Negative Impact of Systemic Therapy on Survival in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Low-Grade Metastatic Appendiceal Adenocarcinoma.

BACKGROUND: Despite studies demonstrating that patients with peritoneal metastases from low-grade appendiceal adenocarcinoma (AA) do not respond well to systemic chemotherapy (SC), patients frequently undergo combination of SC with cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) regardless of grade.

METHODS: A nationwide retrospective analysis using the National Cancer Database evaluated patients with AA with peritoneal metastasis from 2016 to 2021. Cox proportional hazards model was used to evaluate the impact of SC in addition to CRS/HIPEC on overall survival (OS) stratified by tumor grade.

RESULTS: A total of 1,449 patients were included: 481 low-grade, 428 intermediate-grade, and 540 high-grade tumors. Clinical variables, such as age, sex, and comorbidity index, were similar across tumor grades. Cytoreductive surgery/hyperthermic intraperitoneal chemotherapy without SC was utilized in 65.73% of low-grade cases compared with 41.01% in intermediate-grade and 11.11% in high-grade cases. Systemic chemotherapy was utilized alone in 17.74% and with CRS/HIPEC in 16.53% of low-grade cases. In adjusted survival analysis, addition of SC to CRS/HIPEC was associated with worse OS for patients with low-grade AA (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.18-6.50) but not for intermediate (HR 1.65, 95% CI 0.82-3.35) and high-grade tumors (HR 1.18, 95% CI 0.67-2.45). The addition of time to definitive surgery variable nullified the negative impact of adding SC to CRS/HIPEC in low-grade AA (HR 1.76, 95% CI 0.68-4.53).

CONCLUSIONS: Negative OS impact of SC may be mediated by delays in effective surgical/intraoperative therapy. If CRS/HIPEC is planned for patients with metastatic low-grade AA, avoiding SC may facilitate earlier surgical intervention and improve survival.