Response-adapted Total Neoadjuvant Therapy Guided by Induction Chemotherapy in Early- and Intermediate-risk Low Rectal Cancer for Implementation of a Watch-and-wait Strategy

This study investigates the feasibility of an organ-preserving "watch-and-wait" strategy in patients with mid-to-low rectal cancer who achieve a good response after total neoadjuvant therapy (TNT). By retrospectively and prospectively analyzing patients who complete TNT following effective induction chemotherapy, the study aims to assess organ preservation rates and evaluate whether non-surgical management can provide comparable oncologic outcomes to radical surgery while improving functional recovery and quality of life.

Study Overview

• Status: Recruiting
• Conditions: Rectal Cancer

Detailed Description

With the evolution of rectal cancer treatment concepts, achieving optimal oncologic outcomes while preserving organ function and improving patients' quality of life has become a major goal in the management of low rectal cancer. Multiple studies have reported that for patients who achieve a clinical complete response (cCR) after total neoadjuvant therapy (TNT), a watch-and-wait (organ preservation) strategy-with close follow-up and salvage surgery when necessary-yields 5-year disease-free survival (DFS) and overall survival (OS) rates comparable to those of patients who undergo radical surgery and achieve a pathological complete response (pCR). Moreover, compared with total mesorectal excision (TME), patients managed with a watch-and-wait approach demonstrate significantly better physical, cognitive, role, and social-emotional functioning, along with lower incidences of bowel, sexual, and urinary dysfunction.

This study aims to retrospectively and prospectively include patients with mid-to-low rectal cancer who respond well to induction chemotherapy and subsequently complete TNT, in order to observe the organ preservation rate after TNT and to preliminarily evaluate the feasibility of this treatment approach within a watch-and-wait strategy.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Ziqiang Wang, M.D.; Phone Number: +86 18980602028; Email: wangziqiang@scu.edu.cn

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital, Sichuan University
      • Contact: Ziqiang Wang, M.D.; Phone Number: +86 189 8060 2028; Email: wangziqiang@scu.edu.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with mid-to-low rectal cancer who respond well to induction chemotherapy and subsequently complete total neoadjuvant therapy in order to observe the organ preservation rate after total neoadjuvant therapy.

Description

Inclusion Criteria:

• Age: 18-80 years; no restriction on sex.
• Histologically confirmed rectal adenocarcinoma with immunohistochemistry and/or genetic testing showing pMMR/MSS status.

• Tumor characteristics assessed by chest-abdominal CT, rectal ultrasound, and MRI meeting all of the following criteria:

  1. The lower edge of the tumor is ≤5 cm from the anal verge as measured by digital rectal examination or MRI;
  2. Clinical stage cT1-3abN0-1M0 (for cT1N0, patients suitable for endoscopic resection are excluded);
  3. MRF (-) (>1 mm), EMVI (±);
  4. Negative lateral lymph nodes and <7 mm in size;
  5. Maximum tumor length ≤5 cm;
  6. Tumor circumference involvement ≤2/3.
• After receiving at least two cycles of induction chemotherapy with the XELOX regimen, MRI assessment shows treatment response (tumor length reduced by ≥30% compared with baseline).
• Completion of total neoadjuvant therapy (TNT), including long-course chemoradiotherapy and consolidation chemotherapy (radiotherapy: 25-28 fractions; chemotherapy: 6-8 cycles).
• (For the prospective cohort) Provision of written informed consent for participation in this observational study.

Exclusion Criteria:

• Patients with a history of, or concurrent, other malignant tumors (except for cured basal cell carcinoma of the skin or carcinoma in situ of the cervix);
• Patients with severely incomplete clinical data that preclude effective evaluation;
• (For the prospective cohort) Patients who refuse to provide written informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ITNT group; Patients who achieve a good response after total neoadjuvant therapy and receive organ preservation strategy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year organ preservation rate	defined as the proportion of the following two groups among the total study population：① Patients evaluated as having a clinical complete response (cCR) or near cCR at 8 weeks after radiotherapy who choose a watch-and-wait strategy and maintain cCR for 1 year; ② Patients evaluated as having a cCR or near cCR at 8 weeks after radiotherapy who ultimately undergo local excision and remain recurrence-free for 1 year without requiring salvage surgery.	1 year after completion of neoadjuvant radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year metastasis-free survival	time from the start of neoadjuvant chemotherapy to the occurrence of distant metastasis	1 year after total neoadjuvant therapy
1-year overall survival	time from the start of neoadjuvant chemotherapy to death from any cause.	1 year after total neoadjuvant therapy

Collaborators and Investigators

• Sponsor: West China Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 30, 2026

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: December 2, 2025
• First Posted (Estimated): December 3, 2025

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: rectal cancer; total neoadjuvant therapy; watch-and-wait strategy
• 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: WCH20250924

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Researchers are encouraged to apply for the full study protocol, study data, and analytic code upon reasonable request by contacting the primary investigator (Ziqiang Wang).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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