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The distribution of trial site locations may lead to disparities in geographic access and affect patient representativeness in clinical trials. We utilised trial data covering 1993-2022 from the National Institute for Health and Care Research (NIHR) Open Data Platform, 2011 and 2021 English Census and geographic data and English individual-patient cancer registry data for patients diagnosed with lymphoma between 1997 and 2017. To assess representation, we compared patient age and sex between trial participants and the incident population. We mapped the distance and travel times of English lower layer super output areas (LSOAs) to their nearest research active NHS Trusts and assessed associations between distance and travel times and the geographic and sociodemographic characteristics of the LSOAs. Trial participants were younger than the incident population and more likely to be male. The closest NHS Trust to more than half of English LSOAs was not research active. Greater LSOA mean age, male percent, White British percent, rurality and coastal/border status were positively associated with distance and travel time (at prespecified p < 0.05 level), while greater deprivation was negatively associated. Female and older lymphoma patients in England are underrepresented in trials, with the latter facing a higher burden of geographic barriers., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Menopausal hormone therapy (MHT) can alleviate menopausal symptoms but has been associated with an increased risk of breast cancer. MHT prescription should be preceded by individualised risk/benefit evaluation; however, data outlining the impact of family history alongside different MHT therapeutic approaches are lacking., Aim: To quantify the risks associated with MHT use in women with varying breast cancer family histories of developing and dying from breast cancer., Design and Setting: An epidemiological modelling study for women in England using the BOADICEA breast cancer prediction model and data relating to MHT use and breast cancer risk taken from research by the Collaborative Group on Hormonal Factors in Breast Cancer., Method: The risk of developing and dying from breast cancer between the ages of 50 and 80 years was modelled in women with four different breast cancer family history profiles: 'average', 'modest', 'intermediate', and 'strong' by using 1) background risks of breast cancer by age and family history, 2) relative risks for breast cancer associated with MHT use, and 3) 10-year breast cancer-specific net mortality rates. This study modelled use of combined oestrogen-progestogen MHT (cyclical or continuous) and oestrogen-only MHT., Results: For a woman of 'average' family history taking no MHT, the cumulative breast cancer risk (age 50-80 years) is 9.8%, and the risk of dying from the breast cancer is 1.7%. In this model, 5 years' exposure to combined-cyclical MHT (age 50-55 years) was calculated to increase these risks to 11.0% and 1.8%, respectively. For a woman with a 'strong' family history taking no MHT, the cumulative breast cancer risk is 19.6% (age 50-80 years), and the risk of dying from the breast cancer is 3.2%. With 5 years' exposure to MHT (age 50-55 years), this model showed that these risks increase to 22.4% and 3.5%, respectively., Conclusion: In this model, both family history and MHT are associated with increased risk of breast cancer. Estimates of the risks of breast cancer associated with MHT for women with different family histories can be used to support decision making around MHT prescription for women experiencing menopausal symptoms., (© The Authors.)

Objectives: To evaluate the long term risks of invasive breast cancer and death related to breast cancer after non-screen detected ductal carcinoma in situ. Risks for women in the general population and for women diagnosed with ductal carcinoma in situ via the screening programme were compared., Design: Population based cohort study., Setting: Data from the National Disease Registration Service., Participants: All 27 543 women in England who were diagnosed with ductal carcinoma in situ, outside the NHS breast screening programme, during 1990 to 2018., Main Outcome Measures: Incident invasive breast cancer and death caused by breast cancer., Results: By 31 December 2018, 3651 women with non-screen detected ductal carcinoma in situ had developed invasive breast cancer, more than four times higher than expected from national cancer incidence rates (ratio of observed to expected rate was 4.21 (95% conference interval 4.07 to 4.35)). The ratio of observed to expected rate of developing invasive breast cancer remained increased throughout follow-up among women aged <45-70 years. The 25 year cumulative risks of invasive breast cancer by age at diagnosis of ductal carcinoma in situ were 27.3% for <45 years, 25.2% for 45-49 years, 21.7% for 50-59 years, and 20.8% for 60-70 years. 