OBJECTIVE: To define the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC).

BACKGROUND: DAC and iAC share a similar histologic differentiation but the benefit of adjuvant therapy remains unclear.

METHODS: Patients undergoing curative intent surgical resection for DAC and iAC between 2010 and 2021 at 5 high-volume centers were included. Patient baseline, perioperative, and long-term oncological outcomes were evaluated. Statistical testing was performed with SPSS 25 (IBM).

RESULTS: A total of 136 patients with DAC and 171 with iAC were identified. Patients with DAC had more advanced tumors than those with iAC. Median overall survival (OS) in patients with DAC was 101 months versus 155 months for patients with iAC ( P = 0.098). DAC had a higher rate of local (14.1% vs 1.2%, P < 0.001) and systemic recurrence (30.4% vs 3.5%, P < 0.001). Adjuvant therapy failed to improve OS in all patients with DAC and iAC. For DAC, patients with perineural invasion, but not other negative prognostic factors, had improved OS rates with adjuvant therapy (72 vs 44 m, P = 0.044). Patients with iAC with N+ (190 vs 57 m, P = 0.003), T3-T4 (177 vs 59 m, P = 0.050), and perineural invasion (150 vs 59 m, P = 0.019) had improved OS rates with adjuvant therapy.

CONCLUSIONS: While adjuvant therapy fails to improve OS in all patients with DAC and iAC in the current study, it improved OS in patients with DAC with perineural invasion and in patients with iAC with T3-T4 tumors, positive lymph nodes, and perineural invasion.