Response-adapted total neoadjuvant therapy guided by induction chemotherapy to enable a watch-and-wait approach for low rectal cancer

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 project will see if people with mid-to-low rectal cancer who respond well to induction chemotherapy can avoid immediate surgery and be safely managed with a watch-and-wait approach after completing total neoadjuvant therapy.

Quick facts

• Study type: Observational
• Enrollment: 60 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: West China Hospital (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT07260526 on ClinicalTrials.gov

What this trial studies

The study combines retrospective and prospective cohorts of patients with mid-to-low rectal adenocarcinoma treated at West China Hospital who complete induction chemotherapy and total neoadjuvant therapy (TNT). Eligible patients meet early- to intermediate-risk criteria (cT1-3abN0-1M0, pMMR/MSS, tumor ≤5 cm from the anal verge, ≤2/3 circumference) and must show a treatment response after at least two cycles of XELOX (≥30% tumor length reduction). Patients are followed with serial imaging and clinical exams to record organ preservation (watch-and-wait) rates, patterns of recurrence, and the need for salvage surgery. Functional recovery and quality-of-life outcomes are compared to historical outcomes after radical surgery to preliminarily evaluate feasibility of non-surgical management.

Who should consider this trial

Good fit: Ideal candidates are adults (18–80) with mid-to-low rectal adenocarcinoma of early-to-intermediate stage (cT1-3abN0-1M0), pMMR/MSS status, tumor ≤5 cm from the anal verge and ≤2/3 circumference, who show at least a 30% tumor length reduction after induction XELOX and complete total neoadjuvant therapy.

Not a fit: Patients who do not respond to induction chemotherapy, have higher-risk features (e.g., MRF involvement, positive lateral nodes, larger tumors), metastatic disease, or who cannot complete TNT are unlikely to benefit from a watch-and-wait approach.

Why it matters

Potential benefit: If successful, this approach could allow some patients to keep their rectum and have better bowel, urinary, and sexual function without compromising long-term cancer control.

How similar studies have performed: Multiple prior observational studies have reported that patients who achieve a clinical complete response after TNT can have disease-free and overall survival rates similar to those after radical surgery, though randomized data remain limited.

Eligibility criteria

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.

Where this trial is running

Chengdu, Sichuan

• West China hospital, Sichuan University — Chengdu, Sichuan, China (RECRUITING)

Study contacts

• Study coordinator: Ziqiang Wang, M.D.

Conditions: Rectal Cancer, rectal cancer, total neoadjuvant therapy, watch-and-wait strategy