Appendiceal cancer (AC) is a rare and little-understood malignancy, but one whose incidence increased in the U.S. by 232% from 2000 to 2016. It also appears to have differential survival rates according to race/ethnicity.
Yet rates of appendectomy, a procedure that often leads to incident AC diagnosis, have remained stable over this period. This cancer's rarity has resulted in sparse data and few therapeutic advances, with treatments extrapolated from colon cancer regimens and little drug development interest from pharmaceutical companies.
In the first study of its kind in AC, recently published online in Gastroenterology, Andreana N. Holowatyj, PhD, MS, of Vanderbilt University Medical Center in Nashville, and colleagues used the Surveillance, Epidemiology, and End Results (SEER) database to identify the race and ethnicity of 1,652 patients ages 20 to 49 with AC diagnosed from 2000-2011. The 5-year overall survival rate after early-onset diagnosis was noticeably lower in non-Hispanic Black patients: 63% versus 75.5% for non-Hispanic whites and 75.4% for Hispanics (P=0.001).
The 5-year cancer-specific survival rate was 64.5% for non-Hispanic Black patients versus 77.0% and 79.2% for the other two groups, respectively (P=0.0006).
Holowatyj discussed the study's findings in the following interview.
What is the general context in which you undertook this study? It seems particularly germane in light of recent healthcare realities that have come to light during the pandemic.
Holowatyj: Among patients of all ages diagnosed with AC, incidence rates have increased while rates of appendectomy have remained stable. Together with the potential for misclassification of AC cases as malignancies of the colon, these data led us to raise questions as to what causes may underlie the changing epidemiology and rising burden of AC among patients younger than 50.
Our population-based study of early-onset AC patterns, and discovery of disparities in survival across racial/ethnic groups and sex within this patient population, noticeably parallels the unequivocal burden of COVID-19 by race or ethnicity and sex. Amid the ongoing pandemic, these emerging and alarming healthcare realities heighten the urgent need to propel scientific discovery and our understanding of contributory factors to disparities in disease susceptibility and prognosis in order to mitigate these differences, particularly for non-Hispanic Black individuals.
How common is this type of cancer and what are the known risk factors, if any? Does it present as appendicitis?
Holowatyj: AC is a rare malignancy, with an age-adjusted incidence rate of 0.12 per 1,000,000 person-years. Consequently, little is known about the risk factors and etiologies specific to this disease. AC cases are usually discovered in an acute situation -- appendiceal tumors are incidentally found in nearly 10% of cases operated on -- often presenting as appendicitis. While obesity and age have been reported to be significant predictors of pathological cancer diagnosis after appendectomy, there is insufficient evidence at this time for a formal evaluation of the role of obesity on AC risk and outcomes.
Were you surprised in any way at the findings overall?
Holowatyj: Our observation of disparities in survival, with significantly poorer disease outcomes among non-Hispanic Blacks compared with non-Hispanic whites and men compared with women, were striking. Although emerging evidence is shedding light on molecular differences between colorectal and appendiceal tumors, it is disappointing that these results are concordant with disparities in survival we've previously reported among young patients with colorectal adenocarcinomas. Together, these findings emphasize the importance of early detection and diagnosis among young patients with gastrointestinal malignancies, given the rising disease burden with unknown causes and marked differences in survival between early-stage and late-stage disease.
What are some of the reasons why non-Hispanic Black patients might have poorer AC survival?
Holowatyj: The survival difference may be partly attributed to differences in socioeconomic status by race or ethnicity leading to variation in diagnostic and surgical procedures for acute appendicitis or to differential access to healthcare. But our study found that young non-Hispanic Blacks with early-onset AC have similar socioeconomic status to young Hispanics, and presumably experience comparable barriers in access to healthcare. However, we observed no differences in survival between young Hispanics and non-Hispanic whites with AC, which was similar to our findings in early-onset colorectal cancer. Although these factors may impact survival rates, they don't completely explain the survival difference between non-Hispanic Blacks and other racial or ethnic groups. Our ongoing studies aim to determine the extent to which health behaviors and potential environmental exposures, genetics, and gene-environment interactions may contribute to this heterogeneity in disease susceptibility, as well as survival, by race/ethnicity among AC patients.
Is there a clinical takeaway message emerging from these population findings?
Holowatyj: Given the alarming increase in AC incidence with undetermined causes and marked disparities in disease outcomes among young patients, it's paramount to accurately diagnose and distinguish these malignancies. And given the trend toward more non-operative management of appendicitis, gastroenterologists and surgeons should keep occult AC tumors in the differential diagnosis of young patients presenting in this manner and possibly have a lower threshold for performing appendectomy to exclude malignancy. The potential misclassification of AC as colon cancer is a barrier to discovering disease-specific risk factors and tumor biomarkers, which would have implications for AC risk assessment, screening, and surveillance, as well as treatment.
How will these findings help move the picture forward and do you plan on further studies?
Holowatyj: As the first reporting of AC patterns and outcomes among young patients, this study sheds light on the unique burden of AC in individuals younger than 50 years at diagnosis. Importantly, these findings emphasize that these cancers should not be conflated with those of cecal origin, particularly in tumor registries, and establish the basis for our current studies, which are centered on discovering additional risk factors for AC, as well as distinct clinical and molecular features of early-onset disease. Together, these findings may inform our understanding as to why early-onset AC has dramatically risen over the past 2 decades, and what behaviors we can effectively modify to reduce disease incidence and improve prognostic outcomes.