Second Primary Malignancies in Patients with a Neuroendocrine Neoplasm in England.

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.

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

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.

Primary renal neuroendocrine neoplasms: A systematic literature review, report of four local cases, and original survival analysis of 63 patients from a national registry 2012-2018.

Primary renal neuroendocrine neoplasms (NEN) are rare. We aimed to conduct a systematic review, present local cases, and analyse data from the England's National Cancer Registration and Analysis Service (NCRAS) to provide comprehensive evidence on clinical experience, incidence, and survival to better characterize these tumours. First, a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method; second, a synthesis of local cases; and, finally, a retrospective population-based cohort analysis of renal NEN recorded between 2012 and 2018 on NCRAS were performed. Kaplan-Meier estimator was used to calculate overall survival and Cox proportional hazard regression to identify prognostic factors. Systematic review identified 48 articles and the evidence was summarized and presented. We reported data from four local cases presenting with abdominal and back pain but without carcinoid syndrome. In population-based analysis, we identified 63 cases of renal NEN between 2012 and 2018 from the registry. Age-standardized incidence was 0.09-0.32 per million with a median age of 64 years (interquartile range = 48-72 years). Survival was worse in males and those aged 64 years and over. Five-year survival for renal neuroendocrine tumours (NET) was 69.8% (95% confidence interval = 66.6-72.7) and neuroendocrine carcinomas (NEC) was 38.4% (95% confidence interval = 34.6-42.0). No independent predictive factor was identified in the multivariable analyses. We have given a systematic review of evidence, published local experience, and reported incidence and survival of renal NEN in England for the first time. We have provided clinicians with evidence on diagnosis and proposed a treatment algorithm of theses rare tumours. The incidence and median age of presentation in England is similar to other published series. Renal NET has better survival than renal NEC as expected. A uniform classification system would reduce inconsistencies in reporting and standardize treatment decisions for this neoplasia.

Incidence and survival of neuroendocrine neoplasia in England 1995-2018: A retrospective, population-based study.

Background: Neuroendocrine neoplasia (NEN) incidence is rising internationally. We aimed to evaluate the epidemiology of NEN in England and examine changes in survival over time. Methods: 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. Findings: 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. Interpretation: 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. Funding: Data were extracted and transferred using a grant from Neuroendocrine cancer UK.

Goblet Cell Adenocarcinoma of the Appendix: A Systematic Review and Incidence and Survival of 1,225 Cases From an English Cancer Registry.

Background: Goblet cell adenocarcinoma (GCA) of the appendix is a rare and aggressive tumour with varying nomenclature and classification systems. This has led to heterogeneity in published data, and there is a lack of consensus on incidence, survival, and management. Methods: We provide an overview of GCA with a comprehensive systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and a retrospective analysis of all cases recorded in the English National Cancer Registration and Analysis Service database between 1995 and 2018. The Kaplan-Meier estimator was used to calculate overall survival, and Cox proportional hazards regression was used to identify prognostic factors. Results: The systematic review demonstrated an incidence of 0.05-0.3 per 100,000 per year among North American registry studies. The 1-, 3-, and 5-year survival rate was 95.5%, 85.9%-87.6%, and 76.0%-80.6%, respectively. Age, stage, and grade were identified as prognostic factors for survival. Our analysis included 1,225 cases. Age-standardised incidence was 0.0335 per year in 1995 and gradually rose to 0.158 per year in 2018. The 1-, 3-, and 5-year survival rate was 90.0% [95% confidence interval (95% CI): 85.4-94.0], 76.0% (95% CI: 73.8-80.9), and 68.6% (95% CI: 65.9-72.2), respectively. On univariate Cox regression analyses, female sex, stage, and grade were associated with worse overall survival. On multivariate analysis, only stage remained a statistically significant prognostic factor. Conclusions: GCA of the appendix is rare, but incidence is increasing. We report a lower incidence and survival than North American registry studies. Higher stage was associated with decreased survival. Further prospective studies are required to establish optimal management.