Non-Operative Management and Following Immunotherapy for Colorectal Cancer and Other GI Cancers

Non-Operative Management and Following Immunotherapy for Colorectal Cancer and Other GI Cancers (NOMIC Trial)

This is a single-center, bidirectional (retrospective and prospective) registry study aimed at evaluating the safety and efficacy of Non-Operative Management (NOM) and Organ-Preserving Functional Surgery (OPFS) in patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) or POLE-mutated gastrointestinal (GI) cancers who received neoadjuvant immunotherapy.Patients achieving a clinical complete response (cCR) or near-cCR may undergo a "Watch & Wait" (W&W) strategy, while those with near-cCR or non-cCR ($\le ymrT2N0$) may undergo local excision (LE) or endoscopic resection (ESD/EMR). Patients undergoing radical operation (RO) will serve as the control cohort to compare oncological outcomes and safety data.

Inclusion Criteria:

1. Retrospective Cohort Inclusion Criteria

   • Pathologically confirmed gastrointestinal malignancy determined as MSI-H/dMMR or POLE mutation, and initially resectable.
   • Completed prior immunotherapy.
   • No evidence of distant metastasis.
   • Managed with W&W, LE, endoscopic surgery, or radical operation after treatment.

2. Prospective Cohort Inclusion Criteria

   • Pathologically confirmed gastrointestinal malignancy determined as MSI-H/dMMR or POLE mutation, and initially resectable.
   • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
   • Immunotherapy status: naive, currently receiving, or completed treatment, and evaluated by the PKUCH-NOMIC research group as cCR/near-cCR or Non-cCR (≤ ymrT2N0).
   • No evidence of distant metastasis.
   • Absence of emergencies requiring immediate surgery (e.g., hemorrhage, perforation, obstruction).

Exclusion Criteria:

• Recurrent gastrointestinal tumors.Initial presence of unresectable distant metastases.
• Serum creatinine > 1.5 times upper limit of normal (ULN).
• History of pelvic radiation therapy.Inability to tolerate MRI examinations.
• History of other malignancies within the past 5 years with a survival rate significantly lower than the historical rectal cancer survival data of this center (except adequately treated basal cell carcinoma, cutaneous squamous cell carcinoma, small renal cell carcinoma, breast cancer, and papillary thyroid carcinoma).
• Arterial thromboembolic events within the past 6 months (e.g., angina, myocardial infarction, transient ischemic attack [TIA], cerebral vascular accident [CVA]).
• Prior receipt of other types of investigational anti-tumor therapies.
• Pregnant or lactating women.
• Concomitant diseases or mental health conditions that may interfere with study participation.