Risks of second primary cancers among 584,965 female and male breast cancer survivors in England: a 25-year retrospective cohort study.

Background: Second primary cancers (SPCs) after breast cancer (BC) present an increasing public health burden, with little existing research on socio-demographic, tumour, and treatment effects. We addressed this in the largest BC survivor cohort to date, using a novel linkage of National Disease Registration Service datasets. Methods: The cohort included 581,403 female and 3562 male BC survivors diagnosed between 1995 and 2019. We estimated standardized incidence ratios (SIRs) for combined and site-specific SPCs using incidences for England, overall and by age at BC and socioeconomic status. We estimated incidences and Kaplan-Meier cumulative risks stratified by age at BC, and assessed risk variation by socio-demographic, tumour, and treatment characteristics using Cox regression. Findings: Both genders were at elevated contralateral breast (SIR: 2.02 (95% CI: 1.99-2.06) females; 55.4 (35.5-82.4) males) and non-breast (1.10 (1.09-1.11) females, 1.10 (1.00-1.20) males) SPC risks. Non-breast SPC risks were higher for females younger at BC diagnosis (SIR: 1.34 (1.31-1.38) <50 y, 1.07 (1.06-1.09) ≥50 y) and more socioeconomically deprived (SIR: 1.00 (0.98-1.02) least deprived quintile, 1.34 (1.30-1.37) most). Interpretation: Enhanced SPC surveillance may benefit BC survivors, although specific recommendations require more detailed multifactorial risk and cost-benefit analyses. The associations between deprivation and SPC risks could provide clinical management insights. Funding: CRUK Catalyst Award CanGene-CanVar (C61296/A27223). Cancer Research UK grant: PPRPGM-Nov 20∖100,002. This work was supported by core funding from the NIHR Cambridge Biomedical Research Centre (NIHR203312)]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Venous thromboembolism risk in amyotrophic lateral sclerosis: a hospital record-linkage study.

BACKGROUND: Venous thromboembolism (VTE) can occur in amyotrophic lateral sclerosis (ALS) and pulmonary embolism causes death in a minority of cases. The benefits of preventing VTE must be weighed against the risks. An accurate estimate of the incidence of VTE in ALS is crucial to assessing this balance. METHODS: This retrospective record-linkage cohort study derived data from the Hospital Episode Statistics database, covering admissions to England's hospitals from 1 April 2003 to 31 December 2019 and included 21 163 patients with ALS and 17 425 337 controls. Follow-up began at index admission and ended at VTE admission, death or 2 years (whichever came sooner). Adjusted HRs (aHRs) for VTE were calculated, controlling for confounders. RESULTS: The incidence of VTE in the ALS cohort was 18.8/1000 person-years. The relative risk of VTE in ALS was significantly greater than in controls (aHR 2.7, 95% CI 2.4 to 3.0). The relative risk of VTE in patients with ALS under 65 years was five times higher than controls (aHR 5.34, 95% CI 4.6 to 6.2), and higher than that of patients over 65 years compared with controls (aHR 1.86, 95% CI 1.62 to 2.12). CONCLUSIONS: Patients with ALS are at a higher risk of developing VTE, but this is similar in magnitude to that reported in other chronic neurological conditions associated with immobility, such as multiple sclerosis, which do not routinely receive VTE prophylaxis. Those with ALS below the median age of symptom onset have a notably higher relative risk. A reappraisal of the case for routine antithrombotic therapy in those diagnosed with ALS now requires a randomised controlled trial.

The comprehensive English National Lynch Syndrome Registry: development and description of a new genomics data resource.