908 women died of breast cancer, almost four times higher than that expected from breast cancer death rates in the general population (ratio of observed to expected rate 3.83 (3.59 to 4.09)). The ratio of observed to expected rate of mortality attributed to breast cancer remained increased throughout follow-up. The 25 year cumulative risks of breast cancer death by age at ductal carcinoma in situ diagnosis were 7.6% for <45 years, 5.8% for 45-49 years, 5.9% for 50-59 years, and 6.2% for 60-70 years. Among women aged 50-64 years, and therefore eligible for breast screening by the NHS, the ratio of observed to expected rate of invasive breast cancer in women with non-screen detected compared with screen detected ductal carcinoma in situ was 1.26 (95% conference interval 1.17 to 1.35), while the ratio for mortality from breast cancer was 1.37 (1.17 to 1.60). Among 22 753 women with unilateral ductal carcinoma in situ undergoing surgery, those who had mastectomy rather than breast conserving surgery had a lower 25 year cumulative rate of ipsilateral invasive breast cancer (mastectomy 8.2% (95% conference interval 7.0% to 9.4%), breast conserving surgery with radiotherapy 19.8% (16.2% to 23.4%), and breast conserving surgery with no radiotherapy recorded 20.6% (18.7% to 22.4%)). However, reductions did not translate into a lower 25 year cumulative rate of deaths attributable to breast cancer (mastectomy 6.5% (4.9% to 10.9%), breast conserving surgery with radiotherapy 8.6% (5.9% to 15.5%), breast conserving surgery with no radiotherapy recorded 7.8% (6.3% to 11.5%))., Conclusions: For at least 25 years after their diagnosis, women with non-screen detected ductal carcinoma in situ had higher long term risks of invasive breast cancer and breast cancer death than women in the general population. Additionally, they had higher long term risks than women with screen detected ductal carcinoma in situ. Mastectomy was associated with lower risks of invasive breast cancer than breast conserving surgery, even when accompanied by radiotherapy. However, risks of breast cancer death appeared similar for mastectomy, breast conserving surgery with radiotherapy, and breast conserving surgery with no radiotherapy recorded., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest and declare: funding from Cancer Research UK, Cancer Research UK Clinician Scientist Fellowship, the National Institute for Health Research Biomedical Research Centre, and the University of Oxford; no support from any organisation for the submitted work other than salaries from their employing institutions and the funding listed in the section above; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The National Congenital Anomaly and Rare Disease Registration Service (NCARDRS), part of National Disease Registration Service in National Health Service England, quality assures, curates and analyses individual data on the pregnancies, fetuses, babies, children and adults with congenital anomalies and rare diseases across England. The congenital anomaly (CA) register provides a resource for patients and their families, clinicians, researchers and public health professionals in furthering the understanding of CAs., Participants: NCARDRS registers CAs occurring in babies born alive and stillborn, fetal losses and terminations in England. NCARDRS collects data from secondary and tertiary healthcare providers, private providers and laboratories covering fetal medicine, maternity or paediatric services. Data describe the pregnancy, mother, baby and anomaly. Established in 2015, NCARDRS expanded CA registration coverage from 22% of total births in England in 2015 to national coverage, which was achieved in 2018. Prior to 2015, data collection was performed independently by regional registers in England; these data are also held by NCARDRS., Findings to Date: NCARDRS registers approximately 21 000 babies with CAs per year with surveillance covering around 600 000 total births, the largest birth coverage for a CA register globally. Data on prevalence, risk factors and survival for children with CAs are available. Data have been used in several peer-reviewed publications. Birth prevalence statistics, including public health indicators such as the association with maternal age, infant and perinatal mortality, are published annually. NCARDRS supports clinical audit for screening programmes and service evaluation., Future Plans: NCARDRS provides a valuable resource for the understanding of the epidemiology, surveillance, prevention and treatment of CAs. Currently, approximately 21 000 new registrations of babies or fetuses with suspected or confirmed CAs are added each year. Identifiers are collected, enabling linkage to routinely collected healthcare and population statistics, further enhancing the value of the data., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The percentage of cells staining positive for Ki67 is sometimes used for decision-making in patients with early invasive breast cancer (IBC). However, there is uncertainty regarding the most appropriate Ki67 cut points and the influence of interlaboratory measurement variability. We examined the relationship between breast cancer mortality and Ki67 both before and after accounting for interlaboratory variability and 8 patient and tumor characteristics., Methods: A multicenter cohort study of women with early IBC diagnosed during 2009-2016 in more than 20 NHS hospitals in England and followed until December 31, 2020., Results: Ki67 was strongly prognostic of breast cancer mortality in 8212 women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early IBC (Ptrend < .001). This relationship remained strong after adjustment for patient and tumor characteristics (Ptrend < .001). Standardization for interlaboratory variability did little to alter these