Neuroendocrine neoplasia (NEN) incidence is rising internationally. We aimed to evaluate the epidemiology of NEN in England and examine changes in survival over time. A retrospective, population-based study using nationally representative data between 1995 and 2018 from the National Cancer Registry and Analysis Service (NCRAS) in England was conducted on 63,949 tumours. Age-standardized incidence was calculated using Office for National Statistics (ONS) data. Overall survival (OS) was calculated using the Kaplan-Meier estimator. Multivariable analysis was performed using an accelerated failure time model. Of 63,949 cases, 50.5% (32,309) were female. Age-adjusted incidence increased 3.7-fold between 1995 and 2018 from 2.35 to 8.61 per 100,000. In 2018, highest incidence occurred in lung (1.47 per 100,000), small intestine (1.46 per 100,000), pancreas (1.00 per 100,000) and appendix (0.95 per 100,000). In multivariable analysis, age, sex, morphology, stage, site and deprivation were independent predictors of survival (p < 0.001). Survival of the entire cohort, and by primary site, is improving over time. NEN incidence continues to rise in England with survival improving over time. Relatively high survival compared to other cancers is an issue for long-term outcomes and funding of care. Data were extracted and transferred using a grant from Neuroendocrine cancer UK.

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.

Introduction: Patients with neuroendocrine neoplasms (NENs) may often develop other malignancies. This study aimed to identify the frequency at which these second malignancies occurred in England. Methods: Data were extracted from the National Cancer Registration and Analysis Service (NCRAS) on all patients diagnosed with a NEN at one of eight NEN site groups between 2012 and 2018: appendix, caecum, colon, lung, pancreas, rectum, small intestine, and stomach. WHO International Classification of Disease Edition-10 (ICD-10) codes were used to identify patients who had been diagnosed with an additional non-NEN cancer. Standardized incidence ratios (SIRs) for tumours diagnosed after the index NEN were produced for each non-NEN cancer type by sex and site. Results: A total of 20,579 patients were included in the study. The most commonly occurring non-NEN cancers after NEN diagnosis were the prostate (20%), lung (20%), and breast (15%). Statistically significant SIRs were observed for non-NEN cancer of the lung (SIR = 1.85, 95% CI: 1.55–2.22), colon (SIR = 1.78, 95% CI: 1.40–2.27), prostate (SIR = 1.56, 95% CI: 1.31–1.86), kidney (SIR = 3.53, 95% CI: 2.72–4.59), and thyroid (SIR = 6.31, 95% CI: 4.26–9.33). When stratified by sex, statistically significant SIRs remained for the lung, renal, colon, and thyroid tumours. Additionally, females had a statistically significant SIR for stomach cancer (2.65, 95% CI: 1.26–5.57) and bladder cancer (SIR = 2.61, 95% CI: 1.36–5.02). Conclusion: This study found that patients with a NEN experienced a metachronous tumour of the lung, prostate, kidney, colon, and thyroid at a higher rate than the general population of England. Surveillance and engagement in existing screening programmes are required to enable earlier diagnosis of second non-NEN tumours in these patients.

Background: For decades, the incidence of neuroendocrine tumours (NETs) has been steadily increasing. Existing research suggests that patient sociodemographic characteristics, such as sex and deprivation, may play a role in who survives a NET diagnosis. This systematic review identifies the available evidence assessing the impact of sex and deprivation on the prognosis of patients diagnosed with NETs. Methods: Using protocol-driven search terms, Embase and Ovid were searched in July 2024 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The identified studies were critically appraised using the Joanna Briggs Manual for Evidence Synthesis. Results: The search identified 2041 unique citations of which 66 articles were subsequently included. One study was excluded based on the critical appraisal. Findings were reported by geographical location. Included studies indicate a female survival advantage in North America and England, but the impact of sex on NET prognosis in wider European and Asian countries is less clear. The impact of deprivation on NET prognosis was assessed in North America, with one study conducted in Europe. Conclusions: Significant data heterogeneity across studies posed challenges for comparability between studies and hindered statistical analyses of these data. In North America and England, females diagnosed with NETs tend to survive longer than males. Existing single-centre studies do not provide conclusive evidence on the impact of sex on NET survival in Asian countries, and . While a greater number of population-based studies within Europe and Asia are needed., Ffuture research should also focus on addressing outcome heterogeneity across NET research to allow for more robust evidence synthesis, providing increased accuracy and generalisability of study results.

Objective: The time from onset of symptoms of neuroendocrine neoplasia (NEN) to diagnosis ranges between 5 and 7 years. Risk factors associated with this and the difference in overall survival (OS) between routine and emergency presentation (RP and EP) are not known. Design: A retrospective, population-based study. Methods: A retrospective, population-based study of gastroenteropancreatic and lung NEN registered on England’s national cancer between 2012 and 2021. Factors associated with worse OS, or emergency or late presentation (EP or LP), were evaluated using the Kaplan–Meier estimator, Cox and logistic regressions, and machine learning (ML) in two models. Results: A total of 21,345 NEN were included. 20.3% were EP. EP showed worse OS compared to RP. Factors associated with EP were male sex, advanced stage, worse deprivation and NEC. The ML model showed EP related to advanced stage, small intestinal NEN, NEC, advanced age, deprivation and male sex in decreasing order of importance. Factors associated with LP included EP, male sex and NEC. The ML model showed that NEC, small intestinal NEN, advanced age, EP and male sex are associated with LP in decreasing order of importance. Conclusion: EP is associated with poor survival. Addressing the associated factors may aid in timely diagnosis and improved survival.