Rosario Ligresti, MD, FASGE
Among rare and understudied tumor types lies appendiceal cancer, of which the incidence has increased since 2010 without much explanation, according to Rosario Ligresti, MD, FASGE.
In a retrospective study published in Cancer, data revealed that between 1992 and 2016, 4570 malignant appendiceal tumors were observed in patients at least 15 years of age in the Canadian Cancer Registry, and 7060 were observed in the Surveillance, Epidemiology, and End Results incidence database.1 Furthermore, data from a prospective study published in JAMA Surgery determined that a higher rate of appendiceal tumors was observed in patients with periappendicular abscesses (14.3%; 95% CI, 10.8%-17.9%) compared with those who had uncomplicated acute appendicitis (1.5%; 95% CI, 1.1%-1.9%; P < .001) and those with complicated acute appendicitis without periappendicular abscesses (2.4%; 95% CI, 1.8%-3.0%; P < .001).2 Notably, patient age was the only factor associated with the prevalence of periappendicular abscess tumors (odds ratio, 1.06; 95% CI, 1.04-1.09; P < .001).
“This reinforces the need for thinking about the rising incidence of [appendiceal cancer in] younger patients. We can tie this a little bit into colon cancer, [especially] now we’re considering screening patients at the age of 45 years or younger for colon cancer,” Ligresti explained in an interview with OncLive® for Appendiceal Cancer Awareness Month, observed annually in August. “There’s an increased incidence of colon cancer in younger populations, and this may be part of that entire shift. Why does that matter? Because sometimes [appendiceal cancer is] diagnosed at colonoscopy.”
In the interview, Ligresti highlighted the importance of spreading awareness about appendiceal cancer, common misconceptions surrounding this malignancy, current treatment approaches, and significant unmet needs that persist for this patient population.
Ligresti is the chief of gastroenterology at Hackensack University Medical Center in New Jersey.
OncLive: Why is it essential to spread awareness about appendiceal cancer?
Ligresti: Appendix cancer is one of those cancers [that’s] extremely uncommon. People don’t think about it, and when they do, it’s lumped together with colon cancer, but it’s an extremely different animal; it’s not quite colon cancer. More importantly, [appendix cancer] is increasing in incidence, very much in parallel with a lot of [other] cancers worldwide; unfortunately, it’s increasing in younger patients. For a variety of reasons, appendix cancer is not thought of often, and it’s not a commonly seen diagnosis.
Given the rarity of this cancer, what are some of the most common misconceptions oncology teams should know regarding the management of this disease?
With only about 3000 patients seen annually [with appendiceal cancer], it’s one of those cancers that, unless it’s kept in mind, it’s not kept in mind. Fifty percent of patients have no symptoms at all, and another 30% will [have it] present as appendicitis. More surgeons are treating patients with appendicitis in a nonoperative, more medical way, and that may not be the best thing [due to the rising incidence of appendix cancer].
At the end of the day, a lot of the specimens removed from [younger] patients who have appendicitis may harbor appendiceal cancer. If you see a patient who doesn’t quite fit the typical patient who should have appendicitis, [such as] a very young, otherwise healthy patient, but in someone who’s a little bit older, we should keep in mind that a [sizeable] percentage of those patients may be harboring a malignancy, like appendiceal cancer.
Besides surgery, what treatments are available?
A large percentage of these patients will present as if they have appendicitis, and it’s the same underlying causes of appendicitis that happen in nononcologic appendicitis. Patients have appendicitis for a variety of reasons, like E. faecalis, and in that group of patients, the treatment has been surgery for many years. More recently, patients are being treated more medically, which may not be in their best interest. Without a doubt, surgery still plays the primary role. Patients should have a right colonic resection to remove the tumor and the surrounding colon, if possible.