results. For women with Ki67 scores of 0%-5%, 6%-10%, 11%-19%, and 20%-29% the corresponding 8-year adjusted cumulative breast cancer mortality risks were 3.3% (95% confidence interval [CI] = 2.8% to 4.0%), 3.7% (95% CI = 3.0% to 4.4%), 3.4% (95% CI = 2.8% to 4.1%), and 3.4% (95% CI = 2.8% to 4.1%), whereas for women with Ki67 scores of 30%-39% and 40%-100%, these risks were higher, at 5.1% (95% CI = 4.3% to 6.2%) and 7.7% (95% CI = 6.6% to 9.1) (Ptrend < .001). Similar results were obtained when the adjusted analysis was repeated with omission of pathological information about tumor size and nodal involvement, which would not be available preoperatively for patients being considered for neoadjuvant therapy., Conclusion: Our findings confirm the prognostic value of Ki67 scores of 30% or more in women with ER-positive, HER2-negative early IBC, irrespective of interlaboratory variability. These results also suggest that Ki67 may be useful to aid decision-making in the neoadjuvant setting., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Screening programmes utilising blood-based multi-cancer early detection (MCED) tests, which can detect a shared cancer signal from any site in the body with a single, low false-positive rate, could reduce cancer burden through early diagnosis., Methods: A natural history ('interception') model of cancer was previously used to characterise potential benefits of MCED screening (based on published performance of an MCED test). We built upon this using a two-population survival model to account for an increased risk of death from cfDNA-detectable cancers relative to cfDNA-non-detectable cancers. We developed another model allowing some cancers to metastasise directly from stage I, bypassing intermediate tumour stages. We used incidence and survival-by-stage data from the National Cancer Registration and Analysis Service in England to estimate longer-term benefits to a cohort screened between ages 50-79 years., Results: Estimated late-stage and mortality reductions were robust to a range of assumptions. With the least favourable dwell (sojourn) time and cfDNA status hazard ratio assumptions, we estimated, among 100,000 screened individuals, 67 (17%) fewer cancer deaths per year corresponding to 2029 fewer deaths in those screened between ages 50-79 years., Conclusion: Realising the potential benefits of MCED tests could substantially reduce late-stage cancer diagnoses and mortality., (© 2023. The Author(s).)

Purpose: The purpose of the Radiotherapy Dataset (RTDS) is to collect consistent and comparable data across all providers of National Health Service (NHS)-funded radiotherapy and to provide intelligence for service planning, commissioning, clinical practice and research., Participants: The RTDS is a mandated dataset requiring providers to collect and submit data monthly for patients treated in England. Data is available from 01 April 2009 to 2 months behind the calendar month.The National Disease Registration Service (NDRS) started receiving data from 01 April 2016. Prior to this, the National Clinical Analysis and Specialised Applications Team (NATCANSAT) were responsible for the RTDS. NDRS holds a copy of the NATCANSAT data for English NHS providers.The RTDS contains clinical information on the primary disease being treated, modality and intent of treatment, dose fractionation and hospital appointment details. Due to constraints in RTDS coding, linkage to the English National Cancer Registration dataset is beneficial., Findings to Date: The RTDS has been linked to the English National Cancer Registration and Systemic Anti-Cancer Therapy (SACT) datasets and to Hospital Episode Statistics (HES) to provide a more complete picture of the patient cancer pathway. Findings include a study to compare outcomes for patients treated with radical radiotherapy, an investigation of factors influencing 30-day mortality, assessing sociodemographic variation in the use of treatment and a study to assess the service impact of the COVID-19 pandemic. A range of other studies have been completed or are ongoing currently., Future Plans: The RTDS can be used for a variety of functions including cancer epidemiological studies to investigate inequalities in treatment access; provide service planning intelligence; monitor clinical practice; and support clinical trial design and recruitment. Collection is to continue indefinitely, with regular updates to the data specification to enable capture of more detailed information on radiotherapy planning and delivery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: It is proposed that, through restriction to individuals delineated as high risk, polygenic risk scores (PRSs) might enable more efficient targeting of existing cancer screening programmes and enable extension into new age ranges and disease types. To address this proposition, we present an overview of the performance of PRS tools (ie, models and sets of single nucleotide polymorphisms) alongside harms and benefits of PRS-stratified cancer screening for eight example cancers (breast, prostate, colorectal, pancreas, ovary, kidney, lung, and testicular cancer)., Methods: For this modelling analysis, we used age-stratified cancer incidences for the UK population from the National Cancer Registration Dataset (2016-18) and published estimates of the area under the receiver operating characteristic curve for