Andrea Holowatyj, PhD, MSCI delved into the growing issue of early-onset appendiceal cancer, how it impacts certain groups, and what efforts can improve outcomes for these patients in the future.
Oncologists have limited information about the risk factors and etiologies of appendiceal cancer, which is an issue considering the growing increase of early on-set cases in the United States.
Research shows that between 2006 and 2020, early-onset appendiceal cancer occurrence has increased by 232%. Based on the high increase, investigators set out to determine what factors may be contributing, including race and ethnicity. Specifically, a study used data from the Surveillance, Epidemiology, and Ed Results database to look at survival outcomes across race and ethnic subgroups of patients with appendiceal cancer.
In an interview with Targeted OncologyTM, Andreana Holowatyj, PhD, MSCI, assistant professor of Medicine and Cancer Biology, Epidemiology, delved into the growing issue of early-onset appendiceal cancer, how it impacts certain groups, and what efforts can improve outcomes for these patients in the future.
Can you talk about the rarity of this disease and how you think that impacts treatment options?
Holowatyj: Appendiceal cancer is a rare malignancy, and has an age adjusted incidence rate of about 0.12 per million person years. As a consequence of the rarity of this malignancy, there are challenges and significant advances in the discovery and understanding of risk factors disease, biology, and epidemiology. This also presents challenges in understanding disease pathogenesis, which is needed to develop clinical management guidelines. So currently, the guidelines from the National Comprehensive Cancer Network recommend a hemicolectomy followed by adjuvant chemotherapy as definitive treatment for early-stage appendiceal cancers. The guidelines are very similar to colon cancer guidelines, largely because there's a lack of robust data for appendix cancer. These treatment regimens are also extrapolated from clinical studies related to colon cancer.
What led to your study of survival outcomes in patients with early-onset appendiceal cancer in the United States?
So, there is a rising disease burden for early-onset cancers, which are cancers diagnosed among adults aged 18 to 49 years, sort of across the board. We're seeing an increased incidence of breast cancer, pancreatic cancer, multiple other obesity-related cancers. Many have likely heard about the increasing incidence of early-onset colorectal cancer, which has garnered much attention with recent recommendations to lower the screening age to 45 years for individuals at average risk.
In early 2020, there was an elegant study that was published demonstrating that among patients of all ages diagnosed with malignant appendiceal cancers, we've seen an increase of incidence rates about 232% in the United States between 2002 1016, and we're seeing some of these rates rise from older to younger generations. With my research program at Vanderbilt, we're focused on the distinct disease burden of early-onset cancers, including biology, disparities, and survivorship. So, this was an intriguing observation for us particularly given the rates of appendectomies, which often lead to a diagnosis of incidental appendix cancer remained stable over this time period. And so, we really wanted to create the field of early-onset appendix cancer to understand this distinct disease burden. One of the biggest challenges for us is that there's often a potential for misclassification of appendiceal cancer for malignancies of the colon. It's important to differentiate these malignancies that are starting to show distinct molecular characteristics and consider appendiceal cancer as its own tumor type, in order to be able to close these gaps and understand epidemiology and risk factors. The better clinical management guidelines can be developed that are specific to this population, and ultimately improve patient and clinical outcomes overall.
How was information from the SEER database used to conduct this study?
The reason we turn to the NCI’s SEER program was because we could leverage population-based cancer registry data that covers about almost a third of the United States population. That really gave us a strategic advantage when studying a rare malignancy, such as appendiceal cancer, because we were able to leverage robust and gold standard registry data from all across the country and with sufficient cases to be able to look at differences in disease patterns, as well as disease outcomes. Our observation of disparities in survival among patients with early-onset appendix cancer was able to be explored and identified with SEER.
Why was it important to strategy patients by race and ethnicity?
