Second Primary Malignancies After Appendiceal Neuroendocrine Tumors: A Contemporary SEER-Based Standardized Incidence...

Whether contemporary appendiceal neuroendocrine tumor (NET) survivors have an increased risk of second primary malignancies (SPMs) remains uncertain. We assessed relative incidence and the effect of excluding early post-diagnosis events.

We identified adults aged ≥20 years with malignant appendiceal NETs diagnosed between 2015 and 2023 in Surveillance, Epidemiology, and End Results (SEER) data from 17 registries. Observed and expected SPMs were compared using standardized incidence ratios (SIRs). The primary analysis excluded events occurring within the first two months, with sensitivity analyses using ≥6- and ≥12-month exclusion periods.

The baseline cohort included 4,854 patients. At ≥2 months, 4,522 patients contributed 18,273.65 person-years, with 119 observed SPMs compared with 103.03 expected SPMs (SIR, 1.15; 95% CI, 0.96-1.38). Elevated estimates were observed for malignancies of the digestive system (SIR, 1.56; 95% CI, 1.03-2.27), pancreas (2.51; 1.01-5.17), kidney and renal pelvis (2.36; 1.08-4.49), and thyroid (2.73; 1.36-4.89). Overall SIRs were 1.15, 1.10, and 1.03 across the three exclusion thresholds. Several site-specific estimates decreased, but pancreatic SIRs remained similar (2.51, 2.70, and 2.58). No site-specific confidence interval excluded unity at ≥12 months.

Overall SPM incidence was not significantly elevated. Early site-specific findings warrant caution because of small event counts, multiple comparisons, and possible detection effects that SEER cannot directly measure. Loss of statistical significance with longer exclusion periods does not exclude persistent site-specific excess incidence. These results do not support additional routine organ-directed screening solely based on appendiceal NET history.