Colorectal cancer outcomes determined by mode of presentation: analysis of population data in England between 2010 and 2014.

BACKGROUND: The purpose of this study was to investigate associations between mode of presentation; categorized as emergency, suspected cancer outpatient referral pathway (2-week wait or 2WW pathway), non-cancer suspected outpatient referral (non-2-week wait pathway) or following screening, and stage of diagnosis and survival in patients with colorectal cancer in England. METHODS: This was a retrospective cohort observational study of patients diagnosed with colorectal cancer between January 2010 and December 2014 in England using data from Public Health England collated from regional cancer registries. RESULTS: The most common route to diagnosis among 167,501 patients diagnosed with colorectal cancer was via the non-cancer suspect (non-2WW) outpatient referral pathway (35.1%) followed by the suspected cancer (2WW) referral pathway (31.6%), emergency presentation (22.8%) and most infrequently following screening (10.6%) (p < 0.01). Screening confers the greatest likelihood of early-stage diagnosis (61.6%) compared to other modes of presentation. The 5-year overall survival was 81.8%, 53.3%, 53.0% and 27.6% in those diagnosed via screening, 2WW, non-2WW pathway and emergency presentation, respectively. Patients from most deprived regions were more likely to be diagnosed following emergency presentation (27.7 vs 19.7%, p < 0.01) and less likely via screening (8.1 vs 12%, p < 0.01). CONCLUSIONS: Asymptomatic individuals diagnosed following screening have earlier stage cancers and better survival, the opposite was observed in those diagnosed following emergency presentation. Patients referred via the 2WW pathway do not have better survival outcomes when compared to those referred via the non-2WW pathway. In addition, this study has identified socio-economic groups that need to be targeted with public health campaigns to improve screening uptake.

Ovarian cancer symptoms, routes to diagnosis and survival - Population cohort study in the 'no screen' arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

OBJECTIVE: There are widespread efforts to increase symptom awareness of 'pelvic/abdominal pain, increased abdominal size/bloating, difficulty eating/feeling full and urinary frequency/urgency' in an attempt to diagnose ovarian cancer earlier. Long-term survival of women with these symptoms adjusted for known prognostic factors is yet to be determined. This study explored the association of symptoms, routes and interval to diagnosis and long-term survival in a population-based cohort of postmenopausal women diagnosed with invasive epithelial tubo-ovarian cancer (iEOC) in the 'no screen' (control) UKCTOCS arm. METHODS: Of 101,299 women in the control arm, 574 were confirmed on outcome review to have iEOC between randomisation (2001-2005) and 31 December 2014. Data was extracted from medical notes and electronic records. A multivariable model was fitted for individual symptoms, time interval from symptom onset to diagnosis, route to diagnosis, speciality, morphological Type, age at diagnosis, year of diagnosis (period effect), stage, primary treatment, and residual disease. RESULTS: Women presenting with symptoms listed in the NICE guidelines (HR1.48, 95%CI1.16-1.89, p = 0.001) or the modified Goff Index (HR1·68, 95%CI1·32-2.13, p < 0.0001) had significantly worse survival than those who did not. Each additional presenting symptom decreased survival (HR1·20, 95%CI1·12-1·28, p < 0.0001). In multivariable analysis, in addition to advanced stage, increasing residual disease and inadequate primary treatment, abdominal pain and loss of appetite/feeling full were significantly associated with increased mortality. CONCLUSIONS: The ovarian cancer symptom indices identify postmenopausal women with a poorer prognosis. This study however cannot exclude the possibility of better outcomes in those who are aware and act on their symptoms.

Achieving a timely diagnosis for teenagers and young adults with cancer: the ACE "too young to get cancer?" study.

