Sex Differences in Survival from Neuroendocrine Neoplasia in England 2012–2018: A Retrospective, Population-Based Study

Abstract

Pre-clinical studies have suggested sex hormone signalling pathways may influence tumorigenesis in neuroendocrine neoplasia (NEN). We conducted a retrospective, population-based study to compare overall survival (OS) between males and females with NEN. A total of 14,834 cases of NEN diagnosed between 2012 and 2018, recorded in England’s National Cancer Registry and Analysis Service (NCRAS), were analysed. The primary outcome was OS with 5 years maximum follow-up. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Appendiceal, pulmonary and early-stage NEN were most commonly diagnosed in females; stomach, pancreatic, small intestinal, colonic, rectal and later-stage NEN were more often diagnosed in males. Females displayed increased survival irrespective of the stage, morphology or level of deprivation. On average, they survived 3.62 (95% CI 1.73–5.90) to 10.26 (6.6–14.45) months longer than males; this was statistically significant in NEN of the lung, pancreas, rectum and stomach (p < 0.001). The stage mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. The reasons underlying these differences are not yet understood. Overall, females diagnosed with NEN tend to survive longer than males, and the stage at presentation only partially explains this. Future research, as well as prognostication and treatment, should consider sex as an important factor.

Incidence trend of neuroendocrine tumors and disparities by sex and race/ethnicity in adults from the United States, 2000–2020

“…Previous studies have reported an increase in the incidence rate of overall NET in the USA during the periods of 1973–1999 (Modlin et al ., 2003), 1973–2004 (Yao et al ., 2008), 1993–2004 (Hauso et al ., 2008), 1973–2012 (Dasari et al ., 2017), 2000–2015 (Shen et al ., 2019). Similarly, an increasing trend in other regions, such as England 1995–2018 (White et al ., 2022) and 2012–2018 (White et al ., 2023) were reported. Increased use of imaging techniques or other diagnostic tests, together with the availability of better techniques in cancer screening and diagnosis, were proposed to partly account for such an increase (Chauhan et al ., 2020; Kessel et al ., 2021).…”

Gender-related differences in patients with carcinoid syndrome: new insights from an Italian multicenter cohort study

“…In this light, female gender might represent a risk factor for the occurrence of NEN and related CaS. On the other hand, population-based studies have reported a better overall survival in females compared to males among patients with GEP-NENs [ 16 – 21 ]. In support of these clinical findings, there is an increasing body of evidence from pre-clinical studies providing possible explanations for gender differences in NEN tumorigenesis.…”

“…No gender-based differences in therapeutic approaches was found. Evaluating studies of varying intent (not aimed at evaluating gender differences or focused on CaS), women seemed to have improved outcomes, a slight advantage in response to therapy, especially for liver metastases, and better survival compared to men [ 3 , 18 – 21 , 43 – 46 ]. However, neither our study nor previous analyses revealed any gender-related differences in treatment modalities, response to therapy, and patient outcomes in NEN patients [ 4 , 42 ].…”