Background: Lynch Syndrome (LS) is a cancer predisposition syndrome caused by constitutional pathogenic variants in the mismatch repair (MMR) genes. To date, fragmentation of clinical and genomic data has restricted understanding of national LS ascertainment and outcomes, and precluded evaluation of NICE guidance on testing and management. To address this, via collaboration between researchers, the National Disease Registration Service (NDRS), NHS Genomic Medicine Service Alliances (GMSAs), and NHS Regional Clinical Genetics Services, a comprehensive registry of LS carriers in England has been established. Methods: For comprehensive ascertainment of retrospectively identified MMR pathogenic variant (PV) carriers (diagnosed prior to January 1, 2023), information was retrieved from all clinical genetics services across England, then restructured, amalgamated, and validated via a team of trained experts in NDRS. An online submission portal was established for prospective ascertainment from January 1, 2023. The resulting data, stored in a secure database in NDRS, were used to investigate the demographic and genetic characteristics of the cohort, censored at July 25, 2023. Cancer outcomes were investigated via linkage to the National Cancer Registration Dataset (NCRD). Findings: A total of 11,722 retrospective and 570 prospective data submissions were received, resulting in a comprehensive English National Lynch Syndrome Registry (ENLSR) comprising 9030 unique individuals. The most frequently identified pathogenic MMR genes were MSH2 and MLH1 at 37.2% (n = 3362) and 29.1% (n = 2624), respectively. 35.9% (n = 3239) of the ENLSR cohort received their LS diagnosis before their first cancer diagnosis (presumptive predictive germline test). Of these, 6.3% (n = 204) developed colorectal cancer, at a median age of initial diagnosis of 51 (IQR 40-62), compared to 73 years (IQR 64-80) in the general population (p < 0.0001). Interpretation: The ENLSR represents the first comprehensive national registry of PV carriers in England and one of the largest cohorts of MMR PV carriers worldwide. The establishment of a secure, centralised infrastructure and mechanism for routine registration of newly identified carriers ensures sustainability of the data resource. Funding: This work was funded by the Wellcome Trust, Cancer Research UK and Bowel Cancer UK. The funder of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.

Colorectal polyp outcomes after participation in the seAFOod polyp prevention trial: Evidence of rebound elevated colorectal polyp risk after short-term aspirin use.

BACKGROUND: The seAFOod polyp prevention trial was a randomised, placebo-controlled, 2 × 2 factorial trial of aspirin 300 mg and eicosapentaenoic acid (EPA) 2000 mg daily in individuals who had a screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Aspirin treatment was associated with a 20% reduction in colorectal polyp number at BCSP surveillance colonoscopy 12 months later. It is unclear what happens to colorectal polyp risk after short-term aspirin use. AIM: To investigate colorectal polyp risk according to the original trial treatment allocation, up to 6 years after trial participation. METHODS: All seAFOod trial participants were scheduled for further BCSP surveillance and provided informed consent for the collection of colonoscopy outcomes. We linked BCSP colonoscopy data to trial outcomes data. RESULTS: In total, 507 individuals underwent one or more colonoscopies after trial participation. Individuals grouped by treatment allocation were well matched for clinical characteristics, follow-up duration and number of surveillance colonoscopies. The polyp detection rate (PDR; the number of individuals who had ≥1 colorectal polyp detected) after randomization to placebo aspirin was 71.1%. The PDR was 80.1% for individuals who had received aspirin (odds ratio [OR] 1.13 [95% confidence interval 1.02, 1.24]; p = 0.02). There was no difference in colorectal polyp outcomes between individuals who had been allocated to EPA compared with its placebo (OR for PDR 1.00 [0.91, 1.10]; p = 0.92). CONCLUSION: Individuals who received aspirin in the seAFOod trial demonstrated increased colorectal polyp risk during post-trial surveillance. Rebound elevated neoplastic risk after short-term aspirin use has important implications for aspirin cessation driven by age-related bleeding risk. ISRCTN05926847.

Patterns of chemotherapy use and outcomes in advanced non-small cell lung cancer by age in England: A retrospective analysis of the population-based Systemic Anti-Cancer Treatment (SACT) dataset.

