Observation versus Resection for Small Asymptomatic Pancreatic Neuroendocrine Tumors: A Matched Case-Control Study

Eran Sadot, Diane L Reidy-Lagunes, Laura H Tang, Richard Kinh Gian Do, Mithat Gonen, Michael I D'Angelica, Ronald P DeMatteo, T Peter Kingham, Bas Groot Koerkamp, Brian R Untch, Murray F Brennan, William R Jarnagin, Peter J Allen, Eran Sadot, Diane L Reidy-Lagunes, Laura H Tang, Richard Kinh Gian Do, Mithat Gonen, Michael I D'Angelica, Ronald P DeMatteo, T Peter Kingham, Bas Groot Koerkamp, Brian R Untch, Murray F Brennan, William R Jarnagin, Peter J Allen

Abstract

Objective: To analyze the natural history of small asymptomatic pancreatic neuroendocrine tumors (PanNET) and to present a matched comparison between groups who underwent either initial observation or resection. Management approach for small PanNET is uncertain.

Methods: Incidentally discovered, sporadic, small (<3 cm), stage I-II PanNET were analyzed retrospectively between 1993 and 2013. Diagnosis was determined either by pathology or imaging characteristics. Intention-to-treat analysis was applied.

Results: A total of 464 patients were reviewed. Observation was recommended for 104 patients (observation group), and these patients were matched to 77 patients in the resection group based on tumor size at initial imaging. The observation group was significantly older (median 63 vs. 59 years, p = 0.04) and tended towards shorter follow-up (44 vs. 57 months, p = 0.06). Within the observation group, 26 of the 104 patients (25 %) underwent subsequent tumor resection after a median observation interval of 30 months (range 7-135). At the time of last follow-up of the observation group, the median tumor size had not changed (1.2 cm, p = 0.7), and no patient had developed evidence of metastases. Within the resection group, low-grade (G1) pathology was recorded in 72 (95 %) tumors and 5 (6 %) developed a recurrence, which occurred after a median of 5.1 (range 2.9-8.1) years. No patient in either group died from disease. Death from other causes occurred in 11 of 181 (6 %) patients.

Conclusions: In this study, no patient who was initially observed developed metastases or died from disease after a median follow-up of 44 months. Observation for stable, small, incidentally discovered PanNET is reasonable in selected patients.

Conflict of interest statement

DISCLOSURE All authors declare that they have no conflict of interest regarding this study.

Figures

FIG. 1
FIG. 1
Distribution of tumor size over time in any patient whose PanNET was resected at MSKCC during the last two decades (n = 377). Yellow line represents the tumor size and blue line represents the number of patients
FIG. 2
FIG. 2
Stage I–II PanNET management strategies during the study period (1993–2013) by intention-to-treat analysis* (n = 455). *Excluding nine patients with familial syndromes who were not operated
FIG. 3
FIG. 3
Study design flow chart. Overall 464 stage I–II PanNET patients were identified. After applying the exclusion criteria, the observation group (n = 104) was identified, and then a resection group (n = 77) was matched
FIG. 4
FIG. 4
Change in tumor size over time in the observation group (n = 104, each dot/diamond represents a single patient). Fifty-three (51 %) patients experienced increase in tumor size, 19 (18 %) patients experienced no change in tumor size, and 32 (31 %) patients experienced decrease in tumor size
FIG. 5
FIG. 5
Overall survival and metastasis-free survival Kaplan–Meier estimates stratified by management strategy (log-rank test)

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