TY - JOUR
T1 - Primary Tumor Resection is Associated with Improved Disease-Specific Mortality in Patients with Stage IV Small Intestinal Neuroendocrine Tumors (NETs)
T2 - A Comparison of Upfront Surgical Resection Versus a Watch and Wait Strategy in Two Specialist NET Centers
AU - Levy, Sonja
AU - Arthur, James D
AU - Banks, Melissa
AU - Kok, Niels F M
AU - Fenwick, Stephen W
AU - Diaz-Nieto, Rafael
AU - van Leerdam, Monique E
AU - Cuthbertson, Daniel J
AU - Valk, Gerlof D
AU - Kuhlmann, Koert F D
AU - Tesselaar, Margot E T
N1 - Funding Information:
The authors thank all the patients, investigators of the study and supporting teams at both participating centers. They also thank Rob Kessels and Mutamba Kayembe for statistical coding support.
Publisher Copyright:
© 2022, Society of Surgical Oncology.
PY - 2022/11
Y1 - 2022/11
N2 - Introduction: Small intestinal neuroendocrine tumors (SI-NETs) often present with metastatic disease. An ongoing debate exists on whether to perform primary tumor resection (PTR) in patients with stage IV SI-NETs, without symptoms of the primary tumor and inoperable metastatic disease. Objective: The aim of this study was to compare a treatment strategy of upfront surgical resection versus a surveillance strategy of watch and wait. Methods: This was a retrospective cohort study of patients with stage IV SI-NETs at diagnosis, between 2000 and 2018, from two tertiary referral centers (Netherlands Cancer Institute [NKI] and Aintree University Hospital [AUH]) who had adopted contrasting treatment approaches: upfront surgical resection and watch and wait, respectively. Patients without symptoms related to the primary tumor were included. Multivariable intention-to-treat (ITT), per-protocol (PP), and instrumental variable (IV) analyses using ‘institute’ as an IV were performed to assess the influence of PTR on disease-specific mortality (DSM). Results: A total of 557 patients were identified, with 145 patients remaining after exclusion of stage I–III disease or symptoms of the primary tumor (93 from the NKI and 52 from AUH). The cohorts differed in performance status (PS; p = 0.006) and tumor grade (p < 0.001). PTR was independently associated with reduced DSM irrespective of statistical methods employed: ITT hazard ratio [HR] 0.60, p = 0.005; PP HR 0.58, p < 0.001; and IV HR 0.07, p = 0.019. Other factors associated with DSM were age, PS, high chromogranin A, and somatostatin analog treatment. Conclusion: Taking advantage of contrasting institutional treatment strategies, this study identified PTR as an independent predictor of DSM. Future prospective studies should aim to validate these results.
AB - Introduction: Small intestinal neuroendocrine tumors (SI-NETs) often present with metastatic disease. An ongoing debate exists on whether to perform primary tumor resection (PTR) in patients with stage IV SI-NETs, without symptoms of the primary tumor and inoperable metastatic disease. Objective: The aim of this study was to compare a treatment strategy of upfront surgical resection versus a surveillance strategy of watch and wait. Methods: This was a retrospective cohort study of patients with stage IV SI-NETs at diagnosis, between 2000 and 2018, from two tertiary referral centers (Netherlands Cancer Institute [NKI] and Aintree University Hospital [AUH]) who had adopted contrasting treatment approaches: upfront surgical resection and watch and wait, respectively. Patients without symptoms related to the primary tumor were included. Multivariable intention-to-treat (ITT), per-protocol (PP), and instrumental variable (IV) analyses using ‘institute’ as an IV were performed to assess the influence of PTR on disease-specific mortality (DSM). Results: A total of 557 patients were identified, with 145 patients remaining after exclusion of stage I–III disease or symptoms of the primary tumor (93 from the NKI and 52 from AUH). The cohorts differed in performance status (PS; p = 0.006) and tumor grade (p < 0.001). PTR was independently associated with reduced DSM irrespective of statistical methods employed: ITT hazard ratio [HR] 0.60, p = 0.005; PP HR 0.58, p < 0.001; and IV HR 0.07, p = 0.019. Other factors associated with DSM were age, PS, high chromogranin A, and somatostatin analog treatment. Conclusion: Taking advantage of contrasting institutional treatment strategies, this study identified PTR as an independent predictor of DSM. Future prospective studies should aim to validate these results.
KW - Chromogranin A
KW - Humans
KW - Intestinal Neoplasms/pathology
KW - Neuroendocrine Tumors/pathology
KW - Prospective Studies
KW - Retrospective Studies
KW - Somatostatin
KW - Treatment Outcome
UR - http://www.scopus.com/inward/record.url?scp=85134509243&partnerID=8YFLogxK
U2 - 10.1245/s10434-022-12030-0
DO - 10.1245/s10434-022-12030-0
M3 - Article
C2 - 35842528
SN - 1068-9265
VL - 29
SP - 7822
EP - 7832
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 12
ER -