Research on Effective Strategies After Immunotherapy for Mismatch Repair-deficient Early-stage GI Tumors

Inclusion Criteria: Part A and Part B: * Consent and Capacity: * Participant is 18 years of age or older. * Participant is legally competent and able to provide informed consent. * Participant has provided the appropriate written consent * Diagnosis: Histologically confirmed gastro-oesophageal, colon or rectum cancer, showing mismatch repair-deficiency (MMRd) by immunohistochemistry (loss of immunoreactivity for at least one of the following proteins: MLH1, PMS2, MSH2 and/or MSH6). * Clinical Stage: Non-metastatic, locally advanced disease, defined as: * cT2-T4, cN0-2, cM0 for gastro-oesophageal or rectum cancer * cT4 and/or cN+, cM0 for colon cancer * Therapy with immune checkpoint inhibitor (ICI) as primary treatment, either: * Combination ICI therapy (e.g., anti-PD-1 plus anti-CTLA-4 such as nivolumab + ipilimumab) or * Single-agent ICI therapy (e.g., pembrolizumab, atezolizumab, or other anti- PD(L)1 agents) Part B only: * Patient consents to participate in surveillance study * Complete or near complete response (\*) to primary ICI treatment, as determined by local multidisciplinary team (MDT) assessment, based on restaging 8 weeks after termination of the ICI treatment: * Radiological imaging (CT/MRI/PET-CT), * Endoscopic findings, and * Clinical parameters (e.g., normalization of tumor markers, absence of symptoms \*\*) * Note: in case of near complete response up to a total of 12 months of ICI is allowed following multidisciplinary team (MDT) discussion. After diagnosis of a near-complete response, tumor reassessments should be performed every 3 months up to a total treatment period of 12 months. If a complete tumor response is observed within the 12-month period, it should be recorded as the best overall response. * Note: Assessment of complete or near complete response does not incorporate ctDNA test results Exclusion Criteria: * Recurrent Disease: Known history of previously treated gastrointestinal cancer with recurrence at time of inclusion. * Metastatic Disease: Evidence of distant metastases (M1) at any point prior to or during ICI therapy. * Other Malignancies: Active second malignancy (excluding non-melanoma skiN cancer or in-situ cervical carcinoma) that may interfere with study outcomes or surveillance. Part B only: * Inadequate response to ICI: Patients with progressive disease, stable disease, or partial response deemed unsuitable for non-operative management. * Prior Treatment: Any prior systemic therapy, radiotherapy or surgery for the current colon cancer diagnosis before ICI treatment (except biopsy) * Medical or Psychiatric Conditions: Significant comorbid conditions or psychiatric illness that, in the opinion of the investigator, would impair the patient's ability to comply with protocol requirements, including surveillance. * Logistical Barriers: Social, geographic, or organizational factors (e.g., lack of access to regular follow-up care, inability to attend surveillance visits) that would prevent adherence to the active surveillance protocol.