BACKGROUND: Time to diagnosis (TTD) concerns teenagers and young adults (TYA) with cancer and may affect outcome. METHODS: Healthcare records from 105 TYA in a regional cancer service were assessed to document events from 1st symptom to treatment start. Detailed pathway construction was possible for 104 patients and allowed a multidisciplinary panel review of each pathway with assessment of good practice and lessons for the future. RESULTS: 1st presentation was to primary care in 86, and 93% consulted in primary care before diagnosis. Routes to Diagnosis were 45% via urgent 2 Week Wait pathways and 38% as emergency referrals. Total Interval (time from 1st presentation to treatment start) was median 63 (range 1-559) days, varying within/between diagnoses. Patient interval (time from 1st symptom to 1st presentation) was longest for lymphoma, carcinoma and bone tumour (medians: 9, 12, 20 days). Overall, time in primary care was short (median 3, range 0-537 days) compared to secondary care (median 29, range 0-195 days) and longest for lymphoma, carcinoma, brain/CNS (medians: 10, 15, 16 days). Specialist Care interval (time from 1st specialist visit to treatment start) was longest for bone, brain/CNS, lymphoma, carcinoma (medians: 30, 33, 36, 48 days). 40% pathways were rated as showing good/best practice but 16% were less than satisfactory. Continued safety-netting/support was identified from primary care but analysis suggested opportunities for improvement in transition through secondary care. CONCLUSIONS: Previous reports of prolonged TTD have focused on delay in referral from primary care but this study suggests that this might be reduced by optimising management in secondary care.

A review of sex-related differences in colorectal cancer incidence, screening uptake, routes to diagnosis, cancer stage and survival in the UK.

BACKGROUND: Colorectal cancer (CRC) is an illness strongly influenced by sex and gender, with mortality rates in males significantly higher than females. There is still a dearth of understanding on where sex differences exist along the pathway from presentation to survival. The aim of this review is to identify where actions are needed to improve outcomes for both sexes, and to narrow the gap for CRC. METHODS: A cross-sectional review of national data was undertaken to identify sex differences in incidence, screening uptake, route to diagnosis, cancer stage at diagnosis and survival, and their influence in the sex differences in mortality. RESULTS: Overall incidence is higher in men, with an earlier age distribution, however, important sex differences exist in anatomical site. There were relatively small differences in screening uptake, route to diagnosis, cancer staging at diagnosis and survival. Screening uptake is higher in women under 69 years. Women are more likely to present as emergency cases, with more men diagnosed through screening and two-week-wait. No sex differences are seen in diagnosis for more advanced disease. Overall, age-standardised 5-year survival is similar between the sexes. CONCLUSIONS: As there are minimal sex differences in the data from routes to diagnosis to survival, the higher mortality of colorectal cancer in men appears to be a result of exogenous and/or endogenous factors pre-diagnosis that lead to higher incidence rates. There are however, sex and gender differences that suggest more targeted interventions may facilitate prevention and earlier diagnosis in both men and women.

Diagnostic delay and survival in high-grade gliomas - evidence of the 'waiting time paradox'?

INTRODUCTION: We present a retrospective single-centre study to determine whether delays in diagnosis of high-grade glioma (HGG) impact on overall survival (OS). MATERIAL AND METHODS: Consecutive patients diagnosed with HGG at a single neuroscience centre in 2011 were reviewed. Route of referral and time from initial presentation to diagnosis were analysed and correlated with OS. RESULTS: 118 patients were studied - 92 patients with glioblastoma (GBM). Diagnosis of GBM in patients presenting to emergency services was quicker than that through outpatients (8 days vs. 26 days, p < 0.0001), but these patients had significantly worse OS (181 days vs. 386 days p = 0.0075). This trend was observed for the whole cohort (Grade III and GBM), with OS 278 days in patients presenting to emergency services compared with 423 days for patients presenting via outpatients (p = 0.0034). Patients presenting to outpatients were younger (median age: 54 years) compared with patients presenting to emergency services (median age: 62.5 years) (p = 0.0106). There were no other differences between the two groups with respect to the nature of presenting symptoms. CONCLUSION: Earlier diagnosis is paradoxically associated with a worse OS in GBM. An 'aggressive' phenotype with rapid symptomatic deterioration and hence emergency presentation is a poor prognostic factor not influenced by earlier diagnosis.

