A Staged Approach Offers Benefits Without OS Detriment in Appendix Cancers

Resection after appendectomy should be prioritized in the treatment of patients with appendiceal cancer, according to a study presented at SSO 2025.

Muhammad Talha Waheed, MD, a postdoctoral research fellow at City of Hope Comprehensive Cancer Center in Duarte, California, and fellow investigators found that a staged approach—initial appendectomy followed by resection—did not lead to decreased overall survival (OS) and should be considered more favorably when compared with upfront right colectomy.

Waheed spoke with CancerNetwork® before the 2025 Society of Surgical Oncology Annual Meeting about a poster he presented on the differences in outcomes between the 2 approaches in patients with appendiceal cancer.

Of appendectomy alone, upfront colectomy, and staged colectomy, the best survival was observed with the staged colectomy (vs appendectomy alone; HR, 0.52; 95% CI, 0.34-0.80; P = .003); the upfront colectomy approach demonstrated the worst survival (vs staged colectomy; HR, 2.13; 95% CI, 1.42-3.16; P <.001). In a matched cohort, patients who received staged colectomy had comparable adjusted survival probabilities vs upfront colectomy both before (HR, 1.26; 95% CI, 0.55-2.87; P = .587) and after (HR, 1.25; 95% CI, 0.55-2.85; P = .589) propensity matching.

Additionally, 26% of patients received appendectomy alone, and 74% received any colectomy, 48% of whom received upfront colectomy and 52% received staged colectomy. Appendectomy alone occurred more frequently in patients older than 80 years (16%), with a Charlson-Deyo score of 2 or higher (19%), and with Medicare insurance (36%).

“The number one thing that we do anticipate is that the NCCN guidelines for appendiceal cancers, which are in development, will likely reduce the underutilization of right colectomy and may also bring homogeneity in the treatment of appendix cancers,” Waheed concluded.

CancerNetwork: Why did so many patients—26%—opt not to undergo resection after appendectomy, and why was this relevant?

This underutilization of right colectomy after appendectomy is a key finding. It’s a cause of concern because although some large databases do support appendectomy alone in certain clinical scenarios for appendiceal adenocarcinomas—for example, in the setting of appendiceal adenocarcinomas or well-differentiated mucinous appendiceal carcinomas— The Chicago Consensus Guidelines or the [American Society of Colon and Rectal Surgeons] guidelines do recommend a right hemicolectomy for appendiceal adenocarcinomas. That [prompted] us to ask if there is a risk vs benefit question that is going on. Do these patients have more comorbidities or sickness? Is that why these patients didnot undergo colectomy? When we looked at it, [more] patients underwent appendectomy alone and had no or minimal reported comorbidities. This underutilization remained very high in patients treated at Commission on Cancer [CoC]-accredited hospitals.

We speculate that this could be because of a lack of consensus guidelines for appendiceal adenocarcinomas up until recently. It could be because of a loss of follow-up, or maybe these patients were traveling out of state, got their first resection, and went back, traveled, and got their resection out of state. We were not able to capture that. Regardless, this should be explored further. We should advocate for these patients to get a definite resection if needed.

The staged approach was not detrimental to OS. What does that mean for appendiceal cancer treatment standards?

It means that there should be a conversation about the optimal sequence of resection. Currently, there are no national Academic Research Consortium [ARC] consensus guidelines that guide us regarding the optimal sequence of resection for these patients. The decision to perform an upfront colectomy or a staged colectomy is solely at that surgeon’s discretion depending on the level of suspicion that the surgeon has. Unfortunately, given the rarity of appendix cancers, it is almost impossible to conduct [randomized] clinical trials to look at the optimal sequence. Most of these data are guided by retrospective studies such as ours. Historically, a major concern with the staged approach is that it separates a primary resection and the lymphadenectomy, which could potentially result in detrimental survival for patients who receive staged colectomy. But with these findings that we have now, we’ve reported that we do not see any differences in OS, and the benefits do outweigh the risks here. Hence, the staged colectomy should be preferred. This should be picked up by consensus groups, and it should be a topic of discussion at these consensus meetings to help guide the surgeons forward.

Beyond OS, what are some benefits observed with the staged approach vs the upfront approach?

Appendiceal malignancies are often diagnosed in emergency settings when patients undergo appendectomy for suspected appendicitis. The intraoperative frozen section is also very unreliable to subtype the appendiceal neoplasm. Even with permanent pathology, expert appendicealcancer pathologists change their diagnosis around 20% of the time. At the end of the day, 26% to 33% of appendiceal neoplasmsmay turn out to be localized mucinous neoplasms or benign neuroendocrine tumors, where appendectomy alone may be the only operation that you need. Compared to appendectomy, colectomy is a more invasive procedure; it may be associated with higher comorbidity, increased unplanned readmissions, and prolonged length of stay compared to appendectomy alone. It should be avoided if not needed or indicated. If you do not need it for the histologic subtype that you have on hand, you should not be doing it. All of this could be avoided if a standard resection is planned for a subset of patients.

How might the staged approach give patients the ability to access histologic assessments and referrals to expert centers while sparing the morbidity of a hemicolectomy?

For prognosis, appendiceal neoplasms are predominantly dependent or determined by the histologic subtype that you have—the grade and the stage. Moreover, even though the histologic classification is very challenging to discern, it remains the cornerstone of clinical decision-making for the surgeon. For example, similar to gallbladder cancer, we do not have the liberty of conducting a biopsy and knowing the subtype beforehand. That is why, with staged colectomy, you’re putting a gap between the diagnosis by doing an appendectomy first and then planning your definitive resection later. It allows enough time in between to have the information that you need and plan the best course of action for those patients. For example, it will allow an expert pathologist to review and subtype the histology. Given the rarity of appendiceal cancers, some centers may not be experienced in treating them, so it allows the patient to seek care at an expert, high-volume center for their definitive resection. Very importantly, if the pathology turns out to be either benign or localized mucinous neoplasm, and, for example, if the initial resection had negative margins, you may not need to do anything. You are sparing them a morbid operation which could have substantially impacted their quality of life.

What are some of the next steps for research?

Our research, at this point, has been conducted on the California Cancer Registry, which is the statewide registry…It’s hard to extrapolate these results nationwide. The next steps would be to look at these trends nationally using national cancer databases. Moreover, there has to be stronger advocacy and discussion on this topic, and the upcoming consensus guidelines [need] to guide these surgeons on the optimal sequence of their resection. We would also like to see other groups report their experiences, and, eventually, for those data to be picked up and combined [with] the consensus guidelines. [That way, we] have a clear pathway to guide the surgeons in treating this difficult disease. The number one thing that we do anticipate is that the NCCN guidelines for appendiceal cancers, which are in development, will likely reduce the underutilization of right colectomy and may also bring homogeneity in the treatment of appendix cancers.

Reference

Waheed MT, Malik I, Ituarte PHG, et al. Upfront colectomy vs. initial appendectomy followed by completion colectomy for appendiceal cancer: comparison of outcomes. Presented at the 2025 Society of Surgical Oncology Annual Meeting; March 27-29, 2025; Tampa, FL.