PHILADELPHIA — When predicting lymph node metastasis in appendiceal, well-differentiated neuroendocrine tumors (WDNETs), researchers here suggested a tumor size threshold of 10 mm compared with the traditional 20 mm.
WDNETs between the size of 11 mm to 20 mm had higher rates of lymph node involvements compared to those ≤10 mm, following adequate dissection of 12 or more lymph nodes (56.8% versus 11.6%, P<0.001), according to Amir Mehrvarz Sarshekeh, MD, of the MD Anderson Cancer Center in Houston, and colleagues.
Similarly findings were reported for mixed histology tumors (MHTs) between 11-20 mm in size (32.9% versus 10.4%, P=0.004), they reported in a presentation at the North American Neuroendocrine Tumor Society annual symposium.
“Neuroendocrine tumors of appendix are usually found incidentally during appendectomy,” Mehrvarz Sarshekeh and co-author Arvind Dasari, MD, also of MD Anderson, said jointly in an email to MedPage Today. “At that time, clinicians usually face a challenge to consider appendectomy sufficient or to proceed with right hemicolectomy. The decision is usually based on the risk of regional lymph node involvement and/or metastatic disease. Tumor size is the principal factor and cut-off of 20 mm for right hemicolectomy has been accepted to formulate our treatment guidelines.
“This cut-off is based on small retrospective studies performed on carcinoid tumors of appendix,” they continued. “Since the sub-classification of appendiceal carcinoid tumors in 2010, the cut off has not been validated in different histologic subtypes and in large population-based databases. Also, the outcomes of right hemicolectomy in regionally advanced disease is unclear.”
The authors collected data on 1,731 patients from the SEER database, classified by histology codes. The analysis included 860 WDNET cases (38.0%), which mostly comprised of low-grade neuroendocrine tumors. A total of 1,659 MHT cases were assessed (60.8%) — which had tumors with both neuroendocrine and epithelial components — consisting of goblet cell carcinoid, mixed adenoneuroendocrine carcinoma, and adenocarcinoid tumors. Poorly-differentiated neuroendocrine carcinomas (PDNECs) accounted for 1.2% of appendiceal NET subtypes included (n=26).
Node-positive disease was defined in the study as any pathologic lymph node involvement, while node-negative disease was classified as no involvement after a surgical assessment of at least 12 lymph nodes. A total of 19.2% of all patients had lymph node involvement.
In a comparison of tumor subtypes, patients with WDNETs tended to be younger than those with MHT (median age 42 versus 56, P<0.001). MHT patients tended to have more distant metastases compared to WDNET cases (12.3% versus 4.8%, P<0.001).
Among the appendiceal NET histologic subtypes, 10-year cancer-specific survival rates were as follow:
- WDNETs: 92.6%
- MHTs: 78.1%
- PDNECs: 0%
In an adjusted multivariable analysis, the following characteristics were significant (all P<0.001) in association with poorer cancer-specific survival in cases without any distant metastases:
- MHT vs WDNET: HR 15.77 (95% CI 6.81-36.53)
- Age >65 at diagnoses: HR 2.18 (95% CI 1.42-3.36)
- Node involvement: HR 11.41 (95% CI 7.64-17.04)
However, the type of surgery — right hemicolectomy versus simple appendectomy — was not tied to cancer-specific survival (HR 1.12, 95% CI 0.72-1.73, P<0.62).
“We also observed that patients with regionally advanced well-differentiated neuroendocrine tumors have favorable prognosis regardless of type of surgery, while patients with mixed histology tumors with lymph node involvement had significantly worse survival compared to well differentiated neuroendocrine tumors,” Mehrvarz Sarshekeh and Dasari stated. “Our study confirms the findings of smaller studies with regards to risk of lymph node involvement and further builds on them by adding on the survival data.”
In terms of future research, the authors recommended studies that would confirm and validate their findings utilizing databases, and that “carefully designed prospective studies in both histological subtypes” are needed as well, they suggested.
“Also, the role of adjuvant therapy in mixed histology tumors needs to evaluated,” they said. “Until then, the need for right hemicolectomy in patients with well differentiated appendiceal neuroendocrine tumors should be personalized.”
No funding information was provided. Sarshekeh reported no relevant conflicts of interest.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner