What are Neuroendocrine Tumors?
​Neuroendocrine tumors (NETs) are rare tumors that arise from hormone-producing cells found throughout the body, including the lungs, brain, skin, and digestive system. Because they release hormones, NETs can cause a range of symptoms. However, many NETs grow slowly and produce vague symptoms, making them difficult to diagnose early. As a result, a significant number of patients are diagnosed at an advanced stage.
While there is abundant information on more conventional treatments for Neuroendocrine Tumors, our focus here will be on the rationale and available data supporting the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in these specific cases. It is important to emphasize that evidence regarding the benefit of CRS/HIPEC for Neuroendocrine Tumors remains limited. Nevertheless, reports suggest potential benefits for certain patients facing Neuroendocrine Tumors with rare indications for CRS/HIPEC.
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Neuroendocrine tumors (NETs) are a diverse group of tumors that begin in neuroendocrine cells, which are specialized cells that produce hormones. These cells are triggered by neurons to release hormones into the bloodstream. Neuroendocrine cells are found throughout the body, including in the skin, brain, lungs, and gastrointestinal system. As a result, neuroendocrine tumors can develop in any of these areas.[see References: 1] Because these tumors secrete hormones, they often cause a variety of symptoms, leading to a condition known as carcinoid syndrome. However, the lack of distinct symptoms can make diagnosis difficult, resulting in many patients being diagnosed at an advanced stage (estimated to be 20-70% of cases) due to the gradual increase in symptoms as the tumors grow over time.[2-4]
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Neuroendocrine tumors are an area of active research, and both their treatment pathways and classification systems are still evolving. As such, diagnosing and treating these tumors requires a collaborative, multidisciplinary approach. This involves medical oncologists, surgeons, radiologists, and pathologists working together to evaluate results from pathology tests, hormonal tests, and imaging to create an individualized treatment plan. The plan is guided by factors such as the tumor’s location, its pathologic features, and patient-specific factors like age and comorbidities.[5, 6] Treatment options include surgery, somatostatin analogues, chemotherapy, and emerging targeted therapies. Despite new developments, surgery remains a cornerstone treatment for most patients with neuroendocrine tumors, and the majority of these patients will receive surgery.[7]
The extent of surgical resection for neuroendocrine tumors depends on the tumor’s site of origin and size. For early-stage, localized disease, surgery remains the only curative option when no disease is left behind.[2, 8] Surgery also plays a critical role in cases of metastatic disease. Even if the tumor cannot be completely removed, surgery can be performed to alleviate symptoms or significantly reduce the tumor burden, ultimately improving the patient’s quality of life. Several retrospective studies suggest that cytoreductive surgery may also improve survival.[9-11]
The role of cytoreductive surgery (CRS) is well-established, but the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to this procedure remains controversial, with its benefits still uncertain. One study compared outcomes in patients with small bowel neuroendocrine tumors and peritoneal metastases treated with CRS alone or CRS/HIPEC. While the study suggested a potential trend towards improved progression-free survival in the CRS/HIPEC group, the difference was not statistically significant.[12] In contrast, another study found that patients who underwent CRS/HIPEC had a significantly longer disease-free survival (median: 24 months) compared those who received CRS alone (median: 11 months).[13] However, both studies reported more postoperative complications in the CRS/HIPEC group and are focused on only one neuroendocrine tumor type. As a result, there is not enough data to determine whether the survival benefit outweighs the associated risks, though safety outcomes may improve when CRS and/or CRS/HIPEC are performed at specialized centers focused on peritoneal surface malignancies.
Finding Specialized Care
Finding a care provider who is knowledgeable with colorectal cancer and how to treat it is critically important. To search for providers who specialize in performing CRS/HIPEC and providers who specialize in colorectal cancer, navigate to our Find a Specialist page.​​
please note: Our goal is to provide information to help you find a doctor closest to your home that can provide the best quality of care for your diagnosis or your anticipated CRS/HIPEC procedure. The Abdominal Cancers Alliance does not endorse any care provider or medical center over another.