It’s really important for me to point out and highlight that race is a social construct. So, the use of genetic ancestry data to be able to look at differences by genetic ancestry is ideal. But in the absence of this data, we really wanted to understand whether there were disparities in survival across these groups. This really is relevant to and builds upon my previous finding in the Journal of Clinical Oncology, which shows racial-ethnic disparities and survival among young patients with colorectal adenocarcinoma. So, as a first step, we really wanted to understand were their survival disparities in this population of young patients with appendiceal cancer, and then what may be contributing to these differences in survival that we observed in subsequent studies and next steps?
Can you explain the findings of the analysis?
Our observation of disparities and survival among adults diagnosed with early-onset appendix cancer revealed that there are significantly poorer disease outcomes among nonHispanic Black individuals compared with nonHispanic Whites and among men compared with women. This was really striking to us overall because these findings really emphasize the importance of early detection and diagnosis given the rise in disease burden. And the survival difference observed by race or ethnicity among young patients with appendiceal cancer, in turn, may be partly attributed to differences in socioeconomic status by race and ethnicity, which could attribute to the variation in diagnostic or surgical procedures, such as undergoing an appendectomy versus getting antibiotic therapy for patients with acute appendicitis, or potential differences in access to health care. But findings in our study showed that young nonHispanic Blacks with early-onset appendiceal cancer have a similar socioeconomic status to young Hispanics, and presumably, experience comparable barriers, and access to health care is important because we actually observe no differences in survival between young Hispanics and young nonHispanic Whites with appendiceal cancer, which was similar to our findings in early-onset colorectal cancer.
So, although these factors may indeed impact survival rates among patients with early-onset appendiceal cancer, they certainly do not completely explain the survival difference we observed between Blacks and other racial or ethnic groups. So hopefully, in future studies, we can determine the extent to which health behaviors environmental exposures and molecular characteristics may contribute to this heterogeneity in outcomes by race and ethnicity among patients with appendiceal cancer.
Since your research was published, other studies have looked into this subject matter. What is important to highlight about these studies collectively?
I this study, as well as in our other studies, we consistently observed that in contrast to the finding that about 1 in every 10 patients diagnosed with colorectal cancer is younger than age 50, we actually see a very different demography in appendix cancer, where approximately 1 in every 3 individuals diagnosed with appendiceal cancer is younger than age 50. This is really important because it suggests that in proportion to the overall disease burden, there's a higher proportion of early-onset cases for appendiceal cancer, and really is important to consider given the young individuals have a very different challenges throughout their cancer journey and have other life domains that can be impacted by cancer diagnosis that need to be addressed overall.
From the molecular perspective, we also were able to use consortium data to explore somatic mutations and appendiceal cancer by age at disease sequencing and observed distinct molecular characteristics and tumors of individuals diagnosed with early-onset appendix cancer compared with late onset disease. This is intriguing because there's potential clinical relevance and therapeutic implications that may be seen in follow-up studies and further causal investigations to understand some of the mechanisms underlying disease pathogenesis. But overall, these studies focus on shedding light on this rare malignancy that has an increasing disease burden in really trying to not only understand disease pathogenesis, to improve clinical management and clinical care guidelines, but also to identify individuals who may be at higher risk or address care needs of individuals after this disease diagnosis and are pointing to distinct patterns of disease across age groups.
What is your key takeaway for community oncologists about early-onset appendiceal cancer?
I think the biggest takeaway and message particularly for this rare malignancy that has a growing disease burden is to consider appendix cancer as a distinct disease separate from colon cancer. The potential misclassification of appendiceal cancer as malignancies of the colon makes it challenging for us to better understand the unique molecular and clinical characteristics and patterns of this malignancy, as well as understand factors that contribute to differences in disease outcomes. By understanding that appendiceal cancer is a distinct malignancy from tumors located in the right side of the colon. This will really help us to best classify these cases and better understand the unique characteristics of this malignancy in order to translate that into significant advances clinically, therapeutically, and epidemiologically for this population.
Holowatyj AN, Washington KM, Salaria SN, et al. Early-onset appendiceal cancer survival by race or ethnicity in the United States. Gastroenterology. 2021;159(4):1605-1608. doi: 10.1053/j.gastro.2020.06.011.