Adjuvant therapy following resection of gastroenteropancreatic neuroendocrine tumors provides no recurrence or survival benefit

• Authors: James R. Barrett, University of Wisconsin-Madison; Victoria Rendell, University of Wisconsin-Madison; Courtney Pokrzywa, University of Wisconsin-Madison; Alexandra G. Lopez-Aguiar, Emory University; John Cannon, Stanford University; George A. Poultsides, Stanford University; Flavio Rocha, Virginia Mason Medical Center; Angelena Crown, Virginia Mason Medical Center; Eliza Beal, Ohio State University; Timothy Michael Pawlik, Ohio State University; Ryan Fields, Washington University St. Louis; Roheena Z. Panni, Washington University St. Louis; Paula Smith, Vanderbilt University; Kamran Idrees, Vanderbilt University; Clifford Cho, University of Michigan; Megan Beems, University of Michigan; Shishir Maithel, Emory University; Sharon Weber, University of Wisconsin-Madison; Daniel Erik Abbott, University of Wisconsin-Madison
• Journal Title: Journal of Surgical Oncology
• Volume: Volume 121, Number 7
• Publisher: John Wiley & Sons, Inc. | 2020-06-01, Pages 1067-1073
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/jso.25896
• Subjects: Health Sciences, Rehabilitation and Therapy; Health Sciences, Oncology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; Surgery; combined therapies; retrospective review; US Neuroendocrine Tumor Study Group; Gastrointestinal tract; Aggressive surgery; Prognostic factors; Interferon-alpha; Metastasis; Management

Abstract

Background and Objectives Lack of high-level evidence supporting adjuvant therapy for patients with resected gastroenteropancreatic neuroendocrine tumors (GEP NETs) warrants an evaluation of its non-standard of care use. Methods Patients with primary GEP NETs who underwent curative-intent resection at eight institutions between 2000 and 2016 were identified; 91 patients received adjuvant therapy. Recurrence-free survival (RFS) and overall survival (OS) were compared between adjuvant cytotoxic chemotherapy and somatostatin analog cohorts. Results In resected patients, 33 received cytotoxic chemotherapy, and 58 received somatostatin analogs. Five-year RFS/OS was 49% and 83%, respectively. Cytotoxic chemotherapy RFS/OS was 36% and 61%, respectively, lower than the no therapy cohort (P <.01). RFS with somatostatin analog therapy (compared to none) was lower (P <.01), as was OS (P =.01). On multivariable analysis, adjuvant cytotoxic therapy was negatively associated with RFS but not OS controlling for patient/tumor-specific characteristics (RFS P <.01). Conclusions Our data, reflecting the largest reported experience to date, demonstrate that adjuvant therapy for resected GEP NETs is negatively associated with RFS and confers no OS benefit. Selection bias enriching our treatment cohort for individuals with unmeasured high-risk characteristics likely explains some of these results; future studies should focus on patient subsets who may benefit from adjuvant therapy.