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.
The target population consists of adult patients diagnosed with primary gastrointestinal cancers (including but not limited to colorectal cancer, gastric cancer, and gastroesophageal junction cancer) that are histologically confirmed as deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) or harboring polymerase epsilon (POLE) exonuclease domain mutations. All enrolled patients must have received or are scheduled to receive neoadjuvant or conversion immunotherapy prior to definitive local tumor management strategy determination.
Cohort
Other
NOM/OPFS
Other interventionPatients eligible for and consenting to NOM or OPFS. This includes the W\&W strategy for those achieving cCR/near-cCR, and LE or endoscopic resection (ESD/EMR) for those with near-cCR or non-cCR.
Organ Preservation Rate (for OPFS/NOM group)
The percentage of patients in the NOM/OPFS group who successfully maintain their native organ without requiring radical surgical resection or permanent stoma.
Surgical Safety and Postoperative Complications
Incidence and severity of perioperative complications classified by the Clavien-Dindo classification. This compares the safety data among patients undergoing Radical Operation (RO), Local Excision (LE), or endoscopic resection (ESD/EMR).
Pathological Response Distribution (for RO group)
Proportions of patients in the radical operation cohort achieving pathological complete response (ypCR), ypTisN0, ypT1-2N0, and ypT3+ diseases to characterize the pathological efficacy of neoadjuvant immunotherapy.
Local Regrowth / Recurrence Rate
Rate of tumor regrowth in patients undergoing the "Watch \& Wait" strategy, or local recurrence in patients undergoing local/endoscopic excision.
Overall Survival (OS)
Defined as the time from treatment initiation to death from any cause.
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