Incidence and survival of soft tissue sarcoma in England between 2013 and 2017, an analysis from the National Cancer Registration and Analysis Service.

There is a paucity of population-based data detailing the incidence and survival of patients with soft tissue sarcoma (STS), in part due to the heterogeneity of disease and changes to classification. Here, the incidence and survival of all STS subtypes registered in England between 2013 and 2017 were analysed using cancer registry data held by the National Cancer Registration and Analysis Service. Age-standardised incidence rates were calculated per 1 000 000 using the 2013 European Standard Population. Net survival was computed using Brenner's alternative method, with the Ederer II estimator. Age-specific overall survival was assessed using Kaplan-Meier. The influence of age, sex, socioeconomic deprivation and diagnostic routes on survival was assessed using Cox proportional hazards modelling. In total, 19 717 patients were diagnosed with STS, an average of 3943 patients per year and representing approximately 0.8% of malignancies. The most common histological diagnoses were Gastrointestinal Stromal Tumours (GIST), leiomyosarcoma and undifferentiated sarcoma, accounting for 20.2%, 13.3% and 12.7% of all sarcomas, respectively. Five-year net survival for all malignant STS was 65.0%; and was lowest for patients with vascular tumours at 39%. Patients from most deprived cohorts had 23% greater chance of dying within 5 years than patients in least deprived areas. This population-based study has allowed us for the first time to define the incidence and survival rates of prevalent STS subtypes in England such as GIST, liposarcoma and leiomyosarcoma, as well as rare entities and groups with inferior outcome. This data is invaluable for service provision, benchmarking and addressing inequality.

'Get Data Out' Skin: national cancer registry incidence and survival rates for all registered skin tumour groups for 2013-2019 in England.

BACKGROUND: Providing detailed skin cancer statistics, including incidence and survival, by tumour type and patient characteristics is important for up-to-date epidemiological information. OBJECTIVES: To create a new clinically relevant consensus-based classification for registered skin tumours using tumour type and patient characteristics and to describe its application to all registered tumours in England between 2013 and 2019. METHODS: Tumours with skin topographical codes (ICD-10) and morphology and behaviour (ICD-O3) were grouped together in an iterative process creating a hierarchical tree structure. The primary-level grouping partitioned skin tumours into skin cancer, melanoma in situ, extramammary Paget disease (EMPD) and tumours of uncertain malignant potential. Second-level groups split skin cancer into keratinocyte cancer (KC), melanoma and rare cancers. The third-level group split KC into basal cell carcinoma (BCC) and squamous cell carcinoma (cSCC). Further groups were split into genital or non-genital, first or subsequent tumour, age, gender, stage, or National Health Service (NHS) region. Incidence counts, Kaplan-Meier and net survival estimates and referral routes [two-week wait (TWW), general practitioner (GP), outpatient] categorisations were calculated for each grouping across all years. RESULTS: A total of 1 445 377 skin cancers and 49 123 precancerous lesions and undefined entities were registered in England between 2013 and 2019. Skin tumours and skin cancer incidence rates are increasing for most tumour types. The most common type of skin cancer was BCC with an incidence rate of 282.36 per 100 000 person-years (PYs) [n = 158 934, 95% confidence interval (CI) 280.98-283.76] in 2019, followed by cSCC with an incidence rate of 85.24 per 100 000 PYs (n = 47 977, 95% CI 84.48-86.00) and melanoma with 27.24 (n = 15 332, 95% CI 26.81-27.67) per 100 000 PYs. Each year approximately 1800 rare skin cancers, 1500 genital cSCCs and 100 cases of EMPD are registered. Of 15 000 melanoma cases, 120 cases of melanoma occur in individuals aged < 25 years annually. One-year and five-year overall net survival varies by tumour type. cSCC 5-year net survival (89.8%, 95% CI 88.8-90.9) was comparable to the net survival of all melanomas (89.6%, 95% CI 88.7-90.6). BCC had excellent survival (overall net survival > 100%). Patients with late-stage melanoma, Merkel cell carcinoma and genital cSCC have a 5-year net survival < 60%. Older patients received fewer TWW referrals than their younger counterparts with the same tumour type at the same location. Patients with acral lentiginous melanoma had fewer TWW referrals and more standard GP referrals than patients with common melanomas. CONCLUSIONS: 'Get Data Out' Skin provides detailed and up-to-date statistics on all registrable skin tumours in England, including for the first time precancerous lesions and rare subtypes of common cancers. These data can be used by clinicians, researchers and commissioners to better understand skin cancer and improve resource allocation.

