Risk of second primary malignancies in survivors of pancreatic neuroendocrine neoplasms from 2000 to 2018

As a result of improved survival, cancer survivors continue to remain at risk of developing second primary malignancies (SPMs). However, the association between first primary pancreatic neuroendocrine neoplasms (PanNENs) and SPMs has not been thoroughly investigated.Using the Surveillance, Epidemiology, and End Results-18 database, patients histologically diagnosed with PanNENs as their first malignancy between 2000 and 2018 were identified. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) and excess absolute risks per 10 000 person-years of SPMs were calculated to estimate the risk of being diagnosed with subsequent cancers compared with the general population.A total of 489 (5.7%) PanNENs survivors developed an SPM during the follow up, with a median latency between first and second cancer diagnoses of 32.0 months. The overall SIR of SPMs was 1.30 (95% CI: 1.19, 1.42) and the excess absolute risk was 35.67 cases per 10 000 person-years in comparison with the general population. Age 25-64 years at PanNENs diagnosis was associated with statistically higher risks for SPMs of all cancers combined. Latency stratification was significant for elevated SPMs risk between 2-23 and 84+ months after diagnosis. White patients were found to have a significantly increased incidence of SPMs (SIR: 1.23, 95% CI: 1.11, 1.35), mainly owing to the higher risk of stomach, small intestine, pancreas, kidney and renal pelvis, and thyroid cancers.Pancreatic neuroendocrine neoplasms survivors experience a significant increase in the burden of SPMs compared with the reference population. The heightened relative risk calls for careful long-term scrutiny as part of survivorship care plans.