current, future, and optimised PRS for each of the eight cancer types. For each of five PRS-defined high-risk quantiles (ie, the top 50%, 20%, 10%, 5%, and 1%) and according to each of the three PRS tools (ie, current, future, and optimised) for the eight cancers, we calculated the relative proportion of cancers arising, the odds ratios of a cancer arising compared with the UK population average, and the lifetime cancer risk. We examined maximal attainable rates of cancer detection by age stratum from combining PRS-based stratification with cancer screening tools and modelled the maximal impact on cancer-specific survival of hypothetical new UK programmes of PRS-stratified screening., Findings: The PRS-defined high-risk quintile (20%) of the population was estimated to capture 37% of breast cancer cases, 46% of prostate cancer cases, 34% of colorectal cancer cases, 29% of pancreatic cancer cases, 26% of ovarian cancer cases, 22% of renal cancer cases, 26% of lung cancer cases, and 47% of testicular cancer cases. Extending UK screening programmes to a PRS-defined high-risk quintile including people aged 40-49 years for breast cancer, 50-59 years for colorectal cancer, and 60-69 years for prostate cancer has the potential to avert, respectively, a maximum of 102, 188, and 158 deaths annually. Unstratified screening of the full population aged 48-49 years for breast cancer, 58-59 years for colorectal cancer, and 68-69 years for prostate cancer would use equivalent resources and avert, respectively, an estimated maximum of 80, 155, and 95 deaths annually. These maximal modelled numbers will be substantially attenuated by incomplete population uptake of PRS profiling and cancer screening, interval cancers, non-European ancestry, and other factors., Interpretation: Under favourable assumptions, our modelling suggests modest potential efficiency gain in cancer case detection and deaths averted for hypothetical new PRS-stratified screening programmes for breast, prostate, and colorectal cancer. Restriction of screening to high-risk quantiles means many or most incident cancers will arise in those assigned as being low-risk. To quantify real-world clinical impact, costs, and harms, UK-specific cluster-randomised trials are required., Funding: The Wellcome Trust., Competing Interests: Declaration of interests ADH acknowledges funding from the British Heart Foundation (AA/18/6/34223) and UKRI-NIHR (MR/V033867/1), is a member of the Advisory Group for the Industrial Strategy Challenge Fund Accelerating Detection of Disease Challenge, and a co-opted member of the National Institute for Health and Care Excellence Guideline update group for Cardiovascular disease: risk assessment and reduction, including lipid modification, CG181. CS acknowledges grants from AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Pfizer, Roche-Ventana, Invitae (previously Archer Dx—collaboration in minimal residual disease sequencing technologies), Ono Pharmaceutical, and Personalis; is chief investigator for the AZ MeRmaiD 1 and 2 clinical trials and is the Steering Committee chair; is co-chief investigator of the NHS Galleri trial funded by GRAIL and a paid member of GRAIL's Scientific Advisory Board; receives consultant fees from Achilles Therapeutics (and is also a Scientific Advisory Board member), Bicycle Therapeutics (and is also a Scientific Advisory Board member), Genentech, Medicxi, China Innovation Centre of Roche (formerly Roche Innovation Centre–Shanghai), Metabomed (until July, 2022), and the Sarah Cannon Research Institute; has received honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Illumina, MSD, Novartis, Pfizer, and Roche-Ventana; has previously held stock options in Apogen Biotechnologies and GRAIL, and currently has stock options in Epic Bioscience and Bicycle Therapeutics, and has stock options and is co-founder of Achilles Therapeutics; has a patents issued for an immune checkpoint intervention in cancer (PCT/EP2016/071471), in treating cancer based on identification of clonal neo-antigens (PCT/EP2016/059401), in lung cancer detection (PCT/US2017/028013), in detecting tumour recurrence (PCT/GB2017/053289), in treating cancer (PCT/EP2016/059401), in treating cancer by targeting insertion–deletion mutations (PCT/GB2018/051893), in identifying insertion–deletion mutation targets (PCT/GB2018/051892), in determining whether an HLA allele is lost in a tumour (PCT/GB2018/052004), in identifying responders to cancer treatment (PCT/GB2018/051912), and in predicting survival rates for cancer patients (PCT/GB2020/050221). CT has received personal fees from AstraZeneca and Roche. HH has received personal fees from AstraZeneca. KS has received personal fees from BUPA, AstraZeneca, Pfizer, Merck, and AXA. MM receives royalties from authorship of books and book chapters, in addition to freelance journalism; consulting fees from her work as an NHS general practitioner; and fees for acting as an expert witness to the Infected Blood Inquiry and for lectures at Oxford and Glasgow Universities. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

