Intraoperative Systemic Chemotherapy in Stage II-III Appendiceal Adenocarcinoma: A National Cancer Database Analysis

Appendiceal adenocarcinoma is a rare malignancy with a high risk of peritoneal recurrence, especially in locally advanced stages. While intraoperative systemic chemotherapy (ISC) is standard for metastatic disease, its role in non-metastatic Stage II-III patients remains controversial. This study aimed to evaluate the survival benefit of ISC in this population.

We conducted a retrospective cohort study using the National Cancer Database (2006-2022). Patients with clinical Stage II-III (T4, N0-2) appendiceal adenocarcinoma who underwent surgical resection were included. Overall survival (OS) was compared between patients who received ISC and controls using Kaplan-Meier statistics and multivariable Cox proportional hazard models.

A total of 616 patients were identified, 130 (21.1%) of whom received ISC. Patients receiving ISC were more often younger, treated at academic centers, and had mucinous histology. In the unadjusted analysis, ISC was associated with a significantly longer median OS (193.8 vs. 67.7 months, p < 0.001). This survival benefit was significant for Stage II disease (p = 0.007) but not for Stage III (p = 0.43). However, after adjusting for age, grade, clinical stage, and margin status in a multivariable model, ISC was not an independent predictor of improved OS (HR 0.87, 95% CI 0.52-1.47, p = 0.611). In a subgroup analysis of only patients with mucinous and signet-ring cell carcinoma revealed that ISC was independently associated with improved OS (HR: 0.184, 95%CI: 0.044-0.762, p = 0.020).

The findings of this large national cohort do not support the routine use of intraoperative chemotherapy in all patients with non-metastatic appendiceal cancer. However, intraoperative chemotherapy may be associated with an independent survival benefit in patients with mucinous and signet-ring cell carcinomas.