Age and Referral Route Impact the Access to Diagnosis for Women with Advanced Ovarian Cancer.

Purpose: The majority of women with ovarian cancer are diagnosed in late stages. Most women do have symptoms prior to diagnosis, sometimes several months before the diagnosis. The aim of this study was to evaluate the timeline from the first presentation of symptoms to a physician until there is a reasonable suspicion of cancer, among women diagnosed with advanced stage ovarian cancer. We wanted to investigate which symptoms were the most common and whether there are other factors affecting the time interval before the suspicion of cancer was confirmed. Patients and Methods: This was a retrospective population-based cohort study of women diagnosed with advanced ovarian cancer between January 1, 2017 and December 31, 2019 who were referred to Skane University Hospital Lund, Sweden. Data were collected from electronic medical records at Skane University Hospital. The time interval was recorded as the time from first physician consultation with predefined symptoms to the date when there was a reasonable suspicion of ovarian cancer. Data processing and statistical analysis were performed with the statistical software R. Results: Among the 249 patients included in this study, the median time interval from the first consultation to the reasonable suspicion of cancer was 24 days. The first consultation in specialized care had a 70% decrease in delay compared to primary care. Emergency consultations had a 52.2% decrease in time delay compared to planned consultations. Older age was associated with an increase in the geometric mean by 54.7%, comparing the first to the third quartile. The most common symptom was abdominal pain. Conclusion: The length of time interval from first presentation with symptoms relating to ovarian cancer to reasonable suspicion of cancer was associated with whether the consultation was in primary or specialized care, emergency or planned visit and the patient's age.

Who Presents Where? A Population-Based Analysis of Socio-Demographic Inequalities in Head and Neck Cancer Patients' Referral Routes.

Head and neck cancers (HNC) are often late stage at diagnosis; stage is a major determinant of prognosis. The urgent cancer referral pathway (two week wait; 2WW) within England's National Health Service aims to reduce time to diagnosis. We investigated factors associated with HNC route to diagnosis. Data were obtained from the English population-based cancer registry on 66,411 primary invasive HNCs (ICD C01-14 and C31-32) diagnosed 2006-2014. Multivariable logistic regression determined the likelihood of different diagnosis routes by patients' demographic and clinical characteristics. Significant socio-demographic inequalities were observed. Emergency presentations declined over time and 2WW increased. Significant socio-demographic inequalities were observed. Non-white patients, aged over 65, residing in urban areas with advanced disease, were more likely to have emergency presentations. White males aged 55 and older with an oropharynx cancer were more likely to be diagnosed via 2WW. Higher levels of deprivation were associated with both emergency and 2WW routes. Dental referral was more likely in women, with oral cancers and lower stage disease. Despite the decline over time in emergency presentation and the increased use of 2WW, socio-demographic variation is evident in routes to diagnosis. Further work exploring the reasons for these inequalities, and the consequences for patients' care and outcomes, is urgently required.

Hodgkin lymphoma detection and survival: findings from the Haematological Malignancy Research Network.