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., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background and Objectives: Uptake of breast cancer screening has been decreasing in England since 2007. However, the associated factors are unclear. On the other hand, survival among breast cancer patients have recently increased. We conducted a quasi-experimental analysis to test whether the trend-change in proportional incidence of non-screened cancers coincided with that in five-year net-survival., Methods: We extracted population-based proportional incidence and age-standardized five-year net-survival data from Public Health England that included English women with invasive breast cancer diagnosed during 1995-2011 (linked to death certificates, followed through 2016). Piece-wise log-linear models with change-point/joinpoint were used to estimate temporal trends., Results: Among 254,063 women in England with invasive breast cancer diagnosed during 1995-2011, there was downward-to-upward trend-change in proportional incidence of non-screened breast cancers (annual percent change [APC]=5.6 after 2007 versus APC=-3.5 before 2007, p <0.001) in diagnosis-year 2007, when a steeper upward-trend in age-standardized five-year net survival started (APC=5.7 after 2007/2008 versus APC=0.3 before 2007/2008, p< 0.001). Net-survival difference of screened versus non-screened cancers also significantly narrowed (18% in 2007/2008 versus 5% in 2011). Similar associations were found in all strata of race, cancer stage, grade, and histology, except in Black patients or patients with stage I, stage III, or grade I cancer., Conclusions: There was a downward-to-upward trend-change in proportional incidence of non-screened breast cancers in 2007 that coincided with a steeper upward-trend in age-standardized five-year net survival among English women in 2007. Survival benefits of breast cancer screening decreased during 2007-2011. The data support reduction of breast cancer screening in some patients, but future validation studies are warranted., Competing Interests: Conflict of interest One of the authors, LZ, has been a deputy Editor-in-Chief of Journal of Clinical and Translational Pathology since May 2021.The other authors have nothing to disclose.

Background: Ethnic minority women are commonly reported to have more aggressive breast cancer than White women, but there is little contemporary national evidence available., Methods: We analysed data from the National Cancer Registration and Analysis Service on women diagnosed with invasive breast cancer during 2013-2018. Multivariable logistic regression yielded adjusted odds ratios (and 95% confidence intervals) of less favourable tumour characteristics (high stage, high grade, ER negative, Her2 positive) by ethnicity (black African, black Caribbean, Indian, Pakistani and white) in younger (30-46 years) and older (53-70 years) women., Results: In 24,022 women aged 30-46 at diagnosis, all ethnic minority groups apart from Indian women had a significantly greater odds of certain less favourable tumour characteristics compared to white women in fully adjusted models. In 92,555 women aged 53-70, all ethnic minorities had a significantly greater adjusted odds of several of the less favourable tumour characteristics. These differences were most marked in black African and black Caribbean women., Conclusions: Ethnic minority women are at greater risk of breast cancers with less favourable characteristics, even after allowing for age and other potential confounders. These differences are greater in older than younger women, and in the Black rather than South Asian ethnic groups., (© 2021. The Author(s).)

Objective: To evaluate the impact of faecal immunochemical testing (FIT) prioritisation to mitigate the impact of delays in the colorectal cancer (CRC) urgent diagnostic (2-week-wait (2WW)) pathway consequent from the COVID-19 pandemic., Design: We modelled the reduction in CRC survival and life years lost resultant from per-patient delays of 2-6 months in the 2WW pathway. We stratified by age group, individual-level benefit in CRC survival versus age-specific nosocomial COVID-19-related fatality per referred patient undergoing colonoscopy. We modelled mitigation strategies using thresholds of FIT triage of 2, 10 and 150 µg Hb/g to prioritise 2WW referrals for colonoscopy. To construct the underlying models, we employed 10-year net CRC survival for England 2008-2017, 2WW pathway CRC case and referral volumes and per-day-delay HRs generated from observational studies of diagnosis-to-treatment interval., Results: Delay of 2/4/6 months across all 11 266 patients with CRC diagnosed per typical year via the 2WW pathway were estimated to result in 653/1419/2250 attributable deaths and loss of 9214/20 315/32 799 life years. Risk-benefit from urgent investigatory referral is particularly sensitive to nosocomial COVID-19 rates for patients aged >60. Prioritisation out of delay for the 18% of symptomatic referrals with FIT >10 µg Hb/g would avoid 89% of these deaths attributable to presentational/diagnostic delay while reducing immediate requirement for colonoscopy by >80%., Conclusions: Delays in the pathway to CRC diagnosis and treatment have potential to cause significant mortality and loss of life years. FIT triage of symptomatic patients in primary care could streamline access to colonoscopy, reduce delays for true-positive CRC cases and reduce nosocomial COVID-19 mortality in older true-negative 2WW referrals. However, this strategy offers benefit only in short-term rationalisation of limited endoscopy services: the appreciable false-negative rate of FIT in symptomatic patients means most colonoscopies will