Clinical Trials
There are many actively recruiting clinical trials for neuroendocrine tumors registered online. A full list of all active clinical trials and their current recruitment status can be found on www.ClinicalTrials.gov. Your oncologists (medical, surgical, and radiation) can also help you review clinical trial options and recommendations. There are currently no clinical trials for HIPEC in NETs, probably due to the rarity cancer itself
1. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB. One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008 Jun 20;26(18):3063-72. doi: 10.1200/JCO.2007.15.4377. PMID: 18565894. 2. Boudreaux JP, Klimstra DS, Hassan MM, Woltering EA, Jensen RT, Goldsmith SJ, Nutting C, Bushnell DL, Caplin ME, Yao JC; North American Neuroendocrine Tumor Society (NANETS). The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the Jejunum, Ileum, Appendix, and Cecum. Pancreas. 2010 Aug;39(6):753-66. doi: 10.1097/MPA.0b013e3181ebb2a5. PMID: 20664473. 3. Ter-Minassian M, Chan JA, Hooshmand SM, Brais LK, Daskalova A, Heafield R, Buchanan L, Qian ZR, Fuchs CS, Lin X, Christiani DC, Kulke MH. Clinical presentation, recurrence, and survival in patients with neuroendocrine tumors: results from a prospective institutional database. Endocr Relat Cancer. 2013 Mar 22;20(2):187-96. doi: 10.1530/ERC-12-0340. PMID: 23319495; PMCID: PMC3739696. 4. Hallet J, Law CH, Cukier M, Saskin R, Liu N, Singh S. Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes. Cancer. 2015 Feb 15;121(4):589-97. doi: 10.1002/cncr.29099. Epub 2014 Oct 13. PMID: 25312765. 5. Raphael MJ, Chan DL, Law C, Singh S. Principles of diagnosis and management of neuroendocrine tumours. CMAJ. 2017 Mar 13;189(10):E398-E404. doi: 10.1503/cmaj.160771. PMID: 28385820; PMCID: PMC5359105. 6. Metz DC, Choi J, Strosberg J, Heaney AP, Howden CW, Klimstra D, Yao JC. A rationale for multidisciplinary care in treating neuroendocrine tumours. Curr Opin Endocrinol Diabetes Obes. 2012 Aug;19(4):306-13. doi: 10.1097/MED.0b013e32835570f1. PMID: 22760514. 7. Singh S, Granberg D, Wolin E, Warner R, Sissons M, Kolarova T, Goldstein G, Pavel M, Öberg K, Leyden J. Patient-Reported Burden of a Neuroendocrine Tumor (NET) Diagnosis: Results From the First Global Survey of Patients With NETs. J Glob Oncol. 2016 Jun 8;3(1):43-53. doi: 10.1200/JGO.2015.002980. PMID: 28717741; PMCID: PMC5493232. 8. Strosberg JR, Weber JM, Feldman M, Coppola D, Meredith K, Kvols LK. Prognostic validity of the American Joint Committee on Cancer staging classification for midgut neuroendocrine tumors. J Clin Oncol. 2013 Feb 1;31(4):420-5. doi: 10.1200/JCO.2012.44.5924. Epub 2012 Dec 17. PMID: 23248248. 9. Glazer ES, Tseng JF, Al-Refaie W, Solorzano CC, Liu P, Willborn KA, Abdalla EK, Vauthey JN, Curley SA. Long-term survival after surgical management of neuroendocrine hepatic metastases. HPB (Oxford). 2010 Aug;12(6):427-33. doi: 10.1111/j.1477-2574.2010.00198.x. PMID: 20662794; PMCID: PMC3028584. 10. 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 Jul;197(1):29-37. doi: 10.1016/S1072-7515(03)00230-8. PMID: 12831921. 11. Mayo SC, de Jong MC, Pulitano C, Clary BM, Reddy SK, Gamblin TC, Celinksi SA, Kooby DA, Staley CA, Stokes JB, Chu CK, Ferrero A, Schulick RD, Choti MA, Mentha G, Strub J, Bauer TW, Adams RB, Aldrighetti L, Capussotti L, Pawlik TM. Surgical management of hepatic neuroendocrine tumor metastasis: results from an international multi-institutional analysis. Ann Surg Oncol. 2010 Dec;17(12):3129-36. doi: 10.1245/s10434-010-1154-5. Epub 2010 Jun 29. PMID: 20585879. 12. Hajjar R, Mercier F, Passot G, Pasquer A, Gelli M, Levine EA, Villeneuve L, Poncet G, Walter T, Glehen O. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for small bowel neuroendocrine tumors with peritoneal metastasis. Eur J Surg Oncol. 2022 Jul;48(7):1626-1630. doi: 10.1016/j.ejso.2022.03.019. Epub 2022 Mar 27. PMID: 35418324. 13. Elias D, David A, Sourrouille I, Honoré C, Goéré D, Dumont F, Stoclin A, Baudin E. Neuroendocrine carcinomas: optimal surgery of peritoneal metastases (and associated intra-abdominal metastases). Surgery. 2014 Jan;155(1):5-12. doi: 10.1016/j.surg.2013.05.030. Epub 2013 Sep 29. PMID: 24084595.