INTRODUCTION: We described the patterns of chemotherapy use and outcomes in patients diagnosed with stage III or IV non-small cell lung cancer (NSCLC) by age in England. MATERIALS AND METHODS: In this retrospective population-based study, we included 20,716 (62% stage IV) patients with NSCLC diagnosed from 2014 to 2017 treated with chemotherapy. We used the Systemic Anti-Cancer Treatment (SACT) dataset to describe changes in treatment plan and estimated 30 and 90-day mortality rates and median, 6-, and 12-month overall survival (OS) using Kaplan Meier estimator for patients aged <75 and ≥ 75 by stage. Using flexible hazard regression models we assessed the impact of age, stage, treatment intent (stage III), and performance status on survival. RESULTS: Patients aged ≥75 years were less likely to receive two or more regimens, more likely to have their treatment modified because of comorbidities and their doses reduced compared to younger patients. However, early mortality rates and overall survival were similar across ages, apart from the oldest patients with stage III disease. DISCUSSION: This observational study demonstrates that age is associated with treatment patterns in an older population with advanced NSCLC in England. Although this reflects a pre-immunotherapy period, given the median age of NSCLC patients and increasingly older population, these results suggest older patients (>75 yrs) may benefit from more intense treatments.

Age-related differences in colon and rectal cancer survival by stage, histology, and tumour site: An analysis of United States SEER-18 data.

Age-related differences in colon and rectal cancer survival have been observed, even after accounting for differences in background mortality. To determine how stage, tumour site, and histology contribute to these differences, we extracted age-specific one-year relative survival ratio (RS) stratified by these factors. We used colon and rectal cancer cases diagnosed between 2012 and 2016 from 18 United States Surveillance Epidemiology and End Results cancer registries. For colon cancer, 1-year RS ranged from 87.8 % [95 % Confidence Interval: 87.5-88.2] in the 50-64-year-olds to 62.3 % [61.3-63.3] in 85-99-year-olds and for rectal cancer ranged from 92.3 % [91.8-92.7] to 65.0 % [62.3-67.5]. With respect to stage, absolute differences in RS between 50-64-year-olds and 75-84-year-olds increased with increasing stage (from 6 [5-7] %-points in localised disease to 27 [25-29] %-points in distant disease) and were the highest for cancers of unknown stage (> 28 %-points). Age-related differences in survival were smallest for persons with tumours in the right-sided colon (8 [7-9] %-points) and largest for tumours of the colon without tumour site further specified (25 [21-29] %-points). With respect to histology, differences ranged from 7.4 % to 10.6 %-points for cancers with one of the three primary histologies (adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma) and were several-fold higher (42 %-points) for those with unknown/other histology (< 6 % of cases). Because age-related differences in survival were observed for all histologies and tumour sites, RS differences are unlikely to be driven by differences in the distribution of these factors by age. Differences in stage distribution by age are likely to contribute toward age-related differences in survival. Within stage groups, age differences in survival could be explained by frailty and/or therapy. Future studies incorporating data on treatment and geriatric conditions including frailty and comorbidity would support further understanding of the age gap in colon and rectal cancer survival.

Age-related differences in cancer relative survival in the United States: A SEER-18 analysis.

Cancer survival has improved since the 1990s, but to different extents across age groups, with a disadvantage for older adults. We aimed to quantify age-related differences in relative survival (RS-1-year and 1-year conditioning on surviving 1 year) for 10 common cancer types by stage at diagnosis. We used data from 18 United States Surveillance Epidemiology and End Results cancer registries and included cancers diagnosed in 2012 to 2016 followed until December 31, 2017. We estimated absolute differences in RS between the 50 to 64 age group and the 75 to 84 age group. The smallest differences were observed for prostate and breast cancers (1.8%-points [95% confidence interval (CI): 1.5-2.1] and 1.9%-points [95% CI: 1.5-2.3], respectively). The largest was for ovarian cancer (27%-points, 95% CI: 24-29). For other cancers, differences ranged between 7 (95% CI: 5-9, esophagus) and 18%-points (95% CI: 17-19, pancreas). Except for pancreatic cancer, cancer type and stage combinations with very high (>95%) or very low (<40%) 1-year RS tended to have smaller age-related differences in survival than those with mid-range prognoses. Age-related differences in 1-year survival conditioning on having survived 1-year were small for most cancer and stage combinations. The broad variation in survival differences by age across cancer types and stages, especially in the first year, age-related differences in survival are likely influenced by amenability to treatment. Future work to measure the extent of age-related differences that are avoidable, and identify how to narrow the survival gap, may have most benefit by prioritizing cancers with relatively large age-related differences in survival (eg, stomach, esophagus, liver and pancreas).