still be required., Competing Interests: Competing interests: ML has received honoraria from Pfizer, EMD Merck Serono and Roche for speaking honoraria unrelated to this work. ML has received an unrestricted educational grant from Pfizer for research unrelated to this work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: During the COVID-19 lockdown, referrals via the 2-week-wait urgent pathway for suspected cancer in England, UK, are reported to have decreased by up to 84%. We aimed to examine the impact of different scenarios of lockdown-accumulated backlog in cancer referrals on cancer survival, and the impact on survival per referred patient due to delayed referral versus risk of death from nosocomial infection with severe acute respiratory syndrome coronavirus 2., Methods: In this modelling study, we used age-stratified and stage-stratified 10-year cancer survival estimates for patients in England, UK, for 20 common tumour types diagnosed in 2008-17 at age 30 years and older from Public Health England. We also used data for cancer diagnoses made via the 2-week-wait referral pathway in 2013-16 from the Cancer Waiting Times system from NHS Digital. We applied per-day hazard ratios (HRs) for cancer progression that we generated from observational studies of delay to treatment. We quantified the annual numbers of cancers at stage I-III diagnosed via the 2-week-wait pathway using 2-week-wait age-specific and stage-specific breakdowns. From these numbers, we estimated the aggregate number of lives and life-years lost in England for per-patient delays of 1-6 months in presentation, diagnosis, or cancer treatment, or a combination of these. We assessed three scenarios of a 3-month period of lockdown during which 25%, 50%, and 75% of the normal monthly volumes of symptomatic patients delayed their presentation until after lockdown. Using referral-to-diagnosis conversion rates and COVID-19 case-fatality rates, we also estimated the survival increment per patient referred., Findings: Across England in 2013-16, an average of 6281 patients with stage I-III cancer were diagnosed via the 2-week-wait pathway per month, of whom 1691 (27%) would be predicted to die within 10 years from their disease. Delays in presentation via the 2-week-wait pathway over a 3-month lockdown period (with an average presentational delay of 2 months per patient) would result in 181 additional lives and 3316 life-years lost as a result of a backlog of referrals of 25%, 361 additional lives and 6632 life-years lost for a 50% backlog of referrals, and 542 additional lives and 9948 life-years lost for a 75% backlog in referrals. Compared with all diagnostics for the backlog being done in month 1 after lockdown, additional capacity across months 1-3 would result in 90 additional lives and 1662 live-years lost due to diagnostic delays for the 25% backlog scenario, 183 additional lives and 3362 life-years lost under the 50% backlog scenario, and 276 additional lives and 5075 life-years lost under the 75% backlog scenario. However, a delay in additional diagnostic capacity with provision spread across months 3-8 after lockdown would result in 401 additional lives and 7332 life-years lost due to diagnostic delays under the 25% backlog scenario, 811 additional lives and 14 873 life-years lost under the 50% backlog scenario, and 1231 additional lives and 22 635 life-years lost under the 75% backlog scenario. A 2-month delay in 2-week-wait investigatory referrals results in an estimated loss of between 0·0 and 0·7 life-years per referred patient, depending on age and tumour type., Interpretation: Prompt provision of additional capacity to address the backlog of diagnostics will minimise deaths as a result of diagnostic delays that could add to those predicted due to expected presentational delays. Prioritisation of patient groups for whom delay would result in most life-years lost warrants consideration as an option for mitigating the aggregate burden of mortality in patients with cancer., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Cancer survival statistics are typically reported by using measures discounting the impact of other-cause mortality, such as net survival. This is a hypothetical measure and is interpreted as excluding the possibility of cancer patients dying from other causes. Crude probability of death partitions the all-cause probability of death into deaths from cancer and other causes., Methods: The National Cancer Registration and Analysis Service is the single cancer registry for England. In 2006-2015, 1,590,477 malignant tumours were diagnosed for breast, colorectal, lung, melanoma and prostate cancer in adults. We used a relative survival framework, with a period approach, providing estimates for up to 10-year survival. Mortality was partitioned into deaths due to cancer or other causes. Unconditional and conditional (on surviving 1-years and 5-years) crude probability of death were estimated for the five cancers., Results: Elderly patients who survived for a longer period before dying were more likely to die from other causes of death (except for lung cancer). For younger patients, deaths were almost entirely due to the cancer., Conclusion: There are different measures of survival, each with their own strengths and limitations. Careful choices of survival measures are needed for specific scenarios to maximise the understanding of the data.

