Intraoperative Assessment of Distal Resection Margins Using Frozen Section in Mid and Low Rectal Cancer Surgery

This study aims to improve the safety of distal surgical margins in patients with middle and low rectal cancer who receive neoadjuvant radiotherapy. Although magnetic resonance imaging and colonoscopic evaluation after neoadjuvant radiotherapy may suggest complete or near-complete tumor regression, residual tumor cells can still be present in the submucosal and muscular layers of the rectal wall. This may increase the risk of inadequate surgical margins and local recurrence.

In this study, patients with middle and low rectal cancer who are scheduled for surgery after neoadjuvant radiotherapy will be randomized into two groups. In the frozen section group, intraoperative frozen section analysis of the resection specimen will be performed immediately after specimen removal to assess the distal resection margin, and the surgical procedure will be guided according to the frozen section results. In the control group, standard surgical resection will be performed without intraoperative frozen section evaluation.

Pathological findings, distal margin status, operative time, tumor stage, and recurrence during follow-up will be compared between the two groups to evaluate the impact of intraoperative frozen section analysis on surgical margin safety and oncological outcomes.

Study Overview

• Status: Completed
• Conditions: Rectal Cancer
• Intervention / Treatment: Procedure: Intraoperative Frozen Section Assessment; Procedure: Standard Surgery Without Frozen Section

Detailed Description

Middle and low rectal cancers often show a good response to neoadjuvant radiotherapy or chemoradiotherapy. However, despite apparent tumor regression or disappearance on preoperative magnetic resonance imaging and intraoperative colonoscopic evaluation, residual tumor cells may persist within the submucosal or muscular layers of the rectal wall. This residual disease may not be detected by mucosal inspection alone and may lead to inadequate distal resection margins, increasing the risk of local recurrence or the need for more radical surgery.

The primary aim of this study is to evaluate whether intraoperative frozen section analysis of the distal resection margin improves surgical margin safety in patients with middle and low rectal cancer undergoing surgery after neoadjuvant radiotherapy.

This is a prospective, randomized clinical study conducted at Bakırköy Dr. Sadi Konuk Training and Research Hospital. Patients diagnosed with middle or low rectal adenocarcinoma (stage I-III) who have undergone short-course or long-course neoadjuvant radiotherapy and have been discussed in a multidisciplinary oncology council will be included. Following restaging with pelvic magnetic resonance imaging, patients deemed suitable for surgical treatment will be enrolled.

Eligible patients will be randomized into two groups using a sealed-envelope method. All patients will undergo total mesorectal excision according to standard oncologic principles. Immediately before rectal transection, intraoperative colonoscopy will be performed in all patients, and rectal transection will be planned at 2 cm distal to the tumor site identified during colonoscopy using an endoscopic linear stapler.

In the frozen section group, after specimen removal, the resection specimen will be immediately evaluated by an experienced gastrointestinal pathologist using intraoperative frozen section analysis. A distal margin of at least 1 cm will be considered oncologically safe. If the distal margin is found to be positive or closer than 1 cm, further rectal resection will be performed until a safe margin is achieved. If a safe distal margin cannot be obtained despite additional resection, abdominoperineal resection will be performed.

In the control group, after specimen removal, anastomosis will be performed without intraoperative frozen section analysis, and the operation will be completed according to standard surgical practice.

At the end of surgery, all specimens from both groups will undergo routine formalin-fixed pathological examination, including tumor staging and assessment of distal and circumferential resection margins.

Patient demographics, operative time, pathological tumor stage, distal margin status, need for additional resection or abdominoperineal resection, and recurrence during follow-up will be recorded and compared between the two groups.

The results of this study aim to determine whether intraoperative frozen section analysis contributes to safer distal surgical margins and improved oncological decision-making in the surgical treatment of middle and low rectal cancer following neoadjuvant radiotherapy.

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Istanbul
    • Bakırköy, Istanbul, Turkey (Türkiye), 34147
      • Bakırköy Dr. Sadi Konuk Training and Research Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients diagnosed with mid or low rectal cancer (Stage I-III)
• Patients who have received short-course or long-course neoadjuvant radiotherapy
• Patients evaluated and approved for surgery by a multidisciplinary oncology board
• Patients scheduled for total mesorectal excision (TME)
• Age ≥ 18 years
• Patients who provide written informed consent

Exclusion Criteria:

• Stage IV rectal cancer
• Upper rectal tumors
• Patients undergoing emergency surgery
• Patients planned for local excision or palliative surgery
• Patients with distant metastasis
• Patients with a history of previous rectal surgery

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intraoperative Frozen Section Group; Patients undergo total mesorectal excision followed by intraoperative colonoscopy. After specimen removal, distal resection margins are assessed using intraoperative frozen section by an expert pathologist. Additional resection is performed if margins are positive or less than 1 cm. Abdominoperineal resection is performed if a safe margin cannot be achieved.	Procedure: Intraoperative Frozen Section Assessment; Intraoperative pathological evaluation of distal resection margins using frozen section to guide surgical decision-making.
Active Comparator: Control Group; Patients undergo total mesorectal excision followed by intraoperative colonoscopy. Resection is performed 2 cm distal to the tumor using a stapler, and anastomosis is completed without intraoperative frozen section assessment.	Procedure: Standard Surgery Without Frozen Section; Standard surgical resection without intraoperative frozen section assessment of distal margins.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Negative Distal Resection Margin (R0)	Patients who obtained a negative result at the distal resection margin (defined as a tumor-free margin of at least 1 cm) according to intraoperative frozen section examination.	During surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for Additional Resection or Conversion to Abdominoperineal Resection (APR)	The proportion of patients requiring additional distal rectal resection or conversion to abdominoperineal resection due to positive or insufficient distal resection margins.	During surgery
Local Recurrence Rate	The incidence of local tumor recurrence during postoperative follow-up, confirmed by imaging, endoscopy, or pathological evaluation.	During postoperative follow-up (12- 24 months)
Operative Time	Total duration of the surgical procedure measured from skin incision to completion of wound closure.	During surgery

Collaborators and Investigators

• Sponsor: Bakirkoy Dr. Sadi Konuk Research and Training Hospital
• Investigators: Principal Investigator: Nurettin Sahin, MD, Bakırköy Dr. Sadi Konuk Training and Research Hospital

Publications and helpful links

General Publications

• Gomes RM, Bhandare M, Desouza A, Bal M, Saklani AP. Role of intraoperative frozen section for assessing distal resection margin after anterior resection. Int J Colorectal Dis. 2015 Aug;30(8):1081-9. doi: 10.1007/s00384-015-2244-4. Epub 2015 May 16.
• Khoury W, Abboud W, Hershkovitz D, Duek SD. Frozen section examination may facilitate reconstructive surgery for mid and low rectal cancer. J Surg Oncol. 2014 Dec;110(8):997-1001. doi: 10.1002/jso.23758. Epub 2014 Sep 2.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Actual): January 1, 2025
• Study Completion (Actual): January 1, 2026

Study Registration Dates

• First Submitted: January 25, 2026
• First Submitted That Met QC Criteria: February 2, 2026
• First Posted (Actual): February 10, 2026

Study Record Updates

• Last Update Posted (Actual): February 11, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: frozen section; Low rectal cancer; Distal resection margin; Mid rectal cancer
• 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; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytological Techniques; Histological Techniques; Histocytological Preparation Techniques; Cryoultramicrotomy; Microtomy; Frozen Sections
• Other Study ID Numbers: IOFS-DM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared, as the study is a single-center trial and data sharing was not included in the original ethics committee approval. De-identified aggregate data may be available upon reasonable request to the corresponding investigator

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No