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Saint Pierre

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 20, 2024
• First Submitted That Met QC Criteria: December 31, 2024
• First Posted (Actual): January 7, 2025

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 25, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: neoadjuvant; safety; feasibility; endoscopic submucosal dissection; locally advanced rectal cancer; endoscopic resection; endoscopic intermuscular dissection
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Rectal Diseases; Rectal Neoplasms
• Other Study ID Numbers: OPAL202412

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No