Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal carcinoma with peritoneal and parenchymal metastases.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improve survival in appendiceal carcinoma (AC) with peritoneal dissemination. However, its role in patients with concurrent peritoneal and parenchymal lesions (stage IVc) remains unclear.

METHODS: A multicenter retrospective cohort study of mucinous (MAC) and non-mucinous AC (N-MAC) patients with both intra- and extraperitoneal lesions (liver, lung, or both) was conducted using the National Cancer Database (2004-2019). Overall survival (OS) was evaluated among CRS/HIPEC, surgery alone, and systemic chemotherapy (SCT) cohorts, followed by subgroup analysis performed within each tumor histology and grade.

RESULTS: Out of 42,888 patients, 950 met the inclusion criteria: 186 received CRS/HIPEC, 568 - surgery alone, and 196 - SCT. Median follow-up was 58 months. Median OS after CRS/HIPEC was significantly longer than after surgery alone or SCT in low-grade MAC and N-MAC: not reached (NR) vs 50.0 (95 %CI: 17.2-82.8) vs 26.0 (95 %CI: 12.7-39.3) months (p < 0.01) and NR vs 20.0 (95 %CI: 15.4-24.6) vs 6.0 (95 %CI: 0.0-12.7) months (p < 0.01), respectively. In high-grade AC, median OS did not differ across treatment cohorts. In multivariable analysis, CRS/HIPEC positively impacted OS in low-grade MAC (HR 0.48; 95 %CI: 0.25-0.94; p = 0.03) and N-MAC (HR 0.15; 95 %CI: 0.04-0.58; p < 0.01) but not in high-grade tumors when adjusted by other factors. Younger age, private medical insurance, mucinous pathology, and liver as an extraperitoneal metastatic site were associated with CRS/HIPEC use.

CONCLUSIONS: CRS/HIPEC can provide encouraging outcomes in select low-grade MAC and N-MAC patients with peritoneal and parenchymal metastases. Larger studies are required to assess its efficacy in stage IVc high-grade AC.