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.
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).
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.