The effect of prophylactic surgery in survival and HRQoL in appendiceal NEN

Abstract

Background/aims Long-term outcomes are understudied in patients with well-differentiated appendiceal neuroendocrine neoplasms (WD-ANENs). We aimed to evaluate the validity of currently applied criteria for completion prophylactic right hemicolectomy (pRHC) and determine its association with patient outcomes, including health-related quality of life (HRQoL). Methods Eligible patients from five European referral centers were divided between those who underwent appendectomy alone and those who underwent completion pRHC. HRQoL EORTC-QLC-C30 questionnaires and cross-sectional imaging data were prospectively collected. Age- and sex-matched healthy controls were recruited for HRQoL analysis’ validation. Results We included 166 patients (119 women [71.2%]: mean age at baseline: 31 ± 16 years). Mean follow-up was 50.9 ± 54 months. Most patients (152 [92%]) had tumors ≤20 mm in size. Fifty-eight patients (34.9%) underwent pRHC that in final analysis was regarded as an overtreatment in 38/58 (65.5%). In multivariable analysis, tumor size >20 mm was the only independent predictor for lymph node (LN) involvement (p = 0.002). No mortality was reported, whereas 2-, 5- and 10-year recurrence-free survival in patients subjected to postoperative cross-sectional imaging (n = 136) was 98.5%, 97.8%, and 97.8%, respectively. Global HRQoL was not significantly impaired in patients with WD-ANEN compared with age- and sex-matched healthy individuals (median scores 0.83[0.08−1] vs 0.83[0.4−1], respectively; p = 0.929). Among patients with WD-ANEN impaired social functioning (p = 0.016), diarrhea (p = 0.003) and financial difficulties (0.024) were more frequently reported in the pRHC group. Conclusions WD-ANEN is a low-malignant neoplasm with unconfirmed associated mortality, low recurrence rate, and overall preserved HRQoL. pRHC comes at a price of excessive surgery, functional HRQoL issues, and diarrhea. The value per se of a prophylactic surgical approach to patients with WD-ANENs <20 mm is challenged.

International Society of Paediatric Surgical Oncology (IPSO) Surgical Practice Guidelines

“…However, the most recent guidelines for the treatment of NETs of the appendix in adults [ 16 – 18 ] recommend RHC not only for tumours larger than 2 cm but also for incompletely excised tumours of any size, for tumours located at the base of the appendix and for cases presenting vascular invasion or extension into periappendiceal fat. Some authors actually question the need of RHC in case of either vascular invasion or extension into the periappendiceal fat [ 19 , 21 – 27 ] because in their series no correlation with the presence of distant metastases was observed.…”

European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for appendiceal neuroendocrine tumours (aNET)

“…Appendiceal NET constitute about 45%-77% of all appendiceal neoplasms. 2,[5][6][7][8][9][10][11] Appendiceal NET are more frequently found in women, ranging between 55% and 70% in different studies. 5,7,8,[10][11][12] The median age at diagnosis is 25-40 years, with a range of 4-95 years.…”

Management of incidentally discovered appendiceal neuroendocrine tumors after an appendicectomy

“…Tumor size: Some recent studies suggest that size is the main factor related to the occurrence of LNM[ 1 , 8 , 15 , 29 , 30 ]. As stated above, controversy arises in aNETs that are greater than 2 cm and those from 1 to 2 cm, which represent from 3% to 7% and from 20% to 25% of cases, respectively[ 8 , 28 ].…”

“…Although several studies agree that 2 cm is a reliable cut-off point for a colectomy, others have shown that a simple appendectomy offers comparably good results in tumors > 2 cm[ 29 ]. For example, in the classic work by Moertel et al [ 42 ], only one patient treated with an appendectomy out of 12 experienced recurrence, and it occurred 29 years after the initial appendectomy.…”

“…In addition to questions regarding a survival benefit after CRH in aNETs < 2 cm, its influence on patients’ quality of life must also be considered. This topic has recently been evaluated in a multicenter study from five ENETS centers of excellence in which the health-related quality of life European Organization for Research and Treatment of Cancer-QLC-C30 was administered to 79 patients with aNET[ 29 ]. While the patient group did not have lower scores compared to matched healthy controls, patients who underwent CRH (30 patients) had worse scores on social functioning, diarrhea, and financial difficulties compared to patients treated only with an appendectomy (49 patients).…”