Transforming post pandemic cancer services.

This paper outlines the impact of the COVID-19 pandemic on cancer services in the UK including screening, symptomatic diagnosis, treatment pathways and projections on clinical outcomes as a result of these care disruptions. A restoration of cancer services to pre-pandemic levels is not likely to mitigate this adverse impact, particularly with an ageing population and increased cancer burden. New cancer cases are projected to rise to over 500,000 per year by 2035, with over 4 million people living with and beyond cancer. This paper calls for a strategic transformation to prioritise effort on the basis of available datasets and evidence-in particular, to prioritise cancers where an earlier diagnosis is feasible and clinically useful with a focus on mortality benefit by preventing emergency presentations by harnessing data and analytics. This could be delivered by a focus on underperforming groups/areas to try and reduce inequity, linking near real-time datasets with clinical decision support systems at the primary and secondary care levels, promoting the use of novel technologies to improve patient uptake of services, screening and diagnosis, and finally, upskilling and cross-skilling healthcare workers to expand supply of diagnostic and screening services.

Future cancer risk after urgent suspected cancer referral in England when cancer is not found: a national cohort study.

BACKGROUND: Following referral for investigation of urgent suspected cancer within the English National Health Service referral system, 7% of referred individuals are diagnosed with cancer. This study aimed to investigate the risk of cancer occurrence within 1-5 years of finding no cancer following an urgent suspected cancer referral. METHODS: This national cohort study used urgent suspected cancer referral data for England from the Cancer Waiting Times dataset and linked it with cancer diagnosis data from the National Cancer Registration dataset. Data were extracted for the eight most commonly referred to urgent suspected cancer referral pathways (breast, gynaecological, head and neck, lower and upper gastrointestinal, lung, skin, and urological) for the period April 1, 2013, to March 31, 2014, with 5-year follow-up for individuals with no cancer diagnosis within 1 year of referral. The primary objective was to investigate the occurrence and type of subsequent cancer in years 1-5 following an urgent suspected cancer referral when no cancer was initially found, both overall and for each of the eight referral pathways. The numbers of subsequent cancers were compared with expected cancer incidence in years 1-5 following referral, using standardised incidence ratios (SIRs) based on matched age-gender distributions of expected cancer incidence in England for the same time period. The analysis was repeated, stratifying by referral group, and by calculating the absolute and expected rate of all cancers and of the same individual cancer as the initial referral. FINDINGS: Among 1·18 million referrals without a cancer diagnosis in years 0-1, there were 63 112 subsequent cancers diagnosed 1-5 years post-referral, giving an absolute rate of 1338 (95% CI 1327-1348) cancers per 100 000 referrals per year (1038 [1027-1050] in females, 1888 [1867-1909] in males), compared with an expected rate of 1054 (1045-1064) cancers per 100 000 referrals per year (SIR 1·27 [95% CI 1·26-1·28]). The absolute rate of any subsequent cancer diagnosis 1-5 years after referral was lowest following suspected breast cancer referral (746 [728-763] cancers per 100 000 referrals per year) and highest following suspected urological (2110 [2070-2150]) or lung cancer (1835 [1767-1906]) referral. For diagnosis of the same cancer as the initial referral pathway, the highest absolute rates were for the urological and lung pathways (1011 [984-1039] and 638 [598-680] cancers per 100 000 referrals per year, respectively). The highest relative risks of subsequent diagnosis of the same cancer as the initial referral pathway were for the head and neck pathway (SIR 3·49 [95% CI 3·22-3·78]) and lung pathway (3·00 [2·82-3·20]). INTERPRETATION: Cancer risk was higher than expected in the 5 years following an urgent suspected cancer referral. The potential for targeted interventions, such as proactive monitoring, safety-netting, and cancer awareness or risk reduction initiatives should be investigated. FUNDING: Cancer Research UK.

Association between time-to-treatment and outcomes in non-small cell lung cancer: a systematic review.