Immortal-time bias in older vs younger age groups: a simulation study with application to a population-based cohort of patients with colon cancer.

BACKGROUND: In observational studies, the risk of immortal-time bias (ITB) increases with the likelihood of early death, itself increasing with age. We investigated how age impacts the magnitude of ITB when estimating the effect of surgery on 1-year overall survival (OS) in patients with Stage IV colon cancer aged 50-74 and 75-84 in England. METHODS: Using simulations, we compared estimates from a time-fixed exposure model to three statistical methods addressing ITB: time-varying exposure, delayed entry and landmark methods. We then estimated the effect of surgery on OS using a population-based cohort of patients from the CORECT-R resource and conducted the analysis using the emulated target trial framework. RESULTS: In simulations, the magnitude of ITB was larger among older patients when their probability of early death increased or treatment was delayed. The bias was corrected using the methods addressing ITB. When applied to CORECT-R data, these methods yielded a smaller effect of surgery than the time-fixed exposure approach but effects were similar in both age groups. CONCLUSION: ITB must be addressed in all longitudinal studies, particularly, when investigating the effect of exposure on an outcome in different groups of people (e.g., age groups) with different distributions of exposure and outcomes.

Effects of the COVID-19 pandemic on secondary care for cardiovascular disease in the UK: an electronic health record analysis across three countries.

BACKGROUND: Although morbidity and mortality from COVID-19 have been widely reported, the indirect effects of the pandemic beyond 2020 on other major diseases and health service activity have not been well described. METHODS AND RESULTS: Analyses used national administrative electronic hospital records in England, Scotland, and Wales for 2016-21. Admissions and procedures during the pandemic (2020-21) related to six major cardiovascular conditions [acute coronary syndrome (ACS), heart failure (HF), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), aortic aneurysm (AA), and venous thromboembolism(VTE)] were compared with the annual average in the pre-pandemic period (2016-19). Differences were assessed by time period and urgency of care.In 2020, there were 31 064 (-6%) fewer hospital admissions [14 506 (-4%) fewer emergencies, 16 560 (-23%) fewer elective admissions] compared with 2016-19 for the six major cardiovascular diseases (CVDs) combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries [-10 996 (-15%) fewer admissions]. However, these reductions were offset by higher than expected total emergency admissions [+25 878 (+6%) higher admissions], notably for HF and stroke in England, and for VTE in all three countries. Analyses for procedures showed similar temporal variations to admissions. CONCLUSION: The present study highlights increasing emergency cardiovascular admissions during the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.

Inflammatory Bowel Disease-Associated Colorectal Cancer Epidemiology and Outcomes: An English Population-Based Study.