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.

Sebaceous carcinoma epidemiology, associated malignancies and Lynch/Muir-Torre syndrome screening in England from 2008 to 2018.

BACKGROUND: Sebaceous carcinomas (SC) may be associated with the cancer predisposition syndrome Muir-Torre/Lynch syndrome (MTS/LS), identifiable by SC mismatch repair (MMR) screening; however, there is limited data on MMR status of SC. OBJECTIVE: To describe the epidemiology of SC, copresentation of other cancers, and population level frequency of MMR screening in SC. METHODS: A population-based retrospective cohort study of SC patients in the National Cancer Registration and Analysis Service in England. RESULTS: This study included 1077 SC cases (739 extraocular, 338 periocular). Age-standardized incidence rates (ASIR) were higher in men compared with women, 2.74 (95% CI, 2.52-9.69) per 1,000,000 person-years for men versus 1.47 person-years (95% CI, 1.4-1.62) for women. Of the patients, 19% (210/1077) developed at least one MTS/LS-associated malignancy. MMR immunohistochemical screening was performed in only 20% (220/1077) of SC tumors; of these, 32% (70/219) of tumors were MMR deficient. LIMITATIONS: Retrospective design. CONCLUSIONS: Incorporation of MMR screening into clinical practice guidelines for the management of SC will increase the opportunity for MTS/LS diagnoses, with implications for cancer surveillance, chemoprevention with aspirin, and immunotherapy treatment targeted to MTS/LS cancers.

Incidence, prevalence and survival in patients with Langerhans cell histiocytosis: A national registry study from England, 2013-2019.

This analysis is the largest population-based study to date to provide contemporary and comprehensive epidemiological estimates of all third edition of the International Classification of Diseases for Oncology (ICD-O-3) coded Langerhans cell histiocytosis (LCH) from England. People of all ages were identified from the National Cancer Registration Dataset using ICD-O-3 morphologies 9751-9754 for neoplasms diagnosed in 2013-2019. A total of 658 patients were identified, of whom 324 (49%) were children aged <15 years. The age-standardised incidence rate was 4.46 (95% confidence interval [CI] 3.99-4.98) per million children and 1.06 (95% CI 0.94-1.18) per million adults aged ≥15 years. Prevalence of LCH was 9.95 (95% CI 9.14-10.81) per million persons at the end of 2019. The 1-year overall survival (OS) was 99% (95% CI 97%-100%) for children and 90% (95% CI 87%-93%) for adults. Those aged ≥60 years had poorer OS than those aged <15 years (hazard ratio [HR] 22.12, 95% CI 7.10-68.94; p < 0.001). People in deprived areas had lower OS than those in the least deprived areas (HR 5.36, 95% CI 1.16-24.87; p = 0.03). There will inevitably be other environmental factors and associations yet to be identified, and the continued standardised data collection will allow further evaluation of data over time. This will be increasingly important with developments in LCH management following the large collaborative international trials such as LCH IV.