BACKGROUND: National targets for timely diagnosis and management of a potential cancer are driven in part by the perceived risk of disease progression during avoidable delays. However, it is unclear to what extent time-to-treatment impacts prognosis for patients with non-small cell lung cancer, with previous reviews reporting mixed or apparently paradoxical associations. This systematic review focuses on potential confounders in order to identify particular patient groups which may benefit most from timely delivery of care. METHODS: Medline, EMBASE and Cochrane databases were searched for publications between January 2012 and October 2020, correlating timeliness in secondary care pathways to patient outcomes. The protocol is registered with PROSPERO (the International Prospective Register of Systematic Reviews; ID 99239). Prespecified factors (demographics, performance status, histology, stage and treatment) are examined through narrative synthesis. RESULTS: Thirty-seven articles were included. All but two were observational. Timely care was generally associated with a worse prognosis in those with advanced stage disease (6/8 studies) but with better outcomes for patients with early-stage disease treated surgically (9/12 studies). In one study, patients with squamous cell carcinoma referred for stereotactic ablative radiotherapy benefited more from timely care, compared with patients with adenocarcinoma. One randomised controlled trial supported timeliness as being advantageous in those with stage I-IIIA disease. CONCLUSION: There are limitations to the available evidence, but observed trends suggest timeliness to be of particular importance in surgical candidates. In more advanced disease, survival trends are likely outweighed by symptom burden, performance status or clinical urgency dictating timeliness of treatment.

COVID-19 and the multidisciplinary care of patients with lung cancer: an evidence-based review and commentary.

Delivering lung cancer care during the COVID-19 pandemic has posed significant and ongoing challenges. There is a lack of published COVID-19 and lung cancer evidence-based reviews, including for the whole patient pathway. We searched for COVID-19 and lung cancer publications and brought together a multidisciplinary group of stakeholders to review and comment on the evidence and challenges. A rapid review of the literature was undertaken up to 28 October 2020, producing 144 papers, with 113 full texts screened. We focused on new primary data collection (qualitative or quantitative evidence) and excluded case reports, editorials and commentaries. Following exclusions, 15 published papers were included in the review and are summarised. They included one qualitative paper and 14 quantitative studies (surveys or cohort studies), with a total of 2295 lung cancer patients data included (mean study size 153 patients; range 7-803). Review of current evidence and commentary included awareness and help-seeking; lung cancer screening; primary care assessment and referral; diagnosis and treatment in secondary care, including oncology and surgery; patient experience and palliative care. Cross-cutting themes and challenges were identified using qualitative methods for patients, healthcare professionals and service delivery, with a clear need for continued studies to guide evidence-based decision-making.

Geographical variations in the use of cancer treatments are associated with survival of lung cancer patients.

INTRODUCTION: Lung cancer outcomes in England are inferior to comparable countries. Patient or disease characteristics, healthcare-seeking behaviour, diagnostic pathways, and oncology service provision may contribute. We aimed to quantify associations between geographic variations in treatment and survival of patients in England. METHODS: We retrieved detailed cancer registration data to analyse the variation in survival of 176,225 lung cancer patients, diagnosed 2010-2014. We used Kaplan-Meier analysis and Cox proportional hazards regression to investigate survival in the two-year period following diagnosis. RESULTS: Survival improved over the period studied. The use of active treatment varied between geographical areas, with inter-quintile ranges of 9%-17% for surgical resection, 4%-13% for radical radiotherapy, and 22%-35% for chemotherapy. At 2 years, there were 188 potentially avoidable deaths annually for surgical resection, and 373 for radical radiotherapy, if all treated proportions were the same as in the highest quintiles. At the 6 month time-point, 318 deaths per year could be postponed if chemotherapy use for all patients was as in the highest quintile. The results were robust to statistical adjustments for age, sex, socio-economic status, performance status and co-morbidity. CONCLUSION: The extent of use of different treatment modalities varies between geographical areas in England. These variations are not attributable to measurable patient and tumour characteristics, and more likely reflect differences in clinical management between local multi-disciplinary teams. The data suggest improvement over time, but there is potential for further survival gains if the use of active treatments in all areas could be increased towards the highest current regional rates.

Attitudes to participating in a birth cohort study, views from a multiethnic population: a qualitative study using focus groups.

BACKGROUND: Recruitment to birth cohort studies is a challenge. Few studies have addressed the attitudes of women about taking part in birth cohort studies particularly those from ethnic minority groups. OBJECTIVE: To seek the views of people from diverse ethnic backgrounds about participation in a proposed birth cohort examining the impact of infections. DESIGN AND SETTING: Eight focus groups of pregnant women and mothers of young children took place in GP surgeries and community centres in an ethnically diverse area of east London. Purposeful sampling and language support ensured representation of people from ethnic minority groups. Audio recordings were taken and transcripts were analysed using the Framework approach. MAIN OUTCOME MEASURES: The views of participants about taking part in the proposed birth cohort study, in particular concerning incentives to taking part, disincentives and attitudes to consenting children. RESULTS: There was more convergence of opinion than divergence across groups. Altruism, perceived health gains of participating and financial rewards were motivating factors for most women. Worries about causing harm to their child, inconvenience, time pressure and blood sample taking as well as a perceived lack of health gains were disincentives to most. Mistrust of researchers did not appear to be a significant barrier. The study indicates that ethnicity and other demographic factors influence attitudes to participation. CONCLUSIONS: To recruit better, birth cohort studies should incorporate financial and health gains as rewards for participation, promote the altruistic goals of research, give assurances regarding the safety of the participating children and sensitive data, avoid discomfort and maximize convenience. Ethnicity influences attitudes to participation in many ways, and researchers should explore these factors in their target population.

