Appendiceal Cancer Linked to Increased Secondary Cancer Risk

Pancreatic cancer, 3D rendering: © matthieu - stock.adobe.com

In adults diagnosed with a first primary appendiceal adenocarcinoma, approximately 1 in 13 patients in the US will develop a second primary cancer within 10 years. Additionally, there is a 12% higher-than-expected incidence of secondary primary cancers, including colorectal cancers, compared to the general population, according to data presented at the 2025 ASCO Gastrointestinal Cancers Symposium.¹

Furthermore, the study underscores the importance of implementing robust cancer prevention and early detection strategies for individuals diagnosed with appendiceal adenocarcinoma. These strategies, which include interventions such as colonoscopy screening and genetic testing, are identified as a critical clinical priority, according to the study.

“Incidence rates of rare appendiceal cancers are increasing across the United States. Although this is suggestive of a growing population of appendiceal cancer survivors over time, the risk of second primary cancers specific to patients with a first primary appendiceal adenocarcinoma remains unknown,” Andreana N Holowatyj, PhD, MSCI, an assistant professor of medicine in the Division of Epidemiology and Cancer Biology at Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, in Nashville, Tennessee, and co-authors wrote in the abstract of their presentation.

Holowatyj also serves as research director and co-director of the Research Immersion Course at the Vanderbilt University School of Medicine..

The cumulative incidence of second primary cancer was 7.5% (95%CI, 6.8%-8.4%) and 11.7% (95%CI, 10.5%-12.9%), at 10 and 20 years after appendiceal adenocarcinoma diagnosis, respectively. The cumulative incidence was significantly different between sexes (P < 0.01) and age at the diagnosis of appendiceal adenocarcinoma (early-onset [age < 50] vd late-onset; P < 0.01).¹

For instance, at a 10-year post-diagnosis, the cumulative incidence of second primary cancer for women was 6.4% (95%CI, 5.4%-7.4%) and for males was 8.8% (95%CI, 7.6%-10.1%). The overall standardized incidence ratio (SIR) for any second primary cancer was 1.12 (95% CI, 1.02-1.23), which as the study states, corresponds to an excess of 14.8 cancers per 10,000 person-years. SIRs for common types of second primary cancers included: 1.07 (95% CI, 0.84-1.35) for prostate cancer, 2.12 (95% CI, 1.63-2.70) for colorectal cancer, 0.91 (95% CI, 0.68-1.19) for female breast cancer, 0.81 (95% CI, 0.58-1.09) for lung cancer, and 1.20 (95% CI, 0.79-1.73) for melanoma.

During the trial, a total of 5,827 adults diagnosed with a first primary appendiceal adenocarcinoma (mean age, 58.0 years) were identified during the trial period. Of those identified, 418 developed a second primary cancer (51.8% female; 68.5% non-Hispanic White). The most common types of second primary cancer were prostate cancer (17.7%), colorectal cancer (14.4%), female breast cancer (10.5%), lung cancer (8.4%), and melanoma (6.0%).

A population-based study was conducted using data from the Surveillance, Epidemiology, and End Results (SEER) Program, evaluating adults (≥ 18 years) diagnosed with first primary appendiceal adenocarcinoma from 1992 to 2021. Cumulative incidence of second primary cancer, defined as any primary cancer occurring 3 months or more after appendiceal adenocarcinoma, was estimated using Fine and Gray methods to account for the competing risk of death. SIRs were calculated to compare the observed number of second cancers with the expected number, based on age-, sex-, and race-specific incidence rates in the general population.

Appendiceal cancer originates in the appendix, a small pouch in the abdomen, with two main types: epithelial and neuroendocrine. Epithelial cancers may produce mucin, causing pseudomyxoma peritonei, while neuroendocrine tumors arise from enterochromaffin cells. Cancer may spread within the abdomen or, less commonly, through lymph nodes to other areas.²

References:

1. Holowatyj A, Goldberg R, Washington M, et al. Risk of second primary cancer among patients with a first primary appendiceal adenocarcinoma. J Clin Oncol. 2025;43(suppl 4):819. doi:10.1200/JCO.2025.43.4_suppl.819

2. Appendiceal cancer (rare digestive system tumors). Pediatric and Adult Rare Tumor Network. National Cancer Institute. Accessed January 24, 2025. https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-digestive-system-tumors/appendiceal-cancer.