BACKGROUND: Hodgkin lymphoma is usually detected in primary care with early signs and symptoms, and is highly treatable with standardised chemotherapy. However, late presentation is associated with poorer outcomes. AIM: To investigate the relationship between markers of advanced disease, emergency admission, and survival following a diagnosis of classical Hodgkin lymphoma (CHL). DESIGN & SETTING: The study was set within a sociodemographically representative UK population-based patient cohort of ~4 million, within which all patients were tracked through their care pathways, and linked to national data obtained from Hospital Episode Statistics (HES) and deaths. METHOD: All 971 patients with CHL newly diagnosed between 1 September 2004-31 August 2015 were followed until 18th December 2018. RESULTS: The median diagnostic age was 41.5 years (range 0-96 years), 55.2% of the patients were male, 31.2% had stage IV disease, 43.0% had a moderate-high or high risk prognostic score, and 18.7% were admitted via the emergency route prior to diagnosis. The relationship between age and emergency admission was U-shaped: more likely in patients aged <25 years and ≥70 years. Compared to patients admitted via other routes, those presenting as an emergency had more advanced disease and poorer 3-year survival (relative survival 68.4% [95% confidence interval {CI} = 60.3 to 75.2] versus 89.8% [95% CI = 87.0 to 92.0], respectively [P<0.01]). However, after adjusting for clinically important prognostic factors, no difference in survival remained. CONCLUSION: These findings suggest that CHL survival as a whole could be increased by around 4% if the cancer in patients who presented as an emergency had been detected at the same point as in other patients.

Time intervals and routes to diagnosis for lung cancer in 10 jurisdictions: cross-sectional study findings from the International Cancer Benchmarking Partnership (ICBP).

OBJECTIVE: Differences in time intervals to diagnosis and treatment between jurisdictions may contribute to previously reported differences in stage at diagnosis and survival. The International Cancer Benchmarking Partnership Module 4 reports the first international comparison of routes to diagnosis and time intervals from symptom onset until treatment start for patients with lung cancer. DESIGN: Newly diagnosed patients with lung cancer, their primary care physicians (PCPs) and cancer treatment specialists (CTSs) were surveyed in Victoria (Australia), Manitoba and Ontario (Canada), Northern Ireland, England, Scotland and Wales (UK), Denmark, Norway and Sweden. Using Wales as the reference jurisdiction, the 50th, 75th and 90th percentiles for intervals were compared using quantile regression adjusted for age, gender and comorbidity. PARTICIPANTS: Consecutive newly diagnosed patients with lung cancer, aged ≥40 years, diagnosed between October 2012 and March 2015 were identified through cancer registries. Of 10 203 eligible symptomatic patients contacted, 2631 (27.5%) responded and 2143 (21.0%) were included in the analysis. Data were also available from 1211 (56.6%) of their PCPs and 643 (37.0%) of their CTS. PRIMARY AND SECONDARY OUTCOME MEASURES: Interval lengths (days; primary), routes to diagnosis and symptoms (secondary). RESULTS: With the exception of Denmark (-49 days), in all other jurisdictions, the median adjusted total interval from symptom onset to treatment, for respondents diagnosed in 2012-2015, was similar to that of Wales (116 days). Denmark had shorter median adjusted primary care interval (-11 days) than Wales (20 days); Sweden had shorter (-20) and Manitoba longer (+40) median adjusted diagnostic intervals compared with Wales (45 days). Denmark (-13), Manitoba (-11), England (-9) and Northern Ireland (-4) had shorter median adjusted treatment intervals than Wales (43 days). The differences were greater for the 10% of patients who waited the longest. Based on overall trends, jurisdictions could be grouped into those with trends of reduced, longer and similar intervals to Wales. The proportion of patients diagnosed following presentation to the PCP ranged from 35% to 75%. CONCLUSION: There are differences between jurisdictions in interval to treatment, which are magnified in patients with lung cancer who wait the longest. The data could help jurisdictions develop more focused lung cancer policy and targeted clinical initiatives. Future analysis will explore if these differences in intervals impact on stage or survival.

Pathways to diagnosis of a second primary cancer: protocol for a mixed-methods systematic review.