Primary care and cancer: Facing the challenge of early diagnosis and survivorship.

With ageing populations and an increasing lifetime risk of cancer, primary care will continue to play an increasingly important role in early diagnosis and cancer survivorship, especially with the lowering of risk thresholds for referral and diagnostic investigations. However, primary care in many countries is in crisis with increasing workloads for primary care physicians. Potential solutions to these challenges will be outlined including development of multidisciplinary teams, diagnostic decision support, increasing access to diagnostics and cost-effective referral pathways.

Carbon in airway macrophages from children with asthma.

BACKGROUND: Airway macrophage (AM) phagocytosis is impaired in severe asthma. Prostaglandin (PG) E2 and D2 are increased in severe asthma and suppress AM phagocytic function in vitro. In this study, we sought evidence for PG-mediated impairment of phagocytosis of inhalable carbonaceous particulate matter (PM) by AM in children with severe asthma compared with mild asthmatics and healthy controls. METHODS: AM were obtained from children with asthma and healthy controls using induced sputum. AM carbon area (µm(2)) was assessed by image analysis. In a subgroup of asthmatics, urinary PGE2 and PGD2 metabolites were measured by high-performance liquid chromatography, and PM exposure at the home address was modelled. Phagocytosis of PM by human monocyte-derived macrophages and rat AM was assessed in vitro by image analysis. RESULTS: AM carbon was 51% lower in children with moderate-to-severe asthma (n=36) compared with mild asthmatics (n=12, p<0.01) and healthy controls (n=47, p<0.01). There was no association between modelled PM exposure and AM carbon in 33 asthmatics who had a urine sample, but there was an inverse association between AM carbon and urinary metabolites of PGE2 and D2 (n=33, rs=-0.40, p<0.05, and rs=-0.44, p<0.01). PGE2 10(-6) M, but not PGD2 10(-6) M, suppressed phagocytosis of PM10 by human macrophages in vitro (p<0.05 vs control). PGE2 10(-6) M also suppressed phagocytosis of PM10 by rat AM in vitro (p<0.01 vs control). CONCLUSIONS: Phagocytosis of inhaled carbonaceous PM by AMs is impaired in severe asthma. PGE2 may contribute to impaired AM phagocytic function in severe asthma.

Advice after urgent suspected cancer referral when cancer is not found in England: Survey of patients' preferences and perceived acceptability.

Objective: No standardised approach exists to provide advice after urgent suspected cancer (USC) referral when cancer is not found. This study aimed to assess preferences and acceptability of receiving advice after USC referral related to: 1) managing ongoing symptoms, 2) responding to early symptoms of other cancers, 3) cancer screening, 4) reducing risks of future cancer. Methods: 2,541 patients from two English NHS Trusts were mailed a survey 1-3 months after having no cancer found following urgent suspected gastrointestinal or head and neck cancer referral. Participants were asked about: willingness to receive advice; prospective acceptability; preferences related to mode, timing and who should provide advice; and previous advice receipt. Results: 406 patients responded (16.0%) with 397 in the final analyses. Few participants had previously received advice, yet most were willing to. Willingness varied by type of advice: fewer were willing to receive advice about early symptoms of other cancers (88.9%) than advice related to ongoing symptoms (94.3%). Acceptability was relatively high for all advice types. Reducing the risk of future cancer advice was more acceptable. Acceptability was lower in those from ethnic minority groups, and with lower levels of education. Most participants preferred to receive advice from a doctor; with results or soon after; either face to face or via the telephone. Conclusions: There is a potential unmet need for advice after USC referral when no cancer is found. Equitable intervention design should focus on increasing acceptability for people from ethnic minority groups and those with lower levels of education.

Should we? Could we? Feasibility of interventions to support prevention or early diagnosis of future cancer following urgent referral: A qualitative study.