Introduction: National cancer registration data were linked to the Primary Care Prescription Database (PCPD) in England. The level of endocrine therapy (ET) prescribed in women after a diagnosis of breast cancer was studied., Materials and Methods: Cancer registrations for women diagnosed with breast cancer during 1995-2015, who survived to 31st March 2015, were linked to ET prescriptions issued during April-July 2015., Results: Among 369 277 survivors of breast cancer diagnosed during 1995-2015, 37% were prescribed ET during April-July 2015. Among women whose breast cancer diagnosis was after 31st July 2010, 81% of those recorded with oestrogen receptor positive (ER+ve) disease were prescribed ET compared with only 6% of those with ER-ve disease. Younger women usually received tamoxifen and older women usually received aromatase inhibitors., Discussion: The pattern of ET use observed in these data corresponds to that expected. This provides confidence in the potential of the PCPD for epidemiological research., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Aims: Adjuvant chemotherapy is recommended as a treatment for women with high recurrence risk early breast cancer. Older women are less likely to receive chemotherapy than younger women. This study investigated the impact of chemotherapy on breast cancer-specific survival in women aged 70 + years using English registry data., Materials and Methods: Cancer registration data were obtained from two English regions from 2002 to 2012 (n = 29 728). The impact of patient-level characteristics on the probability of receiving adjuvant chemotherapy was explored using logistic regression. Survival modelling was undertaken to show the effect of chemotherapy and age/health status on breast cancer-specific survival. Missing data were handled using multiple imputation., Results: In total, 11 735 surgically treated early breast cancer patients were identified. Use of adjuvant chemotherapy has increased over time. Younger age at diagnosis, increased nodal involvement, tumour size and grade, oestrogen receptor-negative or human epidermal growth factor receptor 2-positive disease were all associated with increased probability of receiving chemotherapy. Chemotherapy was associated with a significant reduction in the hazard of breast cancer-specific mortality in women with high risk cancer, after adjusting for patient-level characteristics (hazard ratio 0.74, 95% confidence interval 0.67-0.81)., Discussion: Chemotherapy is associated with an improved breast cancer-specific survival in older women with early breast cancer at high risk of recurrence . Lower rates of chemotherapy use in older women may, therefore, contribute to inferior cancer outcomes. Decisions on potential benefits for individual patients should be made on the basis of life expectancy, treatment tolerance and patient preference., (Copyright © 2019. Published by Elsevier Ltd.)

Importance: Cutaneous squamous cell carcinoma (cSCC) is the most common skin cancer with metastatic potential, but epidemiologic data are poor. Changes to the National Cancer Registration and Analysis Service (NCRAS) in England have allowed more accurate data analysis of primary and metastatic cSCC since 2013., Objective: To assess the national incidence of cSCC and metastatic cSCC (mcSCC) in England from 2013 through 2015., Design, Setting, and Participants: This national population-based study identified a cohort of patients with cSCC and mcSCC in England from January 1, 2013, through December 31, 2015. Patients were identified using diagnostic codes derived from pathology reports in the NCRAS. Data were analyzed from March 1, 2017, through March 1, 2018., Main Outcomes and Measures: Incidence rates across sex and risk factors for cSCC were derived from the NCRAS data. Risk of occurrence of mcSCC among the population with cSCC was assessed with Cox proportional hazards regression analysis to determine indicators of mcSCC., Results: Among the 76 977 patients with first primary cSCC in 2013 through 2015 (62.7% male; median age, 80 years [interquartile range, 72-86 years]), the age-standardized rates for the first registered cSCC in England from 2013 through 2015 were 77.3 per 100 000 person-years (PY) (95% CI, 76.6-78.0) in male patients and 34.1 per 100 000 PY (95% CI, 33.7-34.5) in female patients. Increased primary cSCC tumor count was observed in older, white male patients in lower deprivation quintiles. After a maximum follow-up of 36 months, cumulative incidence of mcSCC developed in 1.1% of women and 2.4% of men with a primary cSCC. Significant increases in the risk of metastasis with adjusted hazard rates of approximately 2.00 were observed in patients who were aged 80 to 89 years (hazard ratio [HR], 1.23; 95% CI, 1.07-1.43), 90 years or older (HR, 1.35; 95% CI, 1.09-1.66), male (HR, 1.79; 95% CI, 1.52-2.10), immunosuppressed (HR, 1.99; 95% CI, 1.64-2.42), and in higher deprivation quintiles (HR for highest quintile, 1.64; 95% CI, 1.35-2.00). Primary cSCC located on the ear (HR, 1.70; 95% CI, 1.42-2.03) and lip (HR, 1.85; 95% CI, 1.29-2.63) were at highest risk of metastasis., Conclusions and Relevance: This study presents the first national study of the incidence of mcSCC. With limited health care resources and an aging population, accurate epidemiologic data are essential for informing future health care planning, identifying high-risk patients, and evaluating skin cancer prevention policies.