INTRODUCTION: As cancer survivors continue to live longer, the incidence of second primary cancers (SPCs) will also rise. Relatively little is understood about the diagnostic pathway for SPCs, how people appraise, interpret symptoms and seek help for a second different cancer and the experiences (including challenges) of healthcare providers relating to SPCs. This study aims to systematically appraise and synthesise the literature on the pathways to diagnosis of an SPC and the associated patient and healthcare provider experiences. METHODS: The approach taken includes systematic searches of published and unpublished literature without any date or language restrictions. MEDLINE, Embase, CAB Abstracts, MEDLINE In-Process and non-indexed citations, PsycINFO, Epub Ahead of Print, In-Process and other non-indexed citations, Ovid MEDLINE Daily, CINAHL, ASSIA, Sociological Abstracts, Web of Science, PROSPERO and grey literature will be searched to identify observational, systematic reviews, mixed methods and qualitative studies of interest. Titles, abstracts and full texts will be screened against the inclusion-exclusion criteria by at least two reviewers independently. Relevant outcomes of interest and study and population characteristics will be extracted. Synthesis will be used guided by the Pathways to Treatment model and the Olesen model of time intervals. ETHICS AND DISSEMINATION: Ethical approval is not required. This systematic review will provide a deeper understanding of the complex and heterogeneous diagnostic pathways of SPCs, while identifying common themes across the diagnostic interval, routes to diagnosis and patient and healthcare provider experiences. These findings will help provide a nuanced picture of the diagnostic pathway for SPCs that may inform policy and consistent practice. In particular, approaches to early diagnosis for an SPC; including the timing and reasons behind the decision by the patient to seek care,the challenges faced by healthcare providers, and in the development of future interventions to reduce the delay in patient time-to-presentation. PROSPERO REGISTRATION NUMBER: CRD42016051692.

Evidence for a delay in diagnosis of Wilms' tumour in the UK compared with Germany: implications for primary care for children.

The UK has a longstanding system of general practice which provides the vast majority of primary care, including that for children. It acts as a 'gatekeeper' to more specialist care. Parents may also use accident and emergency departments as their first point of medical contact for their children. Outcomes in the UK for many conditions in children appear to be worse than in comparable European countries where there is direct access to care by paediatricians. We have therefore looked at pathways to diagnosis and compared outcomes in the childhood kidney cancer, Wilms' tumour, which has been treated in the UK and Germany within the same clinical trial for over a decade. We find that Wilms' tumours are significantly larger in volume and have a more advanced tumour stage at diagnosis in the UK compared to Germany. There is a small (∼3%) difference in event free and overall survival between the two countries. Our data suggest that the system of primary care for children in the UK is less likely to result in the incidental finding of an abdominal mass in a child with no or vague symptoms. This may be a reason for the poorer outcome.

The effect of emergency presentation on surgery and survival in lung cancer patients in England, 2006-2008.

BACKGROUND: A large proportion of lung cancer patients in England are diagnosed through an emergency route, which is associated with poorer outcomes. Here, we investigated the association between emergency presentation and the odds of undergoing surgical resection and subsequent survival among lung cancer patients undergoing surgical resection as well as those who did not. METHODS: Details of 93,783 lung cancers were extracted from the National Cancer Data Repository. For non-small cell lung cancer (NSCLC) patients we calculated odds ratios for undergoing surgical resection. Survival was assessed for resected NSCLC and for all other lung cancer patients in three different time intervals: short-term, intermediate and long-term. RESULTS: Compared with those who did not, NSCLC patients presenting through an emergency route were less likely to undergo surgical resection (adjusted OR=0.22, 95% CI: 0.20-0.24). Patients who underwent surgical resection after an emergency presentation had lower survival in the intermediate period (adjusted HR=1.27, 95% CI: 1.06-1.54) and long term (adjusted HR=1.20, 95% CI: 0.99-1.45). Among all other lung cancer patients, those diagnosed through an emergency route had lower survival, particularly in the short-term (adjusted HR=3.54, 95% CI: 3.42-3.67), but the association remained in the intermediate (adjusted HR=1.66, 95% CI: 1.63-1.69) and long term (adjusted HR=1.10, 95% CI: 1.05-1.15). CONCLUSION: The reduced access to surgical resection and lower survival among lung cancer patients who present through an emergency admission, highlights the importance of ensuring symptoms are recognised early so that presentation as an emergency can be reduced.