OBJECTIVE: This study investigated perspectives of healthcare professionals (HCPs) on the feasibility of giving additional support to patients after cancer is not found following urgent referral. We sought to understand key facilitators or barriers to offering such support. METHODS: A convenience sample of primary and secondary care healthcare professionals (n = 36) participated in semi-structured interviews. Interviews were transcribed verbatim and analysed using Framework Analysis, inductively and deductively, guided by the Theoretical Domains Framework. RESULTS: HCPs indicated that support should be offered if proven to be efficacious. It needs to avoid potential negative consequences such as patient anxiety and information overload. HCPs were more hesitant about whether support could feasibly be offered, due to resource restrictions and perceived remit of the urgent pathway for suspected cancer. CONCLUSION: HCP support after discharge from urgent cancer referral pathways needs to be resource efficient, developed in collaboration with patients and should have proven efficacy. Development of brief interventions for delivery by a range of staff, and use of technology could mitigate barriers to implementation. PRACTICE IMPLICATIONS: Changes to discharge procedures to provide information, endorsement or direction to services could offer much needed support. Additional support would need to overcome logistical challenges and address limited capacity.

Associations between general practice characteristics and chest X-ray rate: an observational study.

BACKGROUND: Chest X-ray (CXR) is the first-line test for lung cancer in many settings. Previous research has suggested that higher utilisation of CXR is associated with improved outcomes. AIM: To explore the associations between characteristics of general practices and frequency of investigation with CXR. DESIGN AND SETTING: Retrospective observational study of English general practices. METHOD: A database was constructed of English general practices containing number of CXRs requested and data on practices for 2018, including patient and staff demographics, smoking prevalence, deprivation, and patient satisfaction indicators. Mixed-effects Poisson modelling was used to account for variation because of chance and to estimate the amount of remaining variation that could be attributed to practice and population characteristics. RESULTS: There was substantial variation in GP CXR rates (median 34 per 1000 patients, interquartile range 26-43). Only 18% of between-practice variance in CXR rate was accounted for by recorded characteristics. Higher practice scores for continuity and communication skills, and higher proportions of smokers, Asian and mixed ethnic groups, and patients aged >65 years were associated with increased CXR rates. Higher patient satisfaction scores for access and greater proportions of male patients and patients of Black ethnicity were associated with lower CXR rates. CONCLUSION: Substantial variation was found in CXR rates beyond that expected by chance, which could not be accounted for by practices' recorded characteristics. As other research has indicated that increasing CXR rates can lead to earlier detection, supporting practices that currently investigate infrequently could be an effective strategy to improve lung cancer outcomes.

Non-speculum sampling approaches for cervical screening in older women: randomised controlled trial.

BACKGROUND: Cervical cancer disproportionately affects women ≥65 years, especially those not screened regularly. Speculum use is a key barrier. AIM: To assess if offering non-speculum clinician-taken sampling and self-sampling increases uptake for lapsed attenders aged 50-64 years. DESIGN AND SETTING: Pragmatic randomised control trial conducted at 10 general practices in East London, UK. METHOD: Participants were 784 women aged 50-64 years, last screened 6-15 years before randomisation. Intervention participants received a letter offering the choice of non-speculum clinician- or self-sampling. Control participants received usual care. The main outcome measure was uptake within 4 months. RESULTS: Screening uptake 4 months after randomisation was significantly higher in the intervention arm: 20.4% (n = 80/393) versus 4.9% in the control arm (n = 19/391, absolute difference 15.5%, 95% confidence interval [CI] = 11.0% to 20.0%, P<0.001). This was maintained at 12 months: intervention 30.5% (n = 120/393) versus control 13.6% (n = 53/391) (absolute difference 17.0%, 95% CI = 11.3% to 22.7%, P<0.001). Conventional screening attendance within 12 months was very similar for both intervention 12.7% (n = 50/393) and control 13.6% (n = 53/391) arms. Ethnic differences were seen in screening modality preference. More White women opted for self-sampling (50.7%, n = 38/75), whereas most Asian and Black women and those from other ethnic backgrounds opted for conventional screening. CONCLUSION: Offering non-speculum clinician-taken sampling and self-sampling substantially increases uptake in older lapsed attendee women. Non-speculum clinician sampling appeals to women who dislike the speculum but still prefer a clinician to take their sample. Providing a choice of screening modality may be important for optimising cervical screening uptake.

Non-speculum clinician-taken samples for human papillomavirus testing: a cross-sectional study in older women.