Validation of four cutaneous squamous cell carcinoma staging systems using nationwide data.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer worldwide with relatively low metastatic potential (2-5%). Developments in therapeutic options have highlighted the need to better identify high-risk patients who could benefit from closer surveillance, adjuvant therapies and baseline/follow-up imaging, while at the same time safely omitting low-risk patients from further follow-up. Controversy remains regarding the predictive performance of current cSCC staging systems and which methodology to adopt. OBJECTIVES: To validate the performance of four cSCC staging systems [American Joint Committee on Cancer 8th edition (AJCC8), Brigham and Women's Hospital (BWH), Tübingen and Salamanca T3 refinement] in predicting metastasis using a nationwide cohort. METHODS: A nested case-control study using data from the National Disease Registration Service, England, 2013-2015 was conducted. Metastatic cSCC cases were identified using an algorithm to identify all potential cases for manual review. These were 1 : 1 matched on follow-up time to nonmetastatic controls randomly selected from 2013. Staging systems were analysed for distinctiveness, homogeneity, monotonicity, specificity, positive predictive value (PPV), negative predictive value (NPV) and c-index. RESULTS: We included 887 metastatic cSCC cases and 887 nonmetastatic cSCC controls. The BWH system showed the highest specificity [92.8%, 95% confidence interval (CI) 90.8-94.3%, PPV (13.2%, 95% CI 10.6-16.2) and c-index (0.84, 95% CI 0.82-0.86). The AJCC8 showed superior NPV (99.2%, 95% CI 99.2-99.3), homogeneity and monotonicity compared with the BWH and Tübingen diameter and thickness classifications (P < 0.001). Salamanca refinement did not show any improvement in AJCC8 T3 cSCC staging. CONCLUSIONS: We validated four cSCC staging systems using the largest nationwide dataset of metastatic cSCC so far. Although the BWH system showed the highest overall discriminative ability, PPV was low for all staging systems, which shows the need for further improvement and refining of current cSCC staging systems.

Immunohistochemistry and Next-generation Sequencing Are Complementary Tests in Identifying PTEN Abnormality in Endometrial Carcinoma Biopsies.

PTEN plays a central role in the pathogenesis of endometrial carcinoma. Previous studies reported a high interobserver reproducibility for the interpretation of PTEN immunohistochemistry (IHC). However, PTEN IHC and its interpretation remain challenging during laboratory practice. The purpose of this study was to reevaluate PTEN IHC pattern in direct comparison to next-generation sequencing in identifying PTEN abnormality. IHC and tagged-amplicon next-generation sequencing PTEN sequencing was performed on 182 endometrial carcinoma biopsy/curetting samples from five centers (Barts, Calgary, Cambridge, Leiden, and Vancouver). Sensitivity, specificity and accuracy of PTEN IHC to predict loss of function PTEN mutations were calculated. Abnormalities of PTEN in association with histotype and molecular subtype were assessed. A total of 5 PTEN IHC patterns were recorded: absent, subclonal loss, equivocal, reduced (relative to internal control) and retained. The absence of PTEN IHC has a sensitivity of 75.4% (95% confidence interval: 62.7-85.5%), a specificity of 84.6% (95% confidence interval: 76.2%-90.9%), and accuracy of 81.2% (95% confidence interval: 74.4%-86.9%) in predicting loss of function PTEN mutation. PTEN abnormality by complementary interpretation of both assays was present in 91.9% of endometrial endometrioid carcinoma, grade 1, and significantly higher in endometrial endometrioid carcinomas of all grades compared with endometrial serous carcinoma (80.0% vs. 19.4%, P<0.0001). PTEN abnormalities are common across all molecular subtypes of endometrioid carcinomas. Our data support the use of ancillary PTEN IHC for diagnostic purposes in endometrial neoplasms. However, for clinical trial design complementary testing of both IHC and sequencing of PTEN should be considered to assess the PTEN status in endometrial carcinomas.

Risk factors for metastatic cutaneous squamous cell carcinoma: Refinement and replication based on 2 nationwide nested case-control studies.

