Monitoring Carcinoid Tumors and Pancreatic Neuroendocrine Tumors

Monitoring

Monitoring patients with carcinoid tumors and pancreatic neuroendocrine tumors (PNET) is recommended in order to assess whether there is progression of disease.1,2 Optimal monitoring of patients requires a multidisciplinary approach with nurses, primary care practitioners, gastroenterologists, oncologists (medical, surgical, and radiation), radiologists, endocrinologists, nuclear medicine physicians, molecular geneticists, clinical immunologists, pathologists, and surgeons involved in the follow-up process.1,3

The National Comprehensive Cancer Network (NCCN) recommends that all patients with carcinoid tumors be re-evaluated 3 to 12 months postresection, and every 6 to 12 months thereafter with history and physical examination and imaging as clinically indicated.1 It is recommended that patients with midgut carcinoid tumors be reassessed once between 3 and 6 months after complete resection.2 Subsequently, patients with midgut carcinoid tumors should be assessed every 6 to 12 months for at least 7 years.2

General surveillance for carcinoid tumors and PNET should include a history and physical examination, measurement of urinary 5-hydroxyindoleacetic acid (5-HIAA) and serum chromogranin A (CgA), abdominal/pelvic triple-phase contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), and/or SRS scans and measurement of biochemical markers.2 Surveillance may vary according to treatment setting (Table 8).

Table 8. Surveillance by Treatment Setting: Postresection, Recurrent, Unresectable, Localized and Metastatic Disease1
Postresection Recurrent disease Unresectable disease Localized disease Metastatic disease
  • History and physical examination
  • Imaging as clinically indicated1
  1. – CT scan or MRI
  • Biomarkers
  1. – 5-HIAA
  2. – CgA
  • History and physical examination
  • Imaging as clinically indicated
  • Multiphasic CT scan or MRI
  • Biomarkers from preoperative evaluation
  • History and physical examination
  • Imaging as clinically indicated
  • CT scan or MRI
  • Echocardiogram for patients with carcinoid syndrome
  • Biomarkers
  1. – 5-HIAA
  2. – CgA
  • 3 to 12 months postresection
  1. – Examination
  2. – Biomarkers
  3. – Imaging (CT/MRI)
  • Year 1 to 3
  1. – Examination and biomarkers every 6 months
  • ≥Year 4
  1. – Examination and biomarkers annually
  2. – Imaging studies as clinically indicated
  • Biomarkers and imaging every 3 to 6 months
  • Echocardiogram for patients with carcinoid syndrome

Prognosis

Prognostic indicators allow physicians to monitor disease progression.4 Table 9 lists both positive and negative prognostic indicators (Table 9).

Table 9. Prognostic Indicators4-6
Positive Indicators Negative Indicators
Age <50 years5 Hepatic metastases5
Female gender5 Atypical histological features5
Low grade6 Presence of carcinoid syndrome5
Tumor size <3 cm5 Distant metastases6
Well differentiated6 Presence of second malignancy5
Low levels of CgA5 High levels of pancreastatin4
Low levels of neurokinin A4 Depth of invasion5

The development or presence of a second malignancy such as an adenocarcinoma is associated with a worse prognosis, as is the occurence of carcinoid syndrome.5 High levels of pancreastatin confer a poor prognosis due to active progressive liver disease.4

For patients with NET and distant metastases, the 5-year survival rates are 35% for well-differentiated/moderately differentiated and 4% for poorly differentiated/anaplastic carcinoid tumors.6

It is important to note here that patients presenting with relatively small primary tumors can have metastatic potential.7

Survival can also be affected by the presence of symptomatic carcinoid heart disease (4.4 year median survival), skeletal metastases (3-year median survival from diagnosis of bone lesions),8 and high CgA levels (5-year median survival: 22% compared with 63% for low CgA levels).9 Low levels of neurokinin A increase survival in patients with midgut carcinoid tumors.4

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References
  1. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: neuroendocrine tumors. https://www.nccn.org/professionals/physician_gls/PDF/neuroendocrine.pdf. Accessed June 27, 2016.
  2. Boudreaux JP, Klimstra DS, Hassan MM et al. 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;39:753-766.
  3. Kaltsas GA, Besser GM, Grossman AB. The diagnosis and medical management of advanced neuroendocrine tumors. Endocr Rev. 2004;25:458-511.
  4. Ardill JE, O'Dorisio TM. Circulating biomarkers in neuroendocrine tumors of the enteropancreatic tract: application to diagnosis, monitoring disease, and as prognostic indicators. Endocrinol Metab Clin North Am. 2010;39:777-790.
  5. Jensen RT, Doherty GM. Section 6. Carcinoid tumors and the carcinoid syndrome (Chapter 34.6 Cancer of the Endocrine System) In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. CancerPrinciples and Practice of Oncology. 7th ed. New York, NY: Lipppincott, Williams & Wilkins; 2005;1813-1833.
  6. Yao JC, Hassan M, Phan A et al. 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;26:3063-3072.
  7. Modlin IM, Oberg K, Chung DC et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9:61-72.
  8. Strosberg J, Gardner N, Kvols L. Survival and prognostic factor analysis of 146 metastatic neuroendocrine tumors of the midgut. Neuroendocrinology. 2009;89:471-476.
  9. Ardill JES, Erikkson B. The importance of the measurement of circulating markers in patients with neuroendocrine tumours of the pancreas and gut. Endocrine-Related Cancer. 2003;10: 459-462.