Is Adjuvant Chemotherapy Necessary for Stage IIB/IIC Appendiceal Adenocarcinoma?

Abstract

Introduction

Appendiceal adenocarcinoma is a rare and heterogeneous malignancy with management strategies historically mirroring those of colorectal cancer. The role of adjuvant chemotherapy (AC) in stage II disease remains poorly studied, particularly in stage IIB/IIC. We evaluated the impact of AC on overall survival (OS) in stage IIB/IIC appendiceal adenocarcinoma using the National Cancer Database (NCDB).

Methods

The NCDB was queried to identify adults diagnosed with stage IIB/IIC appendiceal adenocarcinoma from 2010 to 2021. Patients with carcinoid, goblet cell, or neuroendocrine histologies were excluded. Patients were stratified into surgery alone (S) or surgery plus adjuvant chemotherapy (S+). Kaplan-Meier and log-rank tests estimated survival distributions, and multivariable Cox proportional hazards regression with Firth’s correction assessed independent predictors of OS.

Results

2082 patients met inclusion criteria. Adequate lymph node evaluation (≥12 nodes) was independently associated with improved survival (aHR: 0.62, P < .0001). Adjuvant chemotherapy conferred a significant survival benefit, with a 26% reduction in risk of death (aHR: 0.74, 95% CI: 0.62-0.89, P = .0016). Five-year OS was 78.9% for S+ vs 68.7% for S (P < .001). Patients receiving both AC and adequate nodal harvest demonstrated the greatest survival benefit. Non-mucinous histology was associated with superior outcomes compared to mucinous disease (aHR: 0.62, P < .0001).

Conclusion

Adjuvant chemotherapy is independently associated with improved survival in patients with stage IIB/IIC appendiceal adenocarcinoma, particularly when combined with adequate lymph node evaluation. These findings challenge current treatment paradigms that extrapolate from colorectal cancer and support consideration of AC as standard therapy in this high-risk patient subset.