BACKGROUND: Risk factors for cutaneous squamous cell carcinoma (cSCC) metastasis have been investigated only in relatively small data sets. OBJECTIVE: To analyze and replicate risk factors for metastatic cSCC. METHODS: From English and Dutch nationwide cancer registry cohorts, metastatic cases were selected and 1:1 matched to controls. The variables were extracted from pathology reports from the National Disease Registration Service in England. In the Netherlands, histopathologic slides from the Dutch Pathology Registry were revised by a dermatopathologist. Model building was performed in the English data set using backward conditional logistic regression, whereas replication was performed using the Dutch data set. RESULTS: In addition to diameter and thickness, the following variables were significant risk factors for metastatic cSCC in the English data set (n = 1774): poor differentiation (odds ratio [OR], 4.56; 95% CI, 2.99-6.94), invasion in (OR, 1.69; 95% CI, 1.05-2.71)/beyond (OR, 4.43; 95% CI, 1.98-9.90) subcutaneous fat, male sex (OR, 2.59; 95% CI, 1.70-3.96), perineural/lymphovascular invasion (OR, 2.12; 95% CI, 1.21-3.71), and facial localization (OR, 1.57; 95% CI, 1.02-2.41). Diameter and thickness showed significant nonlinear relationships with metastasis. Similar ORs were observed in the Dutch data set (n = 434 cSCCs). LIMITATIONS: Retrospective use of pathology reports in the English data set. CONCLUSION: cSCC staging systems can be improved by including differentiation, clinical characteristics such as sex and tumor location, and nonlinear relationships for diameter and thickness.

The International Collaboration for Cancer Classification and Research.

Gaps in the translation of research findings to clinical management have been recognized for decades. They exist for the diagnosis as well as the management of cancer. The international standards for cancer diagnosis are contained within the World Health Organization (WHO) Classification of Tumours, published by the International Agency for Research on Cancer (IARC) and known worldwide as the WHO Blue Books. In addition to their relevance to individual patients, these volumes provide a valuable contribution to cancer research and surveillance, fulfilling an important role in scientific evidence synthesis and international standard setting. However, the multidimensional nature of cancer classification, the way in which the WHO Classification of Tumours is constructed, and the scientific information overload in the field pose important challenges for the translation of research findings to tumour classification and hence cancer diagnosis. To help address these challenges, we have established the International Collaboration for Cancer Classification and Research (IC3 R) to provide a forum for the coordination of efforts in evidence generation, standard setting and best practice recommendations in the field of tumour classification. The first IC3 R meeting, held in Lyon, France, in February 2019, gathered representatives of major institutions involved in tumour classification and related fields to identify and discuss translational challenges in data comparability, standard setting, quality management, evidence evaluation and copyright, as well as to develop a collaborative plan for addressing these challenges.

p53 immunohistochemistry is an accurate surrogate for TP53 mutational analysis in endometrial carcinoma biopsies.

TP53 mutations are considered a surrogate biomarker of the serous-like 'copy number high' molecular subtype of endometrial carcinoma (EC). In ovarian carcinoma, p53 immunohistochemistry (IHC) accurately reflects mutational status with almost 100% specificity but its performance in EC has not been established. This study tested whether p53 IHC reliably predicts TP53 mutations identified by next-generation sequencing (NGS) in EC biopsy samples for all ECs and as part of a molecular classification algorithm after exclusion of cases harbouring mismatch repair defects (MMRd) or pathogenic DNA polymerase epsilon exonuclease domain mutations (POLEmut). A secondary aim assessed inter-laboratory variability in p53 IHC. From a total of 207 cases from five centres (37-49 cases per centre), p53 IHC carried out at a central reference laboratory was compared with local IHC (n = 164) and curated tagged-amplicon NGS TP53 sequencing results (n = 177). Following consensus review, local and central p53 IHC results were concordant in 156/164 (95.1%) tumours. Discordant results were attributable to both interpretive and technical differences in staining between the local and central laboratories. When results were considered as any mutant pattern versus wild-type pattern staining, however, there was disagreement between local and central review in only one case. The concordance between p53 IHC and TP53 mutation was 155/168 (92.3%) overall, and 117/123 (95.1%) after excluding MMRd and POLEmut EC. Three (3/6) discordant results were in serous carcinomas with complete absence of p53 staining but no detectable TP53 mutation. Subclonal mutant p53 IHC expression was observed in 9/177 (5.1%) cases, of which four were either MMRd or POLEmut. Mutant pattern p53 IHC was observed in 63/63 (100%) serous carcinomas that were MMR-proficient/POLE exonuclease domain wild-type. Optimised p53 IHC performs well as a surrogate test for TP53 mutation in EC biopsies, demonstrates excellent inter-laboratory reproducibility, and has high clinical utility for molecular classification algorithms in EC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The diagnostic performance of CA125 for the detection of ovarian and non-ovarian cancer in primary care: A population-based cohort study.

