Metastatic Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) of Unknown Primary: A Diagnostic Strategy for Localizing the Primary Lesion

Abstract

Background: Localization of primary GEP-NETs is a diagnostic challenge of paramount importance, as resection of the primary lesion may increase treatment efficacy and improve prognosis. Aims: To evaluate the diagnostic value of capsule endoscopy (CE), double balloon enteroscopy (DBE), endoscopic ultrasound (EUS), octreotide scan (OS) and PET-CT for localizing primary GEP-NETs. Methods: Retrospective evaluation of patients with metastatic GEP-NETs and an unknown primary per CT or MRI. These patients had at least one of the 5 diagnostic modalities for localization. Tissue diagnosis was used to confirm the primary lesion. Results: 39 patients with biopsy-proven metastatic GEP-NET were referred to our center for a diagnostic evaluation between July 2002 and September 2010. The mean age was 58, 56% female. We ultimately identified the primary in 30 patients (77%) with various combinations of CE, DBE and EUS. CE was positive in 11/22 patients (50%), 8 of whom were confirmed. DBE was positive in 17/27 procedures (63%) and performed in a total of 22 patients. EUS, usually done after a negative intestinal search, was positive in 11/27 (65%). Octreotide scans were positive in 12/23 patients (52%) with 9 confirmations. 7 patients underwent all 3 endoscopic procedures; 6/7 patients (84%) had the primary localized. Overall, the sensitivities of CE, DBE and EUS were 60% 73% and 77%, respectively (see table). OS, typically considered the gold standard, had a sensitivity of only 59%. PET-CT scans were done on 4 patients and all were negative. Conclusions: CE, DBE, and EUS are highly effective in identifying the primary lesion for patients with metastatic GEP-NETs of unknown primary, especially when all three modalities are utilized. OS is imprecise in localizing lesions and may be less sensitive than any of the 3 endoscopic procedures. The value of PET-CT in the search for the primary lesion remains to be determined. Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of Each Procedure for Detection of Primary Lesions