Safety and Efficacy of Nonoperative Management (NOM) and Organ Preservation First Strategy (OPFS) Versus Radical Operation (RO) for dMMR/MSI-H or POLE-Mutated Gastrointestinal Cancers: A Single-Center, Bidirectional Registry Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 22
Study Overview
Brief Summary
Purpose:
The purpose of this study is to evaluate the safety and efficacy of Non-Operative Management (NOM) and Organ Preservation First Strategy (OPFS) compared with Radical Operation (RO) in patients with deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) or POLE-mutated gastrointestinal cancers.
Background & Design:
With the remarkable efficacy of neoadjuvant immunotherapy in dMMR/MSI-H or POLE-mutated gastrointestinal tumors, organ preservation has become a promising alternative to highly invasive surgeries. The NOR-MP trial is a single-center, bidirectional registry study consisting of two parts: a retrospective cohort study and a prospective observational registry.
Intervention Group (NOM/OPFS): Patients who achieve a clinical complete response (cCR) or near-cCR after neoadjuvant immunotherapy will undergo a "Watch & Wait" (W&W) strategy. Patients with near-cCR or non-cCR who are eligible for organ preservation will undergo local excision (LE) or endoscopic resection (including ESD or EMR).
Comparison Group (Radical Operation): Patients who undergo standard radical surgical resection after neoadjuvant immunotherapy.
The study aims to determine whether an organ-preserving approach can achieve comparable oncological outcomes and safety profiles while significantly improving patients' quality of life compared to radical surgery.
Detailed Description
The NOR-MP trial is a single-center, bidirectional registry study designed to compare the clinical outcomes of Organ Preservation First Strategy (OPFS) / Non-Operative Management (NOM) against standard Radical Operation (RO) for patients diagnosed with dMMR/MSI-H or POLE-mutated gastrointestinal cancers. The study is divided into two sequential parts based on the nature of data collection:
Part 1: Retrospective Cohort Study
This part retrospectively reviews the medical records of eligible patients with dMMR/MSI-H or POLE-mutated gastrointestinal cancers who previously completed neoadjuvant immunotherapy. Patients are allocated into two historical cohorts:
Experimental Cohort (NOM/OPFS): Patients who achieved cCR/near-cCR after neoadjuvant immunotherapy and entered the "Watch & Wait" (W&W) program, as well as those with near-cCR or non-cCR who underwent local excision (LE) or endoscopic resection (including Endoscopic Submucosal Dissection [ESD] or Endoscopic Mucosal Resection [EMR]).
Control Cohort (RO): Patients who underwent radical surgical operation after neoadjuvant immunotherapy. Pathological outcomes (including the proportions of ypCR, ypTisN0, and ypT1-2N0) and surgical safety data will be collected and analyzed.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Other
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically confirmed primary gastrointestinal adenocarcinoma or squamous cell carcinoma (e.g., colorectal cancer, gastric cancer, gastroesophageal junction cancer).
- •Confirmed as deficient mismatch repair (dMMR) by immunohistochemistry (IHC), high microsatellite instability (MSI-H) by polymerase chain reaction (PCR) or next-generation sequencing (NGS), or harboring POLE exonuclease domain mutations.
- •Received neoadjuvant/conversion immunotherapy (immune checkpoint inhibitors, either monotherapy or combination therapy) prior to treatment response evaluation.
- •For the Retrospective Cohort (Part 1): Patients treated between [Start Month/Year] and [End Month/Year] who completed evaluation and subsequent strategy (NOM/OPFS or RO).
- •For the Prospective Cohort (Part 2): Newly diagnosed patients who consent to long-term follow-up and multi-disciplinary team (MDT) assessment for organ preservation or radical surgery.
- •Age ≥ 18 years at the time of diagnosis.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion Criteria
- •Concurrently diagnosed with other active malignant tumors within the past 5 years.
- •Patients with proficient mismatch repair (pMMR) / microsatellite stable (MSS) tumors, or wild-type POLE status.
- •Evidence of untreatable distant metastasis or systemic disease that precludes local tumor management (NOM/OPFS or radical operation).
- •Inability to undergo regular endoscopic, radiological (MRI/CT), or clinical follow-up due to compliance or geographic reasons.
- •Refusal to sign the informed consent form (applicable to the prospective cohort).
Investigators
Xiaokang Lei
Dr.
Peking University Cancer Hospital & Institute