Adjuvant Chemotherapy with S1 After Radical Cholecystectomy for Gallbladder Cancer
S1 (tegafur/gimeracil/oteracil) for 6 months is an appropriate adjuvant chemotherapy approach for gallbladder cancer with positive lymph nodes after radical cholecystectomy with negative margins. This recommendation is supported by clinical guidelines and evidence showing survival benefit in patients with high-risk features such as lymph node positivity.
Evidence Supporting S1 Adjuvant Therapy
- A 6-month course of oral fluoropyrimidine (capecitabine or S1) is strongly recommended following potentially curative resection of biliary tract cancers according to recent guidelines 1
- The ASCOT trial in Japan demonstrated that adjuvant therapy with four 6-weekly cycles of S1 (tegafur-gimeracil-oteracil) led to significantly longer survival than surgery alone (HR 0.694, P = 0.008) 1
- For patients with high-risk features such as node-positive disease, adjuvant fluoropyrimidine-based chemotherapy is recommended to reduce recurrence risk 2
Risk Stratification and Treatment Rationale
- Patients with positive lymph nodes (as in your case) are at high risk for recurrence and show particularly pronounced benefit from adjuvant therapy 2
- The presence of 4 positive lymph nodes represents a significant risk factor for recurrence, making adjuvant therapy strongly indicated 2
- Negative liver and cystic duct margins (R0 resection) are favorable prognostic factors, but lymph node positivity still warrants adjuvant treatment 1
Treatment Options and Rationale for S1
- S1 has been shown to be effective in biliary tract cancers and has demonstrated feasibility as adjuvant therapy with a high completion rate of 81.8% in clinical studies 3
- Fluoropyrimidine-based regimens (including S1) are the standard of care for adjuvant therapy in biliary tract cancers based on positive clinical trials 1
- The 6-month duration aligns with established protocols from major clinical trials and guidelines 1
Expected Outcomes
- Adjuvant chemotherapy significantly improves survival in node-positive gallbladder cancer patients 4
- In patients with resected biliary tract cancer receiving S1 adjuvant therapy, 3-year relapse-free survival rate was 39.4% and 3-year overall survival rate was 54.5% 3
- Without adjuvant therapy, patients with node-positive disease have significantly worse outcomes (median survival of 5 months vs 16 months with treatment) 2
Potential Side Effects and Management
- The most common grade 3/4 adverse event with S1 is neutropenia (18%) 3
- Grade 2 nausea or diarrhea may occur in approximately 12% of patients 3
- S1 has shown favorable tolerability compared to other regimens, with many patients able to complete the full course of therapy 3
Conclusion
The recommendation of S1 for 6 months as adjuvant chemotherapy is appropriate for this patient with gallbladder cancer who has undergone radical cholecystectomy with negative margins but positive lymph nodes. This approach is supported by clinical guidelines and evidence showing survival benefit in high-risk patients, particularly those with lymph node involvement.