Clinically detected gastroenteropancreatic neuroendocrine tumors are on the rise: epidemiological changes in Germany

Abstract

Aim: To study the epidemiologic changes of gastroenteropancreatic neuroendocrine tumors (GEP-NET) in Germany, we analyzed two time periods 1976-1988 and 1998-2006.

Methods: We evaluated epidemiological data of GEP-NET from the former East German National Cancer Registry (DDR Krebsregister, 1976-1988) and its successor, the Joint Cancer Registry (GKR, 1998-2006), which was founded after German reunification. Due to a particularly substantial database the epidemiological data from the federal states of Mecklenburg-Western Pomerania, Saxony, Brandenburg and Thuringia, covering a population of more than 10.8 million people, were analyzed. Survival probabilities were calculated using life table analysis. In addition, GEP-NET patients were evaluated for one or more second (non-GEP-NET) primary malignancies.

Results: A total of 2821 GEP neuroendocrine neoplasms were identified in the two registries. The overall incidence increased significantly between 1976 and 2006 from 0.31 (per 100.000 inhabitants per year) to 2.27 for men and from 0.57 to 2.38 for women. In the later period studied (2004-2006), the small intestine was the most common site. Neuroendocrine (NE) neoplasms of the small intestine showed the largest absolute increase in incidence, while rectal NE neoplasms exhibited the greatest relative increase. Only the incidence of appendiceal NET in women showed little change between 1976 and 2006. Overall survival of patients varied for sex, tumor site and the two periods studied but improved significantly over time. Interestingly, about 20% of the GEP-NET patients developed one or more second malignancies. Their most common location was the gastrointestinal tract. GEP-NET patients without second malignancies fared better than those with one or more of them.

Conclusion: The number of detected GEP-NET increased about 5-fold in Germany between 1976 and 2006. At the same time, their anatomic distribution changed, and the survival of GEP-NET patients improved significantly. Second malignancies are common and influence the overall survival of GEP-NET patients. Thus, GEP-NET warrant our attention as well as intensive research on their tumorigenesis.

Keywords: Endoscopy; Epidemiology; Gastrinoma; German history; Insulinoma; Neuroendocrine; Reunification; Second malignancy; Tumor.

Figure 1

The incidence of gastroenteropancreatic neuroendocrine tumors is shown over time (1976-1988 and 1998-2006). It is presented either as crude incidence or as the number of tumors (per 100.000) age-adjusted to the 1966 world standard population (World standard) or to the 1987 German standard population (German standard). The data shown originate from the former East German National Cancer Registry (DDR Krebsregister) for 1976-1988 or from its successor, the Joint Cancer Registry, for 1998-2006.

Figure 2

Relative changes in the incidence of gastroenteropancreatic neuroendocrine tumor are depicted according to tumor site and sex. A: Changes were calculated for the reference periods 1976-1978 and 2004-2006*; the intervals 1979-1981 and 2004-2006 were chosen for the stomach, since no gastric NE neoplasms were registered in women before 1979; B: Changes in incidence are presented as relative increments age-adjusted to the 1987 German standard population. The data shown originate from the former East German National Cancer Registry (DDR Krebsregister) for the years 1976-1978 or from its successor, the Joint Cancer Registry, for the time period 2004-2006. NE: Neuroendocrine.

Figure 3

Absolute changes in the incidence of gastroenteropancreatic neuroendocrine tumor are shown according to tumor site and sex. A: Changes were calculated for the reference periods 1976-1978 and 2004-2006*; the periods 1979-1981 and 2004-2006 were chosen for the stomach, since no registered gastric NE neoplasms were registered in women before 1979; B: Changes in incidence are presented as absolute increments age-adjusted to the 1987 German standard population. The data shown originate from the former East German National Cancer Registry (DDR Krebsregister) for the years 1976-1978 or from its successor, the Joint Cancer Registry, for the time period 2004-2006. NE: Neuroendocrine.

Figure 4

Overall survival of patients with gastroenteropancreatic neuroendocrine tumor. Two periods of time are compared (1976-1988 and 1998-2006). GEP-NET: Gastroenteropancreatic neuroendocrine tumor.

Figure 5

Second malignancies occurred in 472 of 2821 patients with gastroenteropancreatic neuroendocrine tumor. A: The absolute number; B: The percentage of patients with one or more second (non-gastroenteropancreatic neuroendocrine tumor, non-GEP-NET) neoplasms. 0 = No second neoplasm. GEP-NET: Gastroenteropancreatic neuroendocrine tumor.