INTRODUCTION: Patients with inflammatory bowel diseases (IBDs) of the colon are at an increased risk of colorectal cancer (CRC). This study investigates the epidemiology of IBD-CRC and its outcomes. METHODS: Using population data from the English National Health Service held in the CRC data repository, all CRCs with and without prior diagnosis of IBD (Crohn's, ulcerative colitis, IBD unclassified, and IBD with cholangitis) between 2005 and 2018 were identified. Descriptive analyses and logistic regression models were used to compare the characteristics of the 2 groups and their outcomes up to 2 years. RESULTS: Three hundred ninety thousand six hundred fourteen patients diagnosed with CRC were included, of whom 5,141 (1.3%) also had a previous diagnosis of IBD. IBD-CRC cases were younger (median age at CRC diagnosis [interquartile range] 66 [54-76] vs 72 [63-79] years [ P < 0.01]), more likely to be diagnosed with CRC as an emergency (25.1% vs 16.7% [ P < 0.01]), and more likely to have a right-sided colonic tumor (37.4% vs 31.5% [ P < 0.01]). Total colectomy was performed in 36.3% of those with IBD (15.4% of Crohn's, 44.1% of ulcerative colitis, 44.5% of IBD unclassified, and 67.7% of IBD with cholangitis). Synchronous (3.2% vs 1.6% P < 0.01) and metachronous tumors (1.7% vs 0.9% P < 0.01) occurred twice as frequently in patients with IBD compared with those without IBD. Stage-specific survival up to 2 years was worse for IBD-associated cancers. DISCUSSION: IBD-associated CRCs occur in younger patients and have worse outcomes than sporadic CRCs. There is an urgent need to find reasons for these differences to inform screening, surveillance, and treatment strategies for CRC and its precursors in this high-risk group.

Differences in the management of patients requiring an emergency resection for colonic cancer in two European populations.

BACKGROUND: Patients with colonic cancer who require emergency colonic cancer surgery often experience poorer outcomes compared with their elective counterparts. In this setting, several treatments approaches are available. In 2009, Danish guidelines recommended treatment with stent for obstruction in left-sided tumours as a bridge to surgery, if expertise is accessible. The aim of this study was to compare the use of elective and emergency resections for colonic cancer and postoperative mortality in two similar demographic populations. METHODS: All patients who underwent a major resection for colonic cancer, between 2005 and 2016 in Denmark and Yorkshire (UK) were identified. The proportion undergoing emergency surgery, the proportion receiving a stent procedure before their resection, and 30-day postoperative mortality were compared between the populations. Logistic regression was used to determine changes in the proportion of those undergoing emergency surgery and 30-day postoperative mortality. RESULTS: Out of 45 397 patients treated during the study interval, 41 880 were selected. Emergency surgery decreased in Denmark from 16.6 per cent in 2005-07 to 12.9 per cent in 2014-16, but increased in Yorkshire (13.5 per cent to 16.8 per cent). Danish patients with left-sided tumours were less likely to undergo emergency surgery (risk ratio 0.90, 95 per cent c.i. 0.82 to 0.99) and an increase in stent use coincided with a statistically significant decrease in emergency surgery in these patients. Thirty-day postoperative mortality in all resections (elective and emergency) decreased in both populations, but a larger decrease was observed in Denmark (7.7 per cent to 3.0 per cent in Denmark and 7.1 per cent to 3.3 per cent in Yorkshire). CONCLUSION: Patients in Denmark experienced a reduction in the use of emergency resection and increase in stenting procedures, following the policy implemented in some departments of converting potential emergency resections into elective resections.

International trends in cancer incidence in middle-aged and older adults in 44 countries.

OBJECTIVE: We examine international incidence trends of lung, colorectal, prostate, and breast cancers, as well as all cancers combined excluding non-melanoma skin cancer (NMSC) in adults aged 50 and older, over a fifteen-year period using data from 113 high quality population-based cancer registries included in the Cancer in Five Continents (CI5) series and NORDCAN. MATERIALS AND METHODS: We calculated annual incidence rates between 1998 and 2012 for ages 50-64, 65-74, and 75+, by sex and both sexes combined. We estimated average annual percentage change (AAPC) in rates using quasi-Poisson regression models. RESULTS: From 1998 to 2012, incidence trends for all cancers (excluding NMSC) have increased in most countries across all age groups, with the greatest increase observed in adults aged 75+ in Ecuador (AAPC = +3%). Colorectal cancer incidence rates increased in the majority of countries, across all age groups. Lung cancer rates among females have increased but decreased for males. Prostate cancer rates have sharply increased in men aged 50-64 with AAPC between 5% and 15% in 24 countries, while decreasing in the 75+ age group in 21 countries, by up to -7% in Bahrain. Female breast cancer rates have increased across all age groups in most countries, especially in the 65-74 age group and in Asia with AAPC increasing to 7% in the Republic of Korea. CONCLUSIONS: These findings assist with anticipating changing patterns and needs internationally. Due to the specific needs of older patients, it is urgent that cancer systems adapt to address their growing number.