Background: Older patients are poorly represented in breast cancer research and guidelines do not provide evidence based recommendations for this specific group. We compared treatment strategies and survival outcomes between European countries and assessed whether variance in treatment patterns may be associated with variation in survival., Methods: Population-based study including patients aged ≥ 70 with non-metastatic BC from cancer registries from the Netherlands, Belgium, Ireland, England and Greater Poland. Proportions of local and systemic treatments, five-year relative survival and relative excess risks (RER) between countries were calculated., Results: In total, 236,015 patients were included. The proportion of stage I BC receiving endocrine therapy ranged from 19.6% (Netherlands) to 84.6% (Belgium). The proportion of stage III BC receiving no breast surgery varied between 22.0% (Belgium) and 50.8% (Ireland). For stage I BC, relative survival was lower in England compared with Belgium (RER 2.96, 95%CI 1.30-6.72, P < .001). For stage III BC, England, Ireland and Greater Poland showed significantly worse relative survival compared with Belgium., Conclusions: There is substantial variation in treatment strategies and survival outcomes in elderly with BC in Europe. For early-stage BC, we observed large variation in endocrine therapy but no variation in relative survival, suggesting potential overtreatment. For advanced BC, we observed higher survival in countries with lower proportions of omission of surgery, suggesting potential undertreatment.

Background: In the re-organisation of cancer registration in England in 2012, a high priority was given to the recording of cancer stage and other prognostic clinical data items., Methods: We extracted 86 852 breast cancer records for women resident in England and diagnosed during 2012-2013. Information on age, ethnicity, socio-economic status, comorbidity, tumour stage, grade, morphology and oestrogen, progesterone and HER2 receptor status was included. The two-year cumulative risk of death from any cause was estimated with the Kaplan-Meier method, and univariate and multivariate Cox proportional hazards regressions were used to estimate hazard ratios (HR) and their 95% confidence intervals (95% CI). The follow-up ended on 31 December 2014., Results: The completeness of registration for prognostic variables was generally high (around 80% or higher), but it was low for progesterone receptor status (41%). Women with negative receptor status for each of the oestrogen, progesterone and HER2 receptors (triple-negative cancers) had an adjusted HR for death of 2.00 (95%CI 1.84-2.17). Black women had an age-adjusted HR of 1.77 (1.48-2.13) compared with White women., Conclusions: The excess mortality of Black women with breast cancer has contributions from socio-economic factors, stage distribution and tumour biology. The study illustrates the richness of detail in the national cancer registration data. This allows for analysis of cancer outcomes at a high level of resolution, and may form the basis for risk stratification., Competing Interests: Katherine Henson has in the past been an employee of BUPA. Ruth Jack and Elizabeth Davies have received research funding for an unrelated project from Hospital Corporation of America International. All other authors declare no conflict of interest. The views expressed are those of the authors and not necessarily those of CRUK, the NHS, the NIHR or the Department of Health. The researchers were independent of the funders, and the researchers alone interpreted the data and decided to publish.

Background: The role of age as a prognostic factor has been examined in single institutional studies and in larger data sets from the SEER database, showing a survival advantage for younger versus adult patients with synovial sarcoma (SS). To further assess the role of age, socioeconomic status and other prognostic factors on outcome for SS, we analysed a contemporary all-age population-based cohort of patients with SS registered in England., Methods: The data on 1318 synovial sarcomas diagnosed in England between 1985 and 2009 were retrospectively analysed for incidence, and the effect of age, patient characteristics and deprivation on outcome using both univariate and multivariate analysis., Results: The incidence of SS increased to 1.4 per million over the time period, the numbers diagnosed in patients under 10 years of age were small. The site or incidence of metastases did not vary between age groups. There were, however, significant differences (p < 0.05) in the 5-year relative survival rates between patients aged 0-19 years and those ≥20 years of age, 76 % and 53 % respectively. Survival was better in localised tumours at an extremity site. In multivariate analysis higher mortality occurred in older patients, non-extremity site, presence of metastases, female adults and a higher deprivation score., Conclusions: Synovial sarcoma in children/teenagers compared with adults, have a similar clinical presentation in this population-based series, but a superior outcome. The finding of socioeconomic deprivation affecting outcome in SS needs further exploration in a complete and contemporary dataset, where all prognostic variables are present.