Resection of the Primary Tumor vs. Systemic Treatment Alone for Patients With Small Intestinal Neuroendocrine Tumors and Unresectable Metastases: a Europe-wide Study (ENETSSurgSmInt)

Resection of the Primary Tumor vs. Systemic Treatment Alone for Patients With Small Intestinal Neuroendocrine Tumors and Unresectable Metastases: a Retrospective, Europe-wide, Pooled Cohort Study (ENETS-SurgSmInt)

When possible, surgery to completely remove small intestinal neuroendocrine tumors (siNETs) is always recommended. However, in cases where the tumor has spread and cannot be cured completely, it is unclear whether a surgical removal of the primary tumor only is reasonable. In this situation, current guidelines from the European Neuroendocrine Tumor Society (ENETS) recommend surgery only for patients who have symptoms like intestinal blockage or bleeding, or are at risk of such complications. For patients without symptoms, it is still unclear whether removing the main tumor improves overall outcomes and prevents future problems.

Studies evaluating this type of surgery on survival show conflicting results. These studies often do not separate patients with symptoms from those without, and they overlook other important factors like the amount of cancer in the liver and nearby tissues. Due to these uncertainties, the rarity of siNETs and many factors that can affect outcomes, like age, overall health, or other current treatments, conducting a high-quality study to answer this question is challenging. To address this, the present Europe-wide study is being planned.

This study aims to determine if resecting the main tumor improves the 10-year overall survival and reduces risks like intestinal blockages or blood flow issues compared to no surgery in patients without symptoms. The study will also assess other outcomes, such as how long patients stay free from disease progression, the risks of surgery, and prognostic factors for long-term survival. This international collaboration among neuroendocrine tumor referral centers will provide robust evidence to guide clinical practice and update treatment guidelines for siNETs.

Study Overview

• Status: Recruiting
• Conditions: Metastasis; Bowel Obstruction; Neuroendocrine (NE) Tumors
• Intervention / Treatment: Other: Histopathological review

• Study Type: Observational
• Enrollment (Estimated): 3200

Contacts and Locations

• Study Contact: Name: Eliane Dohner; Phone Number: 0041 31 664 28 31; Email: eliane.dohner@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • UHI Berne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The investigators will include all patients with siNET and non-curative metastatic disease between 01.01.2005 and 31.12.2021.

Description

Inclusion Criteria:

- All patients with siNET and non-curative metastatic disease between 01.01.2005 and 31.12.2021 will be included.

Exclusion Criteria:

- All patients with siNET G3, resectable metastatic disease and/or non-resectable primary tumor at initial diagnosis will be excluded. Furthermore, symptomatic patients (small intestinal obstruction, bleeding) or when imaging suggests that obstruction will probably occur (bowel dilatation, mesenteric fibrosis) at initial diagnosis will be excluded. Patients with diarrhea, flushing, or abdominal pain will not be excluded.

Patients with a documented rejection for a further use of their data for scientific purposes will also be excluded.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Histopathological review; The patients will be grouped according to whether a primary tumor resection within 6 months after initial diagnosis was performed (yes vs. no).	Other: Histopathological review; Histopathological review

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the 10-year overall survival of non-curative metastatic siNET with or without primary tumor resection at initial diagnosis in asymptomatic patients.	For the survival analysis, Kaplan-Meier method will be used to estimate overall survival at 10 years for patients with and without primary tumor resection.	10 years follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the progression-free survival of non-curative metastatic siNET with or without primary tumor resection at initial diagnosis in asymptomatic patients.	For the survival analysis, Kaplan-Meier method will be used to estimate overall survival at 10 years for patients with and without primary tumor resection.	10 years follow-up
To examine the risk of small intestinal obstruction with or without palliative primary tumor resection	To account for additional established prognostic information, univariable and multivariable Cox proportional hazards regression will be used.	10 years follow-up
To examine the risk of small intestinal hypoperfusion with or without palliative primary tumor resection	To account for additional established prognostic information, univariable and multivariable Cox proportional hazards regression will be used.	10 years follow-up
To evaluate the morbidity of palliative primary tumor resection	To account for additional established prognostic information, univariable and multivariable Cox proportional hazards regression will be used.	10 years follow-up
To evaluate the mortality of palliative primary tumor resection	To account for additional established prognostic information, univariable and multivariable Cox proportional hazards regression will be used.	10 years follow-up
To assess prognostic factors for long-term survival	The following prognostic information will be taken into account: age, sex, ECOG, presence of second malignancy, and adjusted for characteristics of the siNET (Ki-67 index, number of siNETs, lymph node metastases, TBS, extrahepatic metastases, CgA level, 5-HIAA level, carcinoid heart disease, and use of other treatments), with results presented as adjusted hazard ratios (HRs) and 95% CI.	10 years follow-up

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Reto M. Kaderli, Insel Gruppe AG, University Hospital Bern

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2026
• Primary Completion (Actual): March 9, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: January 7, 2025
• First Submitted That Met QC Criteria: January 15, 2025
• First Posted (Actual): January 22, 2025

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms; Neoplasm Metastasis; Intestinal Obstruction
• Other Study ID Numbers: ENETSSurgSmInt

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No