Consultations for clinical features of possible cancer and associated urgent referrals before and during the COVID-19 pandemic: an observational cohort study from English primary care.

BACKGROUND: It remains unclear to what extent reductions in urgent referrals for suspected cancer during the COVID-19 pandemic were the result of fewer patients attending primary care compared to GPs referring fewer patients. METHODS: Cohort study including electronic health records data from 8,192,069 patients from 663 English practices. Weekly consultation rates, cumulative consultations and referrals were calculated for 28 clinical features from the NICE suspected cancer guidelines. Clinical feature consultation rate ratios (CRR) and urgent referral rate ratios (RRR) compared time periods in 2020 with 2019. FINDINGS: Consultations for cancer clinical features decreased by 24.19% (95% CI: 24.04-24.34%) between 2019 and 2020, particularly in the 6-12 weeks following the first national lockdown. Urgent referrals for clinical features decreased by 10.47% (95% CI: 9.82-11.12%) between 2019 and 2020. Overall, once patients consulted with primary care, GPs urgently referred a similar or greater proportion of patients compared to previous years. CONCLUSION: Due to the significant fall in patients consulting with clinical features of cancer there was a lower than expected number of urgent referrals in 2020. Sustained efforts should be made throughout the pandemic to encourage the public to consult their GP with cancer clinical features.

Influence of age on surgical treatment and postoperative outcomes of patients with colorectal cancer in Denmark and Yorkshire, England.

AIM: Denmark and Yorkshire are demographically similar and both have undergone changes in their management of colorectal cancer to improve outcomes. The differential provision of surgical treatment, especially in the older age groups, may contribute to the magnitude of improved survival rates. This study aimed to identify differences in the management of colorectal cancer surgery and postoperative outcomes according to patient age between Denmark and Yorkshire. METHOD: This was a retrospective population-based study of colorectal cancer patients diagnosed in Denmark and Yorkshire between 2005 and 2016. Proportions of patients undergoing major surgical resection, postoperative mortality and relative survival were compared between Denmark and Yorkshire across several age groups (18-59, 60-69, 70-79 and ≥80 years) and over time. RESULTS: The use of major surgical resection was higher in Denmark than in Yorkshire, especially for patients aged ≥80 years (70.5% versus 50.5% for colon cancer, 49.3% versus 38.1% for rectal cancer). Thirty-day postoperative mortality for Danish patients aged ≥80 years was significantly higher than that for Yorkshire patients with colonic cancer [OR (95% CI) = 1.22 (1.07, 1.38)] but not for rectal cancer or for 1-year postoperative mortality. Relative survival significantly increased in all patients aged ≥80 years except for Yorkshire patients with colonic cancer. CONCLUSION: This study suggests that there are major differences between the management of elderly patients with colorectal cancer between the two populations. Improved selection for surgery and better peri- and postoperative care in these patients appears to improve long-term outcomes, but may come at the cost of a higher 30-day mortality.

Health economic studies of colorectal cancer and the contribution of administrative data: A systematic review.

INTRODUCTION: Several forces are contributing to an increase in the number of people living with and surviving colorectal cancer (CRC). However, due to the lack of available data, little is known about the implications of these forces. In recent years, the use of administrative records to inform research has been increasing. The aim of this paper is to investigate the potential contribution that administrative data could have on the health economic research of CRC. METHODS: To achieve this aim, we conducted a systematic review of the health economic CRC literature published in the United Kingdom and Europe within the last decade (2009-2019). RESULTS: Thirty-seven relevant studies were identified and divided into economic evaluations, cost of illness studies and cost consequence analyses. CONCLUSIONS: The use of administrative data, including cancer registry, screening and hospital records, within the health economic research of CRC is commonplace. However, we found that this data often come from regional databases, which reduces the generalisability of results. Further, administrative data appear less able to contribute towards understanding the wider and indirect costs associated with the disease. We explore several ways in which various sources of administrative data could enhance future research in this area.

