The goal of this real-world study is to learn if maintenance chemotherapy with Tegafur, Gimeracil, and Oteracil Potassium (S-1) can improve disease-free survival (DFS) compared to follow-up observation in patients with resected pancreatic cancer at high risk of recurrence or metastasis after adjuvant therapy. The main questions it aims to answer are:

• Does maintenance therapy with S-1 improve disease-free survival (DFS) compared to follow-up observation after standard treatment for resected high-risk pancreatic cancer?
• Does S-1 maintenance therapy improve overall survival (OS), distant disease-free survival (DDFS), and local recurrence-free survival (LRFS) compared to observation?
• What are the safety and tolerability profiles of S-1 maintenance therapy compared to observation? Researchers will compare two groups: the S-1 maintenance therapy group and the observation-only group, to see if S-1 improves survival outcomes and safety.

Participants will:

• Receive maintenance chemotherapy with S-1 based on body surface area dosing or be assigned to the observation group without drug intervention.
• Undergo imaging evaluations every 12 weeks to monitor for disease recurrence or metastasis.
• Report side effects and any adverse events during the study.

Inclusion Criteria:

1. Histologically confirmed pancreatic cancer (originating from the pancreatic ductal epithelium);
2. Meets one of the following conditions: Pathologically confirmed as moderately differentiated, moderately to poorly differentiated, or poorly differentiated; or pathologic staging as: T3N0M0, T1-3N1-2M0, T4N0-2M0; or one or more surgical margins are R1 resected (R0 resection if no tumor cells are found more than 1mm from the margin, otherwise R1 resection); or involvement of the portal vein and/or superior mesenteric vein resection; or pre-adjuvant chemotherapy CA19-9 > 90 U/mL; or pre-adjuvant chemotherapy ctDNA testing positive;
3. Completed standard treatment: Received radical resection, postoperative adjuvant therapy (including adjuvant chemotherapy based on gemcitabine or fluorouracil), and radiotherapy (if applicable);
4. Eligible for oral medication;
5. Age ≥18 and ≤75, male or female;
6. ECOG performance status: 0 to 2;
7. Normal function of major organs as per the following criteria within 14 days prior to starting treatment:① Neutrophil count ≥ 1.5×10^9/L;② Platelet count ≥ 75×10^9/L;③ Hemoglobin ≥ 9.0 g/dL;④ AST ≤ 2.5×UNL (upper normal limit) (if liver metastasis present, AST ≤ 5×UNL);⑤ ALT ≤ 2.5×UNL (if liver metastasis present, ALT ≤ 5×UNL);⑥ Total bilirubin ≤ 1.5×UNL;⑦ Creatinine clearance (calculated using the Cockcroft-Gault formula) > 60 mL/min or serum creatinine ≤ 1.5×UNL;
8. Women of childbearing potential must have used reliable contraception within 7 days prior to enrollment and have a negative pregnancy test, and must be willing to use appropriate contraception during the study and for 6 months after the last dose of the investigational drug. For men, they must be surgically sterile or agree to use appropriate contraception during the study and for 3 months after treatment;
9. Expected survival time ≥6 months;
10. Voluntary participation in the study, signed informed consent, and demonstrated good compliance and cooperation during follow-up.

Exclusion Criteria:

1. Pancreatic cancer originating from non-pancreatic ductal epithelium, including pancreatic neuroendocrine tumors, pancreatic acinar cell carcinoma, pancreatoblastoma, and solid-pseudopapillary tumor;
2. Incomplete macroscopic resection (R2 resection);
3. Presence of distant metastasis (including malignant ascites and pleural effusion, peritoneal metastasis) or locally recurrent pancreatic cancer;
4. CA19-9 > 180 U/mL within 21 days before enrollment;
5. Severe liver dysfunction (AST/ALT > 3.5 times the upper limit of normal, alkaline phosphatase > 6 times the upper limit of normal), with liver drainage;
6. Known peripheral neuropathy (CTCAE ≥ Grade 2);
7. Participation in another clinical trial of cytotoxic drugs, targeted therapies, immunotherapies, etc., within the past 4 weeks, or received systemic chemotherapy, radiotherapy, or biological therapy within the past 4 weeks;
8. Concurrent or metachronous cancers with disease-free survival ≥ 5 years (excluding pancreatic cancer), except for cancers that have been cured or can be potentially cured with local excision (e.g., esophageal cancer, gastric cancer, colorectal cancer, cervical cancer, non-melanoma skin cancer, bladder cancer);
9. Factors that significantly affect oral drug absorption, such as difficulty swallowing, chronic diarrhea, or gastrointestinal obstruction; uncontrolled Crohn's disease or ulcerative colitis;
10. Clinically symptomatic serous effusions (including pleural effusion, ascites, pericardial effusion) requiring symptomatic treatment;
11. Pregnant or breastfeeding women; patients of childbearing potential unwilling or unable to take effective contraceptive measures;
12. Known allergy to the investigational drug, the class of the investigational drug, or its components;
13. Need for systemic corticosteroid treatment (except for local steroid pre-treatment);
14. History of interstitial lung disease (including interstitial pneumonia, pulmonary fibrosis, etc.) or CT findings of interstitial lung disease;
15. Active local or systemic infection requiring treatment;
16. Heart failure NYHA classification ≥ II or severe heart disease;
17. Known HIV infection or history of acquired immunodeficiency syndrome (AIDS) or active hepatitis B or C;
18. Toxicity not recovered (CTCAE > Grade 1) or previous anticancer surgery not fully recovered;
19. Patients deemed unsuitable for this study by the investigator.