BACKGROUND: The serum biomarker cancer antigen 125 (CA125) is widely used as an investigation for possible ovarian cancer in symptomatic women presenting to primary care. However, its diagnostic performance in this setting is unknown. We evaluated the performance of CA125 in primary care for the detection of ovarian and non-ovarian cancers. METHODS AND FINDINGS: We studied women in the United Kingdom Clinical Practice Research Datalink with a CA125 test performed between 1 May 2011-31 December 2014. Ovarian and non-ovarian cancers diagnosed in the year following CA125 testing were identified from the cancer registry. Women were categorized by age: <50 years and ≥50 years. Conventional measures of test diagnostic accuracy, including sensitivity, specificity, and positive predictive value, were calculated for the standard CA125 cut-off (≥35 U/ml). The probability of a woman having cancer at each CA125 level between 1-1,000 U/ml was estimated using logistic regression. Cancer probability was also estimated on the basis of CA125 level and age in years using logistic regression. We identified CA125 levels equating to a 3% estimated cancer probability: the "risk threshold" at which the UK National Institute for Health and Care Excellence advocates urgent specialist cancer investigation. A total of 50,780 women underwent CA125 testing; 456 (0.9%) were diagnosed with ovarian cancer and 1,321 (2.6%) with non-ovarian cancer. Of women with a CA125 level ≥35 U/ml, 3.4% aged <50 years and 15.2% aged ≥50 years had ovarian cancer. Of women with a CA125 level ≥35 U/ml who were aged ≥50 years and who did not have ovarian cancer, 20.4% were diagnosed with a non-ovarian cancer. A CA125 value of 53 U/ml equated to a 3% probability of ovarian cancer overall. This varied by age, with a value of 104 U/ml in 40-year-old women and 32 U/ml in 70-year-old women equating to a 3% probability. The main limitations of our study were that we were unable to determine why CA125 tests were performed and that our findings are based solely on UK primary care data, so caution is need in extrapolating them to other healthcare settings. CONCLUSIONS: CA125 is a useful test for ovarian cancer detection in primary care, particularly in women ≥50 years old. Clinicians should also consider non-ovarian cancers in women with high CA125 levels, especially if ovarian cancer has been excluded, in order to prevent diagnostic delay. Our results enable clinicians and patients to determine the estimated probability of ovarian cancer and all cancers at any CA125 level and age, which can be used to guide individual decisions on the need for further investigation or referral.

Pancreatic cancer incidence and survival and the role of specialist centres in resection rates in England, 2000 to 2014: A population-based study.

