Surgery Provides Long-Term Survival in Patients with Metastatic Neuroendocrine Tumors Undergoing Resection for Non-Hormonal Symptoms
Patients with metastatic neuroendocrine tumor (NET) often have an indolent disease course yet the outcomes for patients with metastatic NET undergoing surgery for non-hormonal (NH) symptoms of GI obstruction, bleeding, or pain is not known.
We identified patients with metastatic gastroenteropancreatic NET who underwent resection from 2000 to 2016 at 8 academic institutions who participated in the US Neuroendocrine Tumor Study Group.
Of 581 patients with metastatic NET to liver (61.3%), lymph nodes (24.1%), lung (2.1%), and bone (2.5%), 332 (57.1%) presented with NH symptoms of pain (n = 223, 67.4%), GI bleeding (n = 54, 16.3%), GI obstruction (n = 49, 14.8%), and biliary obstruction (n = 22, 6.7%). Most patients were undergoing their first operation (85.4%) within 4 weeks of diagnosis. The median overall survival was 110.4 months, and operative intent predicted survival (p < 0.001) with 66.3% undergoing curative resection. Removal of all metastatic disease was associated with the longest median survival (112.5 months) compared to debulking (89.2 months), or palliative resection (50.0 months; p < 0.001). The 1-, 3-, and 12-month mortality was 3.0%, 4.5%, and 9.0%, respectively. Factors associated with 1-year mortality included palliative operations (OR 6.54, p = 0.006), foregut NET (5.62, p = 0.042), major complication (4.91, p = 0.001), and high tumor grade (11.2, p < 0.001). The conditional survival for patients who lived past 1 year was 119 months.
Patients with metastatic NET and NH symptoms that necessitate surgery have long-term survival, and goals of care should focus on both oncologic and quality of life impact. Surgical intervention remains a critical component of multidisciplinary care of symptomatic patients.
KeywordsNeuroendocrine tumor Metastatic Non-hormonal Symptoms Palliative surgery
Study Design: Jeffery Chakedis, Eliza W. Beal, Timothy M. Pawlik, Carl R. Schmidt, Mary Dillhoff.
Data Acquisition: Jeffery Chakedis, Eliza W. Beal, Alexandra G. Lopez-Aguiar, George Poultsides, Eleftherios Makris, Flavio G. Rocha, Zaheer Kanji, Sharon Weber, Alexander Fisher, Ryan Fields, Bradley A. Krasnick, Kamran Idrees, Paula Marincola-Smith, Clifford Cho, Megan Beems, Timothy M. Pawlik, Shishir K Maithel, Carl R. Schmidt, Mary Dillhoff.
Data Analysis/Interpretation: Jeffery Chakedis, Eliza W. Beal, Carl R. Schmidt, Mary Dillhoff.
Manuscript Preparation/Approval: Jeffery Chakedis, Eliza W. Beal, Alexandra G. Lopez-Aguiar, George Poultsides, Eleftherios Makris, Flavio G. Rocha, Zaheer Kanji, Sharon Weber, Alexander Fisher, Ryan Fields, Bradley A. Krasnick, Kamran Idrees, Paula Marincola-Smith, Clifford Cho, Megan Beems, Timothy M. Pawlik, Shishir K Maithel, Carl R. Schmidt, Mary Dillhoff.
Compliance with Ethical Standards
The institutional review board from each institution approved the study
Conflict of Interest
The authors declare that they have no conflict of interest.
- 4.Rinke A, Muller HH, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol. 2009;27(28):4656–4663.CrossRefGoogle Scholar
- 15.Sarmiento JM, Heywood G, Rubin J, Ilstrup DM, Nagorney DM, Que FG. Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg. 2003;197(1):29–37.Google Scholar
- 17.Pavel ME, Singh S, Strosberg JR, et al. Health-related quality of life for everolimus versus placebo in patients with advanced, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (RADIANT-4): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18(10):1411–1422.CrossRefGoogle Scholar
- 28.Kulke MH, Shah MH, Benson AB, 3rd, et al. Neuroendocrine tumors, version 1.2015. J Natl Compr Canc Netw. 2015;13(1):78–108.Google Scholar
- 45.Gulec SA, Mountcastle TS, Frey D, et al. Cytoreductive surgery in patients with advanced-stage carcinoid tumors. Am Surg. 2002;68(8):667–671; discussion 671-662.Google Scholar