BACKGROUND: Cervical cancer incidence and mortality are high in women aged ≥65 years, despite the disease being preventable by screening. Speculum-based screening can become more uncomfortable after the menopause. AIM: To examine test performance and acceptability of human papillomavirus (HPV) testing on clinician-collected vaginal samples without a speculum (non-speculum). DESIGN AND SETTING: Cross-sectional study in 11 GP practices and four colposcopy clinics in London, UK, between August 2017 and January 2019. METHOD: Non-speculum and conventional (speculum) samples were collected from women aged ≥50 years attending for a colposcopy (following a speculum HPV-positive screening result) or women aged ≥35 years (with confirmed cervical intraepithelial neoplasia (CIN) 2+), and women aged 50-64 years attending routine screening. Sensitivity to CIN2+ was assessed among women with confirmed CIN2+ (colposcopy). Specificity to HPV relative to speculum sampling and overall concordance was assessed among women with negative cytology (routine screening). RESULTS: The sensitivity of non-speculum sampling for detecting CIN2+ was 83.3% (95% confidence interval [CI] = 60.8 to 94.2) (n = 15/18). There was complete concordance among women with positive CIN2+ who had a speculum sample ≤91 days prior to the non-speculum sample (n = 12). Among 204 women with negative cytology, the specificity to HPV was 96.4% (95% CI = 92.7 to 98.5), with 96.6% concordant results (κ 72.4%). Seventy-one percent (n = 120/170) of women preferred a non-speculum sample for their next screen. CONCLUSION: HPV testing on non-speculum clinician-taken samples is a viable approach that warrants further exploration in larger studies. Overall test performance was broadly comparable with that of self-sampling.

Cancer detection via primary care urgent referral and association with practice characteristics: a retrospective cross-sectional study in England from 2009/2010 to 2018/2019.

BACKGROUND: There is substantial variation in the use of urgent suspected cancer referral (2-week wait [2WW]) between practices. AIM: To examine the change in use of 2WW referrals in England over 10 years (2009/2010 to 2018/2019) and the practice and population factors associated with cancer detection. DESIGN AND SETTING: Retrospective cross-sectional study of English general practices and their 2WW referral and Cancer Waiting Times database detection data (all cancers other than non-melanoma skin cancers) from 2009/2010 to 2018/2019. METHOD: A retrospective study conducted using descriptive statistics of changes over 10 years in 2WW referral data. Yearly linear regression models were used to determine the association between cancer detection rates and quintiles of practice and population characteristics. Predicted cancer detection rates were calculated, as well as the difference between lowest to highest quintiles. RESULTS: Over the 10 years studied there were 14.89 million 2WW referrals (2.24 million in 2018/2019), and 2.68 million new cancer diagnoses, of which 1.26 million were detected following 2WW. The detection rate increased from 41% to 52% over the time period. In 2018/2019 an additional 66 172 cancers were detected via 2WW compared with 2009/2010. Higher cancer detection via 2WW referrals was associated with larger practices and those with younger GPs. From 2016/2017 onwards more deprived practice populations were associated with decreased cancer detection. CONCLUSION: From 2009/2010 to 2018/2019 2WW referrals increased on average by 10% year on year. The most consistent association with higher cancer detection was found for larger practices and those with younger GPs, though these differences became attenuated over time. The more recent association between increased practice deprivation and lower cancer detection is a cause for concern. The COVID-19 pandemic has led to significant impacts on 2WW referral activity and the impact on patient outcomes will need to be studied.

Association between use of urgent suspected cancer referral and mortality and stage at diagnosis: a 5-year national cohort study.

BACKGROUND: There is considerable variation between GP practices in England in their use of urgent referral pathways for suspected cancer. AIM: To determine the association between practice use of urgent referral and cancer stage at diagnosis and cancer patient mortality, for all cancers and the most common types of cancer (colorectal, lung, breast, and prostate). DESIGN AND SETTING: National cohort study of 1.4 million patients diagnosed with cancer in England between 2011 and 2015. METHOD: The cohort was stratified according to quintiles of urgent referral metrics. Cox proportional hazards regression was used to quantify risk of death, and logistic regression to calculate odds of late-stage (III/IV) versus early-stage (I/II) cancers in relation to referral quintiles and cancer type. RESULTS: Cancer patients from the highest referring practices had a lower hazard of death (hazard ratio [HR] = 0.96; 95% confidence interval [CI] = 0.95 to 0.97), with similar patterns for individual cancers: colorectal (HR = 0.95; CI = 0.93 to 0.97); lung (HR = 0.95; CI = 0.94 to 0.97); breast (HR = 0.96; CI = 0.93 to 0.99); and prostate (HR = 0.88; CI = 0.85 to 0.91). Similarly, for cancer patients from these practices, there were lower odds of late-stage diagnosis for individual cancer types, except for colorectal cancer. CONCLUSION: Higher practice use of referrals for suspected cancer is associated with lower mortality for the four most common types of cancer. A significant proportion of the observed mortality reduction is likely due to earlier stage at diagnosis, except for colorectal cancer. This adds to evidence supporting the lowering of referral thresholds and consequent increased use of urgent referral for suspected cancer.