The impact of timely cancer diagnosis on age disparities in colon cancer survival.

OBJECTIVE: We described the role of patient-related and clinical factors on age disparities in colon cancer survival among patients aged 50-99 using New Zealand population-based cancer registry data linked to hospitalisation data. METHOD: We included 21,270 new colon cancer cases diagnosed between 1 January 2006 and 31 July 2017, followed up to end 2019. We modelled the effect of age at diagnosis, sex, ethnicity, deprivation, comorbidity, and emergency presentation on colon cancer survival by stage at diagnosis using flexible excess hazard regression models. RESULTS: The excess mortality in older patients was minimal for localised cancers, maximal during the first six months for regional cancers, the first eighteen months for distant cancers, and over the three years for missing stages. The age pattern of the excess mortality hazard varied according to sex for distant cancers, emergency presentation for regional and distant cancers, and comorbidity for cancer with missing stages. Ethnicity and deprivation did not influence age disparities in colon cancer survival. CONCLUSION: Factors reflecting timeliness of cancer diagnosis most affected age-related disparities in colon cancer survival, probably by impacting treatment strategy. Because of the high risk of poor outcomes related to treatment in older patients, efforts made to improve earlier diagnosis in older patients are likely to help reduce age disparities in colon cancer survival in New Zealand.

Microbiome Analysis of More Than 2,000 NHS Bowel Cancer Screening Programme Samples Shows the Potential to Improve Screening Accuracy.

PURPOSE: There is potential for fecal microbiome profiling to improve colorectal cancer screening. This has been demonstrated by research studies, but it has not been quantified at scale using samples collected and processed routinely by a national screening program. EXPERIMENTAL DESIGN: Between 2016 and 2019, the largest of the NHS Bowel Cancer Screening Programme hubs prospectively collected processed guaiac fecal occult blood test (gFOBT) samples with subsequent colonoscopy outcomes: blood-negative [n = 491 (22%)]; colorectal cancer [n = 430 (19%)]; adenoma [n = 665 (30%)]; colonoscopy-normal [n = 300 (13%)]; nonneoplastic [n = 366 (16%)]. Samples were transported and stored at room temperature. DNA underwent 16S rRNA gene V4 amplicon sequencing. Taxonomic profiling was performed to provide features for classification via random forests (RF). RESULTS: Samples provided 16S amplicon-based microbial profiles, which confirmed previously described colorectal cancer-microbiome associations. Microbiome-based RF models showed potential as a first-tier screen, distinguishing colorectal cancer or neoplasm (colorectal cancer or adenoma) from blood-negative with AUC 0.86 (0.82-0.89) and AUC 0.78 (0.74-0.82), respectively. Microbiome-based models also showed potential as a second-tier screen, distinguishing from among gFOBT blood-positive samples, colorectal cancer or neoplasm from colonoscopy-normal with AUC 0.79 (0.74-0.83) and AUC 0.73 (0.68-0.77), respectively. Models remained robust when restricted to 15 taxa, and performed similarly during external validation with metagenomic datasets. CONCLUSIONS: Microbiome features can be assessed using gFOBT samples collected and processed routinely by a national colorectal cancer screening program to improve accuracy as a first- or second-tier screen. The models required as few as 15 taxa, raising the potential of an inexpensive qPCR test. This could reduce the number of colonoscopies in countries that use fecal occult blood test screening.

Impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England: a population-based study.

