Appendiceal cancer: Historical trends in histological composition and cause-specific mortality based on SEER database analysis.

Abstract

e16485 Background: Appendiceal cancers are rare malignancies characterized by marked histologic heterogeneity and diverse clinical behavior. Although the incidence has increased over recent decades, long-term population data describing mortality patterns and competing causes of death remain limited. We examined trends in histologic distribution and all-cause mortality among patients with appendiceal cancer using the Surveillance, Epidemiology, and End Results (SEER) Research Plus database. Methods: We conducted a retrospective cohort study of patients diagnosed with primary appendiceal malignancies between 2000 and 2022 using the SEER Plus database. Demographic characteristics, tumor features, stage, and treatment variables were extracted. Histologic subtypes were defined using International Classification of Diseases for Oncology, Third Edition (ICD-O-3) morphology codes and categorized into the following types: colonic type adenocarcinoma, mucinous adenocarcinoma, malignant carcinoid tumor, neuroendocrine neoplasms, and signet ring cell carcinoma. Mortality causes were evaluated using cumulative incidence functions and Fine-Gray subdistribution hazard models, treating non-appendiceal cancer deaths as competing risks. Results: A total of 16,739 patients met the inclusion criteria. Malignant carcinoid tumors were the most common histology (45.6%), followed by mucinous adenocarcinoma (27.6%) and colonic-type adenocarcinoma (18.5%). Linear regression analysis demonstrated significant temporal increases in proportion for malignant carcinoid tumors (R² = 0.824, p < 0.001), with malignant carcinoid tumors surpassing other subtypes to become the predominant histology after 2015. There was a decrease in mucinous adenocarcinoma (R² = 0.824, p < 0.001) and colonic-type adenocarcinoma (R2 = 0.898, p < 0.001) histologies. Appendiceal cancer-specific death was the leading cause of mortality overall. Non-cancer causes, particularly cardiovascular disease, represented an important competing risk during long-term follow-up. In multivariable Fine-Gray models, colonic-type adenocarcinoma and signet ring cell carcinoma were associated with significantly higher appendiceal cancer-specific mortality compared with malignant carcinoid tumors (p < 0.001). Surgical resection was consistently associated with reduced cancer mortality, while advanced age and those who received chemotherapy were associated with higher cancer-specific mortality. Conclusions: Appendiceal cancer exhibits evolving histologic patterns with substantial heterogeneity in cancer-specific mortality. While appendiceal cancer remains the predominant cause of death, cardiovascular disease represents an important competing risk, particularly among patients with indolent histologies and longer survival.