ABSTRACT
Neuroendocrine neoplasms (NENs) account for 0.5% of all neoplasms worldwide. The aim of the study was to describe the epidemiology of NENs in Italy and the association with a second neoplasm using the Italian Cancer Registries (AIRTUM) database.
Thirty-eight cancer registries were involved in this study in the period 1976-2012. The standardized incidence rates and the relative 5-year survival are reported. Cases by site, sex, and age, and the second cancers associated with patients with NENs are described.
A total of 9,707 NENs were reported to the AIRTUM database: 5,318 males (54.8%) and 4,389 females (45.2%). Lung and small intestine were the most frequent sites in both sexes. The standardized incidence increased from 1 case per 100,000/year
(1976) to 5.46 case per 100,000/year in 2010 (95% CI 4.90-6.06), with a significant difference between rates in males (6.51, 95% CI 5.61-7.51) and in females (4.60, 95 CI 3.91-5.37). Incidence increased gradually in both sexes up to age 40-45, after which it increased rapidly. The 5-year relative survival was 59.7% (53.9% in males and 66.5% in females). NEN patients had a slight, not significant excess risk of having a second tumour: standardized incidence ratio 1.06 (95% CI 0.98-1.15). Of the 9,707 NENs studied, 2,033 (21%) had a second neoplasm: among these, 29 were NENs, 1,360 were other previous tumours, and 644 were other following tumours (78 synchronous and 566 metachronous tumours).
Although traditionally thought to be rare, incidence has increased by nearly sevenfold since 1976. Differences in registration accuracy and classification criteria challenge comparisons between areas and time.

IMPACT STATEMENT
This work highlights how the incidence of neuroendocrine tumors, although rare, is increasing in Italy and the association with second tumors was also evaluated. It can be of support in the choices of clinicians for the management of patients.