BACKGROUND: There are concerns that the COVID-19 pandemic has had a negative effect on cancer care but there is little direct evidence to quantify any effect. This study aims to investigate the impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England. METHODS: Data were extracted from four population-based datasets spanning NHS England (the National Cancer Cancer Waiting Time Monitoring, Monthly Diagnostic, Secondary Uses Service Admitted Patient Care and the National Radiotherapy datasets) for all referrals, colonoscopies, surgical procedures, and courses of rectal radiotherapy from Jan 1, 2019, to Oct 31, 2020, related to colorectal cancer in England. Differences in patterns of care were investigated between 2019 and 2020. Percentage reductions in monthly numbers and proportions were calculated. FINDINGS: As compared to the monthly average in 2019, in April, 2020, there was a 63% (95% CI 53-71) reduction (from 36 274 to 13 440) in the monthly number of 2-week referrals for suspected cancer and a 92% (95% CI 89-95) reduction in the number of colonoscopies (from 46 441 to 3484). Numbers had just recovered by October, 2020. This resulted in a 22% (95% CI 8-34) relative reduction in the number of cases referred for treatment (from a monthly average of 2781 in 2019 to 2158 referrals in April, 2020). By October, 2020, the monthly rate had returned to 2019 levels but did not exceed it, suggesting that, from April to October, 2020, over 3500 fewer people had been diagnosed and treated for colorectal cancer in England than would have been expected. There was also a 31% (95% CI 19-42) relative reduction in the numbers receiving surgery in April, 2020, and a lower proportion of laparoscopic and a greater proportion of stoma-forming procedures, relative to the monthly average in 2019. By October, 2020, laparoscopic surgery and stoma rates were similar to 2019 levels. For rectal cancer, there was a 44% (95% CI 17-76) relative increase in the use of neoadjuvant radiotherapy in April, 2020, relative to the monthly average in 2019, due to greater use of short-course regimens. Although in June, 2020, there was a drop in the use of short-course regimens, rates remained above 2019 levels until October, 2020. INTERPRETATION: The COVID-19 pandemic has led to a sustained reduction in the number of people referred, diagnosed, and treated for colorectal cancer. By October, 2020, achievement of care pathway targets had returned to 2019 levels, albeit with smaller volumes of patients and with modifications to usual practice. As pressure grows in the NHS due to the second wave of COVID-19, urgent action is needed to address the growing burden of undetected and untreated colorectal cancer in England. FUNDING: Cancer Research UK, the Medical Research Council, Public Health England, Health Data Research UK, NHS Digital, and the National Institute for Health Research Oxford Biomedical Research Centre.

National variation in pulmonary metastasectomy for colorectal cancer.

AIM: Evidence on patterns of use of pulmonary metastasectomy in colorectal cancer patients is limited. This population-based study aims to investigate the use of pulmonary metastasectomy in the colorectal cancer population across the English National Health Service (NHS) and quantify the extent of any variations in practice and outcome. METHODS: All adults who underwent a major resection for colorectal cancer in an NHS hospital between 2005 and 2013 were identified in the COloRECTal cancer data Repository (CORECT-R). All inpatient episodes corresponding to pulmonary metastasectomy, occurring within 3 years of the initial colorectal resection, were identified. Multi-level logistic regression was used to determine patient and organizational factors associated with the use of pulmonary metastasectomy for colorectal cancer, and Kaplan-Meier and Cox models were used to assess survival following pulmonary metastasectomy. RESULTS: In all, 173 354 individuals had a major colorectal resection over the study period, with 3434 (2.0%) undergoing pulmonary resection within 3 years. The frequency of pulmonary metastasectomy increased from 1.2% of patients undergoing major colorectal resection in 2005 to 2.3% in 2013. Significant variation was observed across hospital providers in the risk-adjusted rates of pulmonary metastasectomy (0.0%-6.8% of patients). Overall 5-year survival following pulmonary resection was 50.8%, with 30-day and 90-day mortality of 0.6% and 1.2% respectively. CONCLUSIONS: This study shows significant variation in the rates of pulmonary metastasectomy for colorectal cancer across the English NHS.