BACKGROUND: The aim was to compare population-based survival for exocrine pancreatic cancer in England in the 23 regions covered by specialist centres. The centres were initiated in 2001, covering populations of 2-4 million. METHODS: We examined incidence for adults diagnosed with a pancreatic exocrine cancer during 1995-2014 and age-standardised net survival up to five years after diagnosis for patients diagnosed during 2000-2013. We examined variation in regional resection rates and survival for patients diagnosed during 2010-2013. The data were extracted from the National Cancer Registration and Analysis Service. RESULTS: Age-standardised annual incidence rates of exocrine pancreatic cancer increased from 17.1 per 100,000 during 1995-1999 to 18.7 during 2010-2014. Age-standardised one-year and five-year net survival increased from 17.9% and 3.6%, respectively, for 2000-2009, to 21.6% and 4.2% during 2010-2013. There were 2086 (8.9%) resections among 23,415 patients diagnosed with an exocrine tumour in 2010-2013. The proportion ranged from 5.1% to 19.6% between centres. Among resected patients, survival was 73.0% at one year and 20.2% at five years. Of the total 2118 resected patients, 18 (0.9%) were at stage 1; 34 (1.6%) at stage 2; 791 (37.3%) at stage 3 and 140 (6.6%) at stage 4, although 53.6% of stage information was missing. Five-year survival was 2.1% for those who were not resected. The number of resections performed in each centre was not correlated with one-year survival. CONCLUSIONS: Despite improvements in the management of pancreatic cancer in England with the introduction of specialist centres, resection rates remain relatively low, and survival remains lower than in comparably wealthy countries.

Exploring variations in ovarian cancer survival by age and stage (ICBP SurvMark-2): A population-based study.

OBJECTIVE: The study aims to evaluate the differences in ovarian cancer survival by age and stage at diagnosis within and across seven high-income countries. METHODS: We analyzed data from 58,161 women diagnosed with ovarian cancer during 2010-2014, followed until 31 December 2015, from 21 population-based cancer registries in Australia, Canada, Denmark, Ireland, New Zealand, Norway, and United Kingdom. Comparisons of 1-year and 3-year age- and stage-specific net survival (NS) between countries were performed using the period analysis approach. RESULTS: Minor variation in the stage distribution was observed between countries, with most women being diagnosed with 'distant' stage (ranging between 64% in Canada and 71% in Norway). The 3-year all-ages NS ranged from 45 to 57% with Australia (56%) and Norway (57%) demonstrating the highest survival. The proportion of women with 'distant' stage was highest for those aged 65-74 and 75-99 years and varied markedly between countries (range:72-80% and 77-87%, respectively). The oldest age group had the lowest 3-year age-specific survival (20-34%), and women aged 65-74 exhibited the widest variation across countries (3-year NS range: 40-60%). Differences in survival between countries were particularly stark for the oldest age group with 'distant' stage (3-year NS range: 12% in Ireland to 24% in Norway). CONCLUSIONS: International variations in ovarian cancer survival by stage exist with the largest differences observed in the oldest age group with advanced disease. This finding endorses further research investigating international differences in access to and quality of treatment, and prevalence of comorbid conditions particularly in older women with advanced disease.

Practical Guidance for Measuring and Reporting Surgical Margins in Vulvar Cancer.

Surgical resection with free surgical margins is the cornerstone of successful primary treatment of vulvar squamous cell carcinoma (VSCC). In general reexcision is recommended when the minimum peripheral surgical margin (MPSM) is <8 mm microscopically. Pathologists are, therefore, required to report the minimum distance from the tumor to the surgical margin. Currently, there are no guidelines on how to make this measurement, as this is often considered straightforward. However, during the 2018 Annual Meeting of the British Association of Gynaecological Pathologists (BAGP), a discussion on this topic revealed a variety of opinions with regard to reporting and method of measuring margin clearance in VSCC specimens. Given the need for uniformity and the lack of guidance in the literature, we initiated an online survey in order to deliver a consensus-based definition of peripheral surgical margins in VSCC resections. The survey included questions and representative diagrams of peripheral margin measurements. In total, 57 pathologists participated in this survey. On the basis of consensus results, we propose to define MPSM in VSCC as the minimum distance from the peripheral edge of the invasive tumor nests toward the inked peripheral surgical margin reported in millimeters. This MPSM measurement should run through tissue and preferably be measured in a straight line. Along with MPSM, other relevant measurements such as depth of invasion or tumor thickness and distance to deep margins should be reported. This manuscript provides guidance to the practicing pathologist in measuring MPSM in VSCC resection specimens, in order to promote uniformity in measuring and reporting.

