NCT07337811

Selective Total Mesorectal Excision Based on Intra-Operative Frozen Section From Local Excision in Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy

Selective Total Mesorectal Excision Based on Intra-Operative Frozen Section From Local Excision in Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy: A Prospective, Single-arm, Phase II Superiority Trial

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This study is a prospective, single-arm, phase II superiority trial to determine whether a selective organ-preserving strategy based on immediate intra-operative frozen-section results can achieve favorable 2-year local control while lowering morbidity in patients with low rectal cancer (tumor ≤5 cm from the anus) who have a near clinical complete response (near-cCR) or partial response (residual tumor \<2 cm) after radiation therapy. Population: Adults with primary rectal adenocarcinoma located ≤5 cm from the anal verge who, after neoadjuvant radiotherapy, are judged to have near-cCR or partial response (residual tumor \<2 cm). Intervention: All participants undergo local excision under general anesthesia. The specimen is sent for intra-operative frozen section. ypT0-1 on frozen section → procedure concluded; patient enters watch-and-wait. ypT2-3 or R1 on frozen section → immediate completion total mesorectal excision (TME). Frozen-section ypT1-2 but final paraffin section up-staged to ypT2-3 or R1 → elective TME within 8 weeks. Primary Endpoint: a composite outcome of 2-year local recurrence rate, surgical complications (≤30 days), and long-term functional impairment (anorectal, urogenital, and quality-of-life scales). Secondary Endpoints: Agreement between intra-operative frozen-section pathology and final paraffin-section pathology, 3-year disease-free survival (DFS), 3-year overall survival (OS), surgery-sparing rate, post-operative recovery metrics, Quality-of-life scores. Estimated Enrollment: 27 participants.

Detailed description

Rectal cancer is a major global health burden with high morbidity and mortality. Its prognosis is generally worse than that of colon cancer, largely because of a higher risk of local recurrence. In 1982, Bill Heald introduced total mesorectal excision (TME), which has since proven to markedly reduce local recurrence. Peri-operative radiotherapy and chemotherapy further improve outcomes; pre-operative chemoradiotherapy (CRT) is superior to post-operative CRT, cutting local relapse by \~50%. Current National Comprehensive Cancer Network (NCCN) guidelines therefore recommend "pre-operative concurrent CRT followed by radical surgery" for locally advanced (stage II/III) rectal cancer. More recently, total neoadjuvant therapy (TNT) has refined this strategy, increasing pathologic complete response (pCR) rates to 20-40 %, and up to 60 % when combined with immunotherapy. After neoadjuvant treatment, approximately 20 % of tumors achieve complete regression with pCR. If pre-operative assessment shows a clinical complete response (cCR), these patients may be offered an organ-preserving "watch-and-wait" approach instead of immediate TME, preserving sphincter function and quality of life. Since Habr-Gama's first report, multiple studies have confirmed the safety of this strategy: among patients managed by watch-and-wait, 15-20 % develop regrowth, 95 % of which are local and salvageable; 3-year distant-metastasis rates are only 8 % and 5-year cancer-specific survival is 94 %. Consequently, watch-and-wait is now standard for patients with cCR after CRT. However, only 10-20 % of patients who ultimately achieve pCR are judged cCR pre-operatively. Imaging or endoscopic uncertainties (e.g., minimal ulceration) often lead to classification as partial response (PR) or near-cCR, depriving these patients of organ preservation. Traditionally, such patients proceed directly to TME. An emerging alternative is "local excision ± salvage TME": trans-anal full-thickness excision is performed first; if final pathology shows ypT0-1, no further surgery is required, whereas ypT2-3 or R1 margins trigger elective salvage TME. This risk-stratified approach aims to preserve organs in good responders while ensuring oncologic safety in poor responders. Yet the GRECCAR-2 trial raised concerns: prior local excision may complicate subsequent TME, compromise sphincter preservation, and increase peri-operative morbidity (bleeding, infection, anorectal dysfunction) and long-term functional impairment. For patients with excellent tumor regression after CRT, these risks pose a dilemma. To address this challenge, we propose the present clinical study, evaluating whether intra-operative frozen-section guidance during local excision can maintain diagnostic accuracy and oncologic safety while reducing the surgical complications and long-term functional sequelae associated with deferred TME. This study is a prospective, single-arm, phase II superiority trial to determine whether a selective organ-preserving strategy based on immediate intra-operative frozen-section results can achieve favorable 2-year local control while lowering morbidity in patients with low rectal cancer (tumor ≤5 cm from the anus) who have a near clinical complete response (near-cCR) or partial response (residual tumor \<2 cm) after radiation therapy. Population: Adults with primary rectal adenocarcinoma located ≤5 cm from the anal verge who, after neoadjuvant radiotherapy, are judged to have near-cCR or partial response (residual tumor \<2 cm). Intervention: All participants undergo local excision under general anesthesia. The specimen is sent for intra-operative frozen section. ypT0-1 on frozen section → procedure concluded; patient enters watch-and-wait. ypT2-3 or R1 on frozen section → immediate completion total mesorectal excision (TME). Frozen-section ypT1-2 but final paraffin section up-staged to ypT2-3 or R1 → elective TME within 8 weeks. Primary Endpoint: a composite outcome of 2-year local recurrence rate, surgical complications (≤30 days), and long-term functional impairment (anorectal, urogenital, and quality-of-life scales). Secondary Endpoints: Agreement between intra-operative frozen-section pathology and final paraffin-section pathology, 3-year disease-free survival (DFS), 3-year overall survival (OS), surgery-sparing rate, post-operative recovery metrics, Quality-of-life scores. Estimated Enrollment: 27 participants.

Conditions

• Rectal Cancer Patients

Interventions

Type	Name	Description
PROCEDURE	Selective Total Mesorectal Excision Based on Intra-Operative Frozen Section From Local Excision	All participants undergo trans-anal full-thickness local excision under general anesthesia. The specimen is sent for intra-operative frozen-section pathology. ypT0-1 on frozen section → procedure concluded; patient enters watch-and-wait. ypT2-3 or R1 on frozen section → immediate completion total mesorectal excision (TME). Frozen-section ypT1-2 but final paraffin section up-staged to ypT2-3 or R1 → elective TME within 8 weeks.

Timeline

• Start date: 2025-08-01
• Primary completion: 2028-07-31
• Completion: 2028-07-31
• First posted: 2026-01-13
• Last updated: 2026-01-13

Locations

1 site across 1 country: China