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Treatment of advanced disease in patients with well-differentiated neuroendocrine tumors

Nature Reviews Clinical Oncology volume 6, pages 143–152 (2009)Cite this article

Abstract

Well-differentiated neuroendocrine tumors (NETs), which are also referred to as well-differentiated endocrine carcinoma according to WHO terminology, are usually slow-growing cancers, even when they exhibit gross local invasion and/or metastases. The survival of patients with metastatic NET is often measured in years to decades. Once NET progresses or becomes symptomatic the patient's prognosis is poor. An important challenge for clinicians is to distinguish at an early stage those patients who will die with the disease, from those who will succumb because of it, so that the appropriate level of care can be administered. Reliable genomic predictors could provide substantial advancements in prognosis and, possibly, treatment; however, such markers are currently unavailable. Early literature on the treatment of NETs is confounded by a lack of formal objective response criteria. Somatostatin analogs can control symptoms and can stabilize some slow-growing tumors, but rarely result in tumor regression. Surgery is curative in only a minority of patients, and systemic chemotherapy is minimally effective. Advances in the understanding of tumor biology have led to the identification of important cellular processes involved in the pathogenesis of NETs, and agents that target these processes have now entered clinical trials. We will discuss the data on therapies currently used to treat well-differentiated NETs, and the strategies being used in clinical trials.

Key Points

  • Patients with well-differentiated neuroendocrine tumors (NETs), the most common of which are carcinoid tumors and islet-cell carcinomas, typically present with metastatic disease

  • Metastatic disease can be followed expectantly as it is often slow-growing and does not require intervention for many months to years

  • Once the NET progresses or is symptomatic despite somatostatin-analog treatment, therapeutic options are extremely limited and no therapy is currently considered standard

  • Tumor heterogeneity, the varying degree of aggressiveness, and the lack of standard regimens and guidelines for NET treatment pose a substantial clinical challenge

  • Well-differentiated NETs exhibit diverse clinical outcomes, which can sometimes be stratified by certain histopathological features including cytological grade degree, angioinvasion, proliferative index (as assessed by mitotic index and Ki67), tumor size, presence of metastases, and functional activity

  • An understanding of tumor signaling mechanisms has led to the development of promising agents that could target clinically important pathways, but an urgent need remains for genetic markers that identify the clinical phenotypes

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Figure 1: Grading of neuroendocrine tumors (NETs).
Figure 2: Typical presentation of an ileal carcinoid tumor.
Figure 3: A patient with a metastatic nonfunctional carcinoid tumor, Eastern Cooperative Oncology Group performance status 0, with bulky liver disease, which illustrates the tropism of NETs for the liver.

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Authors and Affiliations

  1. DL Reidy is Assistant Attending Physician, LH Tang is Assistant Attending Pathologist and LB Saltz is an Attending Physician, all at the Memorial Sloan–Kettering Cancer Center and Weill Medical College of Cornell University, New York, NY, USA.,

    Diane L Reidy, Laura H Tang & Leonard B Saltz

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  1. Diane L Reidy
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Correspondence to Diane L Reidy.

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Dr Leonard B Saltz has declared he is a consultant and receives grant/research support from Merck and Roche. D Reidy has declared she receives grant/research support from Merck. L Tang has declared no competing interests.

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Reidy, D., Tang, L. & Saltz, L. Treatment of advanced disease in patients with well-differentiated neuroendocrine tumors. Nat Rev Clin Oncol 6, 143–152 (2009). https://doi.org/10.1038/ncponc1326

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