Impact of neuroendocrine morphology on cancer outcomes and stage at diagnosis: a UK nationwide cohort study 2013-2015.

BACKGROUND: The diagnosis of neuroendocrine neoplasms (NENs) is often delayed. This first UK population-based epidemiological study of NENs compares outcomes with non-NENs to identify any inequalities. METHODS: Age-standardised incidence rate (ASR), 1-year overall survival, hazard ratios and standardised mortality rates (SMRs) were calculated for all malignant NENs diagnosed 2013-2015 from UK national Public Health records. Comparison with non-NENs assessed 1-year overall survival (1YS) and association between diagnosis at stage IV and morphology. RESULTS: A total of 15,222 NENs were identified, with an ASR (2013-2015 combined) of 8.6 per 100,000 (95% CI 8.5-8.7); 4.6 per 100 000 (95% CI, 4.5-4.7) for gastro-entero-pancreatic (GEP) NENs. The 1YS was 75% (95% CI, 73.9-75.4) varying significantly by sex. Site and morphology were prognostic. NENs (predominantly small cell carcinomas) in the oesophagus, bladder, prostate, and female reproductive organs had a poorer outcome and were three times more likely to be diagnosed at stage IV than non-NENs. CONCLUSION: Advanced stage at diagnosis with significantly poorer outcomes of some NENs compared with non-NENs at the same anatomical site, highlight the need for improved access to specialist services and targeted service improvement.

A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal.

The classification of neuroendocrine neoplasms (NENs) differs between organ systems and currently causes considerable confusion. A uniform classification framework for NENs at any anatomical location may reduce inconsistencies and contradictions among the various systems currently in use. The classification suggested here is intended to allow pathologists and clinicians to manage their patients with NENs consistently, while acknowledging organ-specific differences in classification criteria, tumor biology, and prognostic factors. The classification suggested is based on a consensus conference held at the International Agency for Research on Cancer (IARC) in November 2017 and subsequent discussion with additional experts. The key feature of the new classification is a distinction between differentiated neuroendocrine tumors (NETs), also designated carcinoid tumors in some systems, and poorly differentiated NECs, as they both share common expression of neuroendocrine markers. This dichotomous morphological subdivision into NETs and NECs is supported by genetic evidence at specific anatomic sites as well as clinical, epidemiologic, histologic, and prognostic differences. In many organ systems, NETs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, and/or the presence of necrosis; NECs are considered high grade by definition. We believe this conceptual approach can form the basis for the next generation of NEN classifications and will allow more consistent taxonomy to understand how neoplasms from different organ systems inter-relate clinically and genetically.

Data Set for the Reporting of Carcinomas of the Cervix: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

A comprehensive pathologic report is essential for optimal patient management, cancer staging and prognostication. In many countries, proforma reports are used but the content of these is variable. The International Collaboration on Cancer Reporting is an alliance formed by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Partnership Against Cancer and the European Society of Pathology, for the purpose of developing standardized, evidence-based reporting data sets for each cancer site. This will reduce the global burden of cancer data set development and reduplication of effort by different international institutions that commission, publish and maintain standardized cancer-reporting data sets. The resultant standardization of cancer-reporting benefits not only those countries directly involved in the collaboration but also others not in a position to develop their own data sets. We describe the development of an evidence-based cancer data set by the International Collaboration on Cancer Reporting expert panel for the reporting of primary cervical carcinomas and present the "required" and "recommended" elements to be included in the pathology report as well as an explanatory commentary. This data set encompasses the International Federation of Obstetricians and Gynaecologists and Union for International Cancer Control staging systems for cervical neoplasms and the updated World Health Organization classification of gynecologic tumors. The data set also addresses controversial issues such as tumor grading and measurement, including measurement of multifocal carcinomas. The widespread implementation of this data set will facilitate consistent and accurate data collection, comparison of epidemiological and pathologic parameters between different populations, facilitate research, and hopefully result in improved patient management.