However, if patients, for example, don’t meet the criteria to [undergo] surgery, then there are certain treatments, depending on the pathology. [Approximately] 20% of these patients will have a cancer of the appendix that looks very much like colon cancer pathologically. Those patients are treated with conventional colon cancer chemotherapy. [Still,] the problem with that is that the data are very limited. [Will a] patient who has colon cancer pathology originating in the appendix [have a disease that] behaves just like colon cancer originating in the rest of the colon? That we don’t know, because there have been too few patients to study. We don’t really know if treating someone with appendiceal cancer that looks like colon cancer will respond the same way as colon cancer anywhere else.
The benefit is that there has been certainly good response in those patients when you treat them like as if they have colon cancer. The downside is that in the younger patients that we’re seeing, the pathology is shifting towards a more neuroendocrine or carcinoid type. In that particular group, there are effective chemotherapy agents that can be used, although we don’t know if they work well enough in appendiceal cancer to apply them uniformly. The mainstay of therapy is surgery, if possible; however, 50% of patients will have no symptoms until it’s too late.
Overall survival [(OS) rates] with this disease are all over the map, from dismal when the patients have no symptoms, at [approximately] 29% to 33%, all the way up [approximately] 93% if [the tumor is] found incidentally during an appendectomy. [OS] is stage-dependent, as is everything, and also pathology-dependent.
Are there any ongoing clinical trials or research in this space to address these disparities?
Unfortunately, no, and that’s the big problem with appendiceal cancer. It’s a cancer where the incidence rate is so low therefore the total population is low. What we are seeing trial-wise is a lot of epidemiological data being put forward, especially in the last 6 months. We’ve seen 2 significant reviews showing the change in demographics and in presentation of this disease to a younger population.
However, as far as etiology, that remains a little bit of a mystery. Better treatment courses are a bit of an unstudied area. We don’t know if there are any benefits in treating patients more medically or oncologically, other than performing surgery, because there are so few patients with the disease. If you look at the types of tumors that we’re seeing in younger patients, neuroendocrine tumors, especially of the appendix, or nerve tumors of the appendix, there are limited data sets in nerve tumors elsewhere, and [the appendix] is [a common] spot for nerve tumors of the gastrointestinal tract in patients. There’s a bit of a vacuum and a big paucity, which why [it’s important to bring awareness to this].
What are the main unmet needs for patients with appendix cancer, and what is needed to address them?
There are 2 big unmet needs. The biggest unmet need is [determining] how to make an early diagnosis in a patient [with appendiceal cancer]. This is where biomarkers may be important in picking out the right patient population, for example, that could be tested. Patients who are at risk for colon cancer, generally, might be a patient group that might be interesting to look at. We know that there are some trends of increasing [incidence in] appendiceal cancer in patients who have inflammatory bowel disease, like Crohn’s disease and ulcerative colitis. This could be a patient population where you might want to target some of the data that we have and evaluate patients for early detection with something like biomarker testing. There is a whole, uncharted, untapped potential for this.
The other part of figuring this out from an early detection standpoint is trying to nail down the epidemiology. Why is it that the incidence rate is increasing in younger populations? Why is there a stage shift and a pathology shift in younger populations? There isn’t a clear answer as to why someone in a younger age cohort is getting an increased incidence of carcinoid. What exactly is in the environment? What exactly is in the genome that is changing to force this? JAMA Surgery put out an article earlier this year that highlighted that patients in younger age cohorts—patients born in the late 1970s to early 1980s—had a tripling of their incidence rate, and we don’t know why, and that’s a real problem.2 The unmet needs here are [establishing if] there is a way to do early detection. More importantly, [determining] where this is all coming from.
References
- Singh H, Koomson AS, Decker KM, et al. Continued increasing incidence of malignant appendiceal tumors in Canada and the United States: a population-based study. Cancer. 2020;126(10);2206-2216. doi:10.1002/cncr.32793
- Salminen R, Alajääski J, Rautio T, et al. Appendiceal tumor prevalence in patients with periappendicular abscess. JAMA Surg. 2025;160(5):526-534. doi:10.1001/jamasurg.2025.0312