Cancer of the appendix – still rare but increasing in incidence

Review by Prof. Eamonn Quigley (USA)

Study Summary 

Cancer of the appendix is rare, and while the overall outlook is good for incidentally discovered neuroendocrine tumors and low-grade appendiceal mucinous neoplasms (LAMN), survival for advanced-stage colonic-type and mucinous adenocarcinomas is poor. Stimulated by the suggestion that there has been an increase in incidence of appendiceal adenocarcinoma in recent decades, this study used data from the National Institutes of Health and the National Cancer Institute’s surveillance, epidemiology, and end result (SEER) program to examine trends in appendiceal adenocarcinoma incidence. 4858 adults with pathologically confirmed appendiceal adenocarcinoma were included, and incidence rates in birth cohorts from every decade from 1900 to 1990 calculated. Three histological types, mucinous, non-mucinous, and goblet cell, were differentiated. Compared with the 1945 birth cohort, the incidence of appendiceal adenocarcinoma tripled among the 1980 birth cohort and quadrupled among the 1985 birth cohort. Looking at it another way, the age-specific incidence rate for all appendiceal adenocarcinomas increased by 3.7% per year in recent decades with the greatest increase seen for goblet cell adenocarcinomas.

Commentary 

Though rare, adenocarcinoma of the appendix can be associated with a poor outlook, despite therapeutic advances such as hyperthermic intraperitoneal chemotherapy (HIPEC). Early detection by colonoscopy or imaging can be challenging, meaning that the clinician must maintain a high index of suspicion for these rare tumors if early detection, so crucial for survival, is to occur. The increasing rate of appendiceal adenocarcinoma should also be appreciated in the context of declining rates of appendectomy and, therefore, diagnoses of incidental cancers. This study, together with other data, suggests that there is a real and significant increase in the incidence of this cancer. Birth cohort effects have been demonstrated for other cancers and prompted a search for some common exposure(s) (dietary or environmental) among the affected cohorts. It is likely that the same logic may very well apply to appendiceal adenocarcinoma but, as yet, responsible risk factors remain unknown. 

Citation

Holowatyj AN, Washington MK, Goldberg RM, Murphy CC. Birth Cohort Effects in Appendiceal Adenocarcinoma Incidence Across the United States. Ann